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SUMNER, T., L. BURGIN, J. GLOSTER, and S. GUBBINS. "Comparison of pre-emptive and reactive strategies to control an incursion of bluetongue virus serotype 1 to Great Britain by vaccination." Epidemiology and Infection 141, no. 1 (April 4, 2012): 102–14. http://dx.doi.org/10.1017/s0950268812000532.
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SUMMARYBluetongue (BT) is a disease of ruminants caused by bluetongue virus (BTV), which is spread between its hosts by Culicoides midges. Vaccination is the most effective way to protect susceptible animals against BTV and was used reactively to control the recent northern European outbreak. To assess the consequences of using vaccination pre-emptively we used a stochastic, spatially explicit model to compare reactive and pre-emptive vaccination strategies against an incursion of BTV serotype 1 (BTV-1) into Great Britain. Both pre-emptive and reactive vaccination significantly reduced the number of affected farms and limited host morbidity and mortality. In addition, vaccinating prior to the introduction of disease reduced the probability of an outbreak occurring. Of the strategies simulated, widespread reactive vaccination resulted in the lowest levels of morbidity. The predicted effects of vaccination were found to be sensitive to vaccine efficacy but not to the choice of transmission kernel.
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Azman, Andrew S., and Justin Lessler. "Reactive vaccination in the presence of disease hotspots." Proceedings of the Royal Society B: Biological Sciences 282, no. 1798 (January 7, 2015): 20141341. http://dx.doi.org/10.1098/rspb.2014.1341.
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Reactive vaccination has recently been adopted as an outbreak response tool for cholera and other infectious diseases. Owing to the global shortage of oral cholera vaccine, health officials must quickly decide who and where to distribute limited vaccine. Targeted vaccination in transmission hotspots (i.e. areas with high transmission efficiency) may be a potential approach to efficiently allocate vaccine, however its effectiveness will likely be context-dependent. We compared strategies for allocating vaccine across multiple areas with heterogeneous transmission efficiency. We constructed metapopulation models of a cholera-like disease and compared simulated epidemics where: vaccine is targeted at areas of high or low transmission efficiency, where vaccine is distributed across the population, and where no vaccine is used. We find that connectivity between populations, transmission efficiency, vaccination timing and the amount of vaccine available all shape the performance of different allocation strategies. In highly connected settings (e.g. cities) when vaccinating early in the epidemic, targeting limited vaccine at transmission hotspots is often optimal. Once vaccination is delayed, targeting the hotspot is rarely optimal, and strategies that either spread vaccine between areas or those targeted at non-hotspots will avert more cases. Although hotspots may be an intuitive outbreak control target, we show that, in many situations, the hotspot-epidemic proceeds so fast that hotspot-targeted reactive vaccination will prevent relatively few cases, and vaccination shared across areas where transmission can be sustained is often best.
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Calin, Andrei, Nick Goulding, and Dereck Brewerton. "Reactive arthropathy following Salmonella vaccination." Arthritis & Rheumatism 30, no. 10 (October 1987): 1197. http://dx.doi.org/10.1002/art.1780301021.
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Wang, Eric, Alexander A. Cohen, Luis F. Caldera Guzman, Pamela J. Bjorkman, and Arup K. Chakraborty. "Nanoparticle geometry, immune memory, and antigen presentation determine the cross-reactive antibody response against sarbecoviruses." Journal of Immunology 210, no. 1_Supplement (May 1, 2023): 223.01. http://dx.doi.org/10.4049/jimmunol.210.supp.223.01.
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Abstract In response to the threat of emerging SARS-CoV-2 variants and SARS-like betacoronaviruses (sarbecoviruses), mosaic nanoparticles presenting receptor-binding domains (RBDs) of multiple sarbecoviruses have been developed to elicit cross-reactive antibodies that target conserved regions of the RBD. To better understand vaccination with these antigens, we developed a computational model of the humoral response to nanoparticle and spike antigens using a combination of molecular dynamics, Markov processes, and population dynamics simulations. Avidity is currently only accounted for by introducing a second arm on rate, but additional effects of avidity will be considered in the future. Our model agrees with titers measured from nanoparticle and spike vaccinations in animals as well as clinical data from mRNA vaccines. We then used our model to predict the effect of previous vaccinations with wildtype spike on nanoparticle vaccinations. Compared to naïve individuals, previously vaccinated individuals produce a higher cross-reactive titer on the first nanoparticle vaccination and a lower cross-reactive titer on the second. This difference is due to expansion of cross-reactive B cells and competition with strain-specific B cells from previous vaccinations. Furthermore, we find that a cocktail of homotypic nanoparticles produces the same cross-reactive titers as the mosaic nanoparticle, which is because cross-reactive B cells can bind a greater fraction of presented antigen and can survive successive rounds of selection when the nanoparticle density is low. Supported by grants from the National Science Foundation (1745302), NIH (1-R61- AI161805-01), and the Ragon Institute of MGH, MIT, and Harvard.
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Mado, Hubert, Katarzyna Kubicka-Bączyk, and Monika Adamczyk-Sowa. "Anti-severe acute respiratory syndrome coronavirus-2 antibody responses following Pfizer-BioNTech vaccination in a patient with multiple sclerosis treated with ocrelizumab: a case report." Journal of International Medical Research 49, no. 9 (September 2021): 030006052110443. http://dx.doi.org/10.1177/03000605211044378.
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Patients with multiple sclerosis (MS) repeatedly receive therapies that cause B-lymphocyte depletion. This may lead to abnormal immune responses following coronavirus disease 2019 (COVID-19) vaccination, as has been suggested previously. We therefore evaluated post-vaccination immune responses in a patient with MS treated with ocrelizumab. The intervals between ocrelizumab infusions and vaccination were as recommended by the Section of Multiple Sclerosis and Neuroimmunology of the Polish Neurological Society. A reactive immune response was observed in this patient following vaccination. This suggests that appropriate intervals between ocrelizumab infusions and COVID-19 vaccinations may permit the generation of efficacious immune responses in patients receiving B-lymphocyte depleting therapies.
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Milne, George, Joel Kelso, and Heath Kelly. "Strategies for mitigating an influenza pandemic with pre-pandemic H5N1 vaccines." Journal of The Royal Society Interface 7, no. 45 (September 15, 2009): 573–86. http://dx.doi.org/10.1098/rsif.2009.0312.
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The recent worldwide spread of the swine-origin H1N1 2009 influenza outbreak has resulted in its designation as a pandemic by the World Health Organization. While it appears to result in mild symptoms, concern still exists that a more severe influenza pandemic with a high case fatality ratio might arise by reassortment or mutation of the currently circulating avian influenza (H5N1) virus. Given that recently developed candidate pre-pandemic H5N1 vaccines have shown potential for cross-strain protection, we investigated alternative vaccination strategies that exploit such vaccines using an agent-based simulation model of an actual community of approximately 30 000 people in a developed country. Assuming that a two-dose vaccination regimen would be required, we examined three vaccination strategies: pre-emptive, with vaccination applied prior to emergence of human-transmissible H5N1 influenza; reactive, where vaccination was initiated immediately after the first cases in the community were diagnosed; and a ‘split’ strategy where the first dose was administered pre-emptively during the pre-pandemic phase, with the second dose administered reactively. We showed that by effectively moving the delay between first and second doses into the pre-pandemic period, the split vaccination strategy achieved a substantially better attack rate reduction than the reactive strategy. Our results for an influenza strain with a reproduction number of 1.5 suggest reactive vaccination strategies that may be applicable to the current H1N1 2009 pandemic.
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Ho, Tzu-Chuan, Daniel Hueng-Yuan Shen, Chin-Chuan Chang, Hung-Pin Chan, Kuo-Pin Chuang, Cheng-Hui Yuan, Ciao-Ning Chen, Ming-Hui Yang, and Yu-Chang Tyan. "Immune Response Related to Lymphadenopathy Post COVID-19 Vaccination." Vaccines 11, no. 3 (March 17, 2023): 696. http://dx.doi.org/10.3390/vaccines11030696.
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Mass vaccination against coronavirus disease 2019 (COVID-19) is a global health strategy to control the COVID-19 pandemic. With the increasing number of vaccinations, COVID-19 vaccine-associated lymphadenopathy (C19-VAL) has been frequently reported. Current findings emphasize the characteristics of C19-VAL. The mechanism of C19-VAL is complicated to explore. Accumulated reports separately show that C19-VAL incidence is associated with receiver age and gender, reactive change within lymph nodes (LN), etc. We constructed a systematic review to evaluate the associated elements of C19-VAL and provide the mechanism of C19-VAL. Articles were searched from PubMed, Web of Science and EMBASE by using the processing of PRISMA. The search terms included combinations of the COVID-19 vaccine, COVID-19 vaccination and lymphadenopathy. Finally, sixty-two articles have been included in this study. Our results show that days post-vaccination and B cell germinal center response are negatively correlated with C19-VAL incidence. The reactive change within LN is highly related to C19-VAL development. The study results suggested that strong vaccine immune response may contribute to the C19-VAL development and perhaps through the B cell germinal center response post vaccination. From the perspective of imaging interpretation, it is important to carefully distinguish reactive lymph nodes from metastatic lymph node enlargement through medical history collection or evaluation, especially in patients with underlying malignancy.
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Faas, Michel R., Willem A. Mak, Hilde Y. Markus, Ellen M. van der Zwan, Marijke van der Vliet, Johannes G. M. Koeleman, and David S. Y. Ong. "Dynamics of Antibody and T Cell Immunity against SARS-CoV-2 Variants of Concern and the Impact of Booster Vaccinations in Previously Infected and Infection-Naïve Individuals." Vaccines 10, no. 12 (December 13, 2022): 2132. http://dx.doi.org/10.3390/vaccines10122132.
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Despite previous coronavirus disease 2019 (COVID-19) vaccinations and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, SARS-CoV-2 still causes a substantial number of infections due to the waning of immunity and the emergence of new variants. Here, we assessed the SARS-CoV-2 spike subunit 1 (S1)-specific T cell responses, anti-SARS-CoV-2 receptor-binding domain (RBD) IgG serum concentrations, and the neutralizing activity of serum antibodies before and one, four, and seven months after the BNT162b2 or mRNA-1273 booster vaccination in a cohort of previously infected and infection-naïve healthcare workers (HCWs). Additionally, we assessed T cell responses against the spike protein of the SARS-CoV-2 Delta, Omicron BA.1 and BA.2 variants of concern (VOC). We found that S1-specific T cell responses, anti-RBD IgG concentrations, and neutralizing activity significantly increased one month after booster vaccination. Four months after booster vaccination, T cell and antibody responses significantly decreased but levels remained steady thereafter until seven months after booster vaccination. After a similar number of vaccinations, previously infected individuals had significantly higher S1-specific T cell, anti-RBD IgG, and neutralizing IgG responses than infection-naïve HCWs. Strikingly, we observed overall cross-reactive T cell responses against different SARS-CoV-2 VOC in both previously infected and infection-naïve HCWs. In summary, COVID-19 booster vaccinations induce strong T cell and neutralizing antibody responses and the presence of T cell responses against SARS-CoV-2 VOC suggest that vaccine-induced T cell immunity offers cross-reactive protection against different VOC.
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An, Qi-jun, De-an Qin, and Jin-xian Pei. "Reactive arthritis after COVID-19 vaccination." Human Vaccines & Immunotherapeutics 17, no. 9 (May 25, 2021): 2954–56. http://dx.doi.org/10.1080/21645515.2021.1920274.
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Gor, Shivani, Sung-Hee Kim, Khin Yein, Jessica Michael, and Elizabeth Price. "C-Reactive protein rise in rheumatology patients following COVID-19 vaccination." Rheumatology Advances in Practice 7, Supplement_1 (March 24, 2023): i2—i5. http://dx.doi.org/10.1093/rap/rkad005.
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Abstract Objective The aim was to determine the proportion of patients with inflammatory arthritis who have a flare of their rheumatological disease within 4 weeks of receiving a coronavirus disease 2019 (COVID-19) vaccine, using CRP as a surrogate marker. Methods A retrospective review was conducted of notes for patients with inflammatory arthritis within 30 days of their COVID-19 vaccine. An electronic database (DAWN) was used to identify all patients who were currently on a DMARD or biologic therapy. This was then correlated with vaccine data from the National Immunisation and Vaccination System (NIVS) and CRP within 30 days of their vaccination. Results From the DAWN database, 1620 adults were identified (mean age 61 years, 64% female). Three types of vaccinations were administered: AstraZeneca (AZ), BioNTech-Pfizer or Moderna. Vaccine uptake was 1542 of 1620 (95.2% for the first dose), 1550 of 1620 (95.7% for the second dose) and 1437 of 1620 (88.7% for the third dose). One hundred and ninety-two of 1542 patients (12.5%) had a CRP rise of >10 mg/l within 30 days of their vaccine, which was higher than the baseline flare rate of 8.6% (P = 0.0004). Conclusion Patients with inflammatory arthritis and on DMARDs have a high uptake of COVID-19 vaccine (95%), which is greater than the national average. A CRP rise >10 mg/l within 30 days of vaccination was observed in ∼1 in 10 patients in our study population after all three doses. There might be a slight increase in disease flare in patients with inflammatory arthritis after COVID-19 vaccinations, and additional research is required to assess this association further.
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Graham, Carl, Thomas Lechmere, Aisha Rehman, Jeffrey Seow, Ashwini Kurshan, Isabella Huettner, Thomas J. A. Maguire, et al. "The effect of Omicron breakthrough infection and extended BNT162b2 booster dosing on neutralization breadth against SARS-CoV-2 variants of concern." PLOS Pathogens 18, no. 10 (October 3, 2022): e1010882. http://dx.doi.org/10.1371/journal.ppat.1010882.
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COVID-19 vaccines are playing a vital role in controlling the COVID-19 pandemic. As SARS-CoV-2 variants encoding mutations in the surface glycoprotein, Spike, continue to emerge, there is increased need to identify immunogens and vaccination regimens that provide the broadest and most durable immune responses. We compared the magnitude and breadth of the neutralizing antibody response, as well as levels of Spike-reactive memory B cells, in individuals receiving a second dose of BNT126b2 at a short (3–4 week) or extended interval (8–12 weeks) and following a third vaccination approximately 6–8 months later. We show that whilst an extended interval between the first two vaccinations can greatly increase the breadth of the immune response and generate a higher proportion of Spike reactive memory B cells, a third vaccination leads to similar levels between the two groups. Furthermore, we show that the third vaccine dose enhances neutralization activity against omicron lineage members BA.1, BA.2 and BA.4/BA.5 and this is further increased following breakthrough infection during the UK omicron wave. These findings are relevant for vaccination strategies in populations where COVID-19 vaccine coverage remains low.
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Dodd, Roger Y., Edward P. Notari, Jaye P. Brodsky, Gregory A. Foster, Meng Xu, Paula Saá, and Susan L. Stramer. "Patterns of Antibody Response to Severe Acute Respiratory Syndrome Coronavirus 2 Among 1.6 Million Blood Donors: Impact of Vaccination, United States, December 2020–June 2021." Journal of Infectious Diseases 225, no. 1 (October 9, 2021): 5–9. http://dx.doi.org/10.1093/infdis/jiab514.
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Abstract From December 2020 to June 2021, 1654487 blood donors were tested for antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) S1 protein, and 1028547 (62.17%) were reactive. A rapid increase in prevalence was due to vaccination. Among a subset of 1567446 donors, 729771 (46.56%) reported SARS-CoV-2 vaccination, of whom 633769 (86.84%) were S1-antibody reactive only in response to vaccination and 68269 (9.35%) were reactive to both S1 and nucleocapsid in response to prior infection; the remainder were not reactive to either antibody. Among the 837675 (53.44%) donors who did not report vaccination, 210022 (25.07%) had reactivity to both antibodies and 29446 (3.52%) to S1 only.
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Yole, D. S., R. Pemberton, G. D. F. Reid, and R. A. Wilson. "Protective immunity toSchistosoma mansoniinduced in the olive baboonPapio anubisby the irradiated cercaria vaccine." Parasitology 112, no. 1 (January 1996): 37–46. http://dx.doi.org/10.1017/s0031182000065057.
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SUMMARYThe radiation-attenuated schistosome vaccine induces a high level of protective immunity in rodents. In order to assess its potential relevance to man, we have tested its efficacy in the non-human primatePapio anubis. A vaccination regime consisting of 3 exposures of approximately 9000 cercariae irradiated with 30 or 60krad. of gamma radiation induced > 50% protection to a challenge with normal larvae. A lower attenuating dose of 20 krad., optimal for vaccination of mice, was less effective. All vaccination regimes elicited a population of PBMC which proliferatedin vitroin response to antigen. These responses peaked after the third exposure but were significantly lower after challenge. They revealed relatively little cross-reactivity with adultSchistosoma haematobiumantigens and provided some evidence for stage-specific antigens. Circulating IgM reactive with adultS. mansoniantigen was detected after the second vaccination but levels remained low throughout. In contrast, IgG levels were boosted by successive vaccinations, although they showed a tendency to decline from 14 days after each exposure. There also appeared to be a lag of about 14 days after challenge before levels began to rise. Thus, both proliferation and antibody data suggest a lower responsiveness after challenge which may reflect either the reduced antigenic load or immunogenicity of normal, compared to vaccinating larvae. The data indicate that the attenuated schistosome vaccine is capable of inducing protection in a highly permissive primate host, with the implication that the mechanisms involved may also be relevant to man.
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Williams, Erin, Devin J. Kennedy, Michael Hoffer, Juan Manuel Carreño, Florian Krammer, Suresh Pallikkuth, and Savita Pahwa. "Chronic False Positive Rapid Plasma Reagin (RPR) Tests Induced by COVID-19 Vaccination." COVID 3, no. 9 (August 30, 2023): 1304–9. http://dx.doi.org/10.3390/covid3090090.
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False positive reactive plasmin reagin (RPR) reactivity following a COVID-19 vaccine has been reported, and it is therefore conceivable that individuals who receive frequent coronavirus disease 2019 (COVID-19) vaccinations may exhibit durable RPR responses. Here, we sought to investigate the extent to which repeated mRNA COVID-19 vaccines can elicit chronic false RPR reactivity in a longitudinal cohort. Participants (n = 119) in an IRB-approved (#20201026), longitudinal SARS-CoV-2 cohort study were screened for RPR reactivity via manual RPR card assays. Samples with reactive results underwent additional testing, including follow-on RPR screening at additional timepoints, confirmatory fluorescent treponemal antibody (FTA-ABS) testing and anti-nuclear antibody (ANA) testing. Medical histories were collected. We observed (n = 2) screen-positive RPR results (1.7% [2/119]) following booster vaccination, for which two individuals exhibited chronic, vaccine-induced RPR reactivity for up to 9 months following booster vaccination. Both participants were ANA-negative. It is imperative for clinicians to be mindful of the potential immunologic interference of COVID-19 vaccines with standard infectious disease assays, including RPR testing. Detailed medical histories and clinical contexts, including recent vaccination, should be reviewed prior to proceeding with distressing and invasive workups.
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Sinha, Surabhi, Diksha Agrawal, Srishti Dabas, and Purnima Malhotra. "Reactive arthritis following vaccination against COVID-19: An unexpected adverse reaction." Indian Dermatology Online Journal 14, no. 3 (2023): 424. http://dx.doi.org/10.4103/idoj.idoj_338_22.
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Tani, Yuta, Morihito Takita, Yurie Kobashi, Masatoshi Wakui, Tianchen Zhao, Chika Yamamoto, Hiroaki Saito, et al. "Varying Cellular Immune Response against SARS-CoV-2 after the Booster Vaccination: A Cohort Study from Fukushima Vaccination Community Survey, Japan." Vaccines 11, no. 5 (April 29, 2023): 920. http://dx.doi.org/10.3390/vaccines11050920.
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Booster vaccination reduces the incidence of severe cases and mortality related to COVID-19, with cellular immunity playing an important role. However, little is known about the proportion of the population that has achieved cellular immunity after booster vaccination. Thus, we conducted a Fukushima cohort database and assessed humoral and cellular immunity in 2526 residents and healthcare workers in Fukushima Prefecture in Japan through continuous blood collection every 3 months from September 2021. We identified the proportion of people with induced cellular immunity after booster vaccination using the T-SPOT.COVID test, and analyzed their background characteristics. Among 1089 participants, 64.3% (700/1089) had reactive cellular immunity after booster vaccination. Multivariable analysis revealed the following independent predictors of reactive cellular immunity: age < 40 years (adjusted odds ratio: 1.81; 95% confidence interval: 1.19–2.75; p-value: 0.005) and adverse reactions after vaccination (1.92, 1.19–3.09, 0.007). Notably, despite IgG(S) and neutralizing antibody titers of ≥500 AU/mL, 33.9% (349/1031) and 33.5% (341/1017) of participants, respectively, did not have reactive cellular immunity. In summary, this is the first study to evaluate cellular immunity at the population level after booster vaccination using the T-SPOT.COVID test, albeit with several limitations. Future studies will need to evaluate previously infected subjects and their T-cell subsets.
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Ciglenecki, Iza, John Rumunu, Joseph F. Wamala, Patrick Nkemenang, Jetske Duncker, Robin Nesbitt, Etienne Gignoux, et al. "The first reactive vaccination campaign against hepatitis E." Lancet Infectious Diseases 22, no. 8 (August 2022): 1110–11. http://dx.doi.org/10.1016/s1473-3099(22)00421-2.
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Sahin, Nilay, Ali Salli, Ayse Unal Enginar, and Hatice Ugurlu. "Reactive arthritis following tetanus vaccination: a case report." Modern Rheumatology 19, no. 2 (April 2009): 209–11. http://dx.doi.org/10.3109/s10165-008-0140-2.
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Biasi, D., A. Carletto, P. Caramaschi, M. Tonoli, and L. M. Bambara. "A case of reactive arthritis after influenza vaccination." Clinical Rheumatology 13, no. 4 (December 1994): 645. http://dx.doi.org/10.1007/bf02243011.
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Barros, Teresa, Gabriel Moran, and Benjamin Uberti. "Reactive Seizures After Vaccination in a Thoroughbred Broodmare." Journal of Equine Veterinary Science 73 (February 2019): 106–9. http://dx.doi.org/10.1016/j.jevs.2018.12.004.
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Kohrt, Holbrook E., Antonia MS Mueller, Jeanette B. Baker, Matthew J. Goldstein, Evan Newell, Suparna Dutt, Debra K. Czerwinski, Robert Lowsky, and Samuel Strober. "Donor Immunization with WT1 Peptide Augments Anti-Leukemic Activity After MHC-Matched Bone Marrow Transplantation." Blood 118, no. 21 (November 18, 2011): 1896. http://dx.doi.org/10.1182/blood.v118.21.1896.1896.
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Abstract Abstract 1896 The curative potential of MHC-matched allogeneic bone marrow transplantation (BMT) is in part due to immunologic graft-versus-tumor (GvT) reactions mediated by donor T cells that recognize host minor histocompatibility antigens. Immunization with leukemia-associated antigens, such as Wilm's Tumor 1 (WT1) peptides, induces a T cell population that is tumor antigen specific. We determined whether BMT combined with immunotherapy using WT1 peptide vaccination of donors induced more potent anti-tumor activity when combined with allotransplantation. WT1 peptide vaccinations of healthy syngeneic or allogeneic donor mice with a 9-mer WT1 peptide (amino acids 126–134, the WT1 9-mer which has the highest binding affinity for H-2Db) and Incomplete Freund's Adjuvant induced CD8+ T cells that were specifically reactive to WT1-expressing FBL3 leukemia cells. We found that compared to vaccination with IFA alone, four weekly WT1 vaccinations induced an increased percentage of WT1-tetramer+CD8 T-cells (0.15% vs. 1%) in the peripheral blood 28 days following the first vaccination (Figure A *p<.001). CD8 T-cells producing IFN-γ+ after co-culture with tumor cells were similarly increased (0.11% vs. 13.6%) at this timepoint (Figure B *p<.001). They were CD44hi suggesting a memory phenotype, specifically reactive to WT1-expressing tumor (FBL3 and not H11), and increased in a vaccination dose-dependent fashion (Figure A and B). Four weekly WT1 vaccinations prevented tumor growth in donors following intravenous leukemia challenge. In contrast, in tumor-bearing mice, WT1 vaccinations failed to induce WT1-tetramer+ or IFN-γ+ CD8 T-cells and were ineffective as a therapeutic vaccine based on intensity of bioluminescence from luciferase-labeled FBL3 leukemia and mortality. BMT from WT1 vaccinated MHC-matched donors including LP/J and C3H.SW, but not C57BL/6 syngeneic donors, into C57BL/6 recipient tumor-bearing mice was effective as a therapeutic maneuver and resulted in eradication of luciferase-labeled FBL3 leukemia and survival of 70–90% of mice. Interestingly, the transfer of total CD8+ T cells from immunized donors was more effective than the transfer of WT1-tetramer+CD8+ T cells, likely as a result of alloreactive and tumor-antigen reactive T cells contained with the donor total CD8+ T cells. Total and tetramer+CD8+ T cells required CD4+ T cell help for maximal anti-tumor activity, which was equivalent in efficacy from immunized or unimmunized CD4+ T cell donors. Total CD4+ T cells, alone, from immunized donors provided no anti-tumor activity. The infused donor LP/J or C3H.SW CD8+ T cells collected from cured C57BL/6 recipients, were highly reactive against WT1-expressing FBL3 leukemia cells (14% IFN-γ+) compared to non-WT1-expressing H11 leukemia cells (5% IFN-γ+). The circulating, WT1-tetramer+CD8+ T cell population expanded in cured recipients, peaking at 3.5% on day 50 and contracting through day 100 post-BMT to 0.56%. These findings show that peptide vaccination of donor mice with a tumor antigen dramatically enhances GvT activity and is synergistic with allogeneic BMT. This novel and broadly applicable approach, using leukemia-associated antigen immunization to enhance GvT by creating an “educated” donor T cell graft for allogeneic transplantation of patients with acute myeloid leukemia and myelodysplastic syndrome, is currently being translated to a Phase 1 clinical trial at our institution. Disclosures: No relevant conflicts of interest to declare.
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Chen, Yuezhou, Youyi Wang, Yuanhao Hu, Nuo Gong, Yunfeng Li, Jiayi Huang, Jiaxin He, and Shun Huang. "Recall of cross-reactive memory B cells enhances antibody durability and breadth against SARS-CoV-2 variants." Journal of Immunology 212, no. 1_Supplement (May 1, 2024): 0141_4393. http://dx.doi.org/10.4049/jimmunol.212.supp.0141.4393.
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Abstract Long-lasting antibody production with broad recognition breadth is crucial to combat with many pathogens. After infection or vaccination, B cell memory is preserved via two key elements: memory B cells, which can be efficiently recalled during subsequent encounters, and long-lived plasma cells, which continue to produce antibodies over the long term. It's critical to understand antibody durability and how memory can identify different viral variants following iterative exposures. We examined the recognition of SARS-CoV-2 variants, the dynamics of memory B cells, and the secretion of antibodies over time after recurrent infections and vaccinations. Within unvaccinated individuals who recovered from COVID, enhanced antibody stability over time was observed within a subgroup of individuals who recovered more quickly from COVID, had greater percentage of spike specific memory circulating T follicular helper (cTfh), and harbored significantly more memory B cells cross-reactive to endemic coronaviruses early after infection. These cross-reactive clones map to the conserved S2 region of SARS-CoV-2 spike with higher somatic hypermutation levels and affinity. Following SARS-CoV-2 inactivated vaccination, frequency of cross-reactive memory B cells after BF.7 infection links to antibody longevity and neutralization breadth to SARS-CoV-2 variants. We conclude that memory B cell recall shapes functional cross-variant antibody repertoire composition and longevity.
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Dale, C. J., R. De Rose, I. Stratov, S. Chea, D. C. Montefiori, S. Thomson, I. A. Ramshaw, et al. "Efficacy of DNA and Fowlpox Virus Priming/Boosting Vaccines for Simian/Human Immunodeficiency Virus." Journal of Virology 78, no. 24 (December 15, 2004): 13819–28. http://dx.doi.org/10.1128/jvi.78.24.13819-13828.2004.
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ABSTRACT Further advances are required in understanding protection from AIDS by T-cell immunity. We analyzed a set of multigenic simian/human immunodeficiency virus (SHIV) DNA and fowlpox virus priming and boosting vaccines for immunogenicity and protective efficacy in outbred pigtail macaques. The number of vaccinations required, the effect of DNA vaccination alone, and the effect of cytokine (gamma interferon) coexpression by the fowlpox virus boost was also studied. A coordinated induction of high levels of broadly reactive CD4 and CD8 T-cell immune responses was induced by sequential DNA and fowlpox virus vaccination. The immunogenicity of regimens utilizing fowlpox virus coexpressing gamma interferon, a single DNA priming vaccination, or DNA vaccines alone was inferior. Significant control of a virulent SHIV challenge was observed despite a loss of SHIV-specific proliferating T cells. The outcome of challenge with virulent SHIVmn229 correlated with vaccine immunogenicity except that DNA vaccination alone primed for protection almost as effectively as the DNA/fowlpox virus regimen despite negligible immunogenicity by standard assays. These studies suggest that priming of immunity with DNA and fowlpox virus vaccines could delay AIDS in humans.
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Pedachenko, Y. E., I. G. Vasilieva, N. G. Chopik, O. I. Tsiubko, N. P. Oleksenko, A. B. Dmytrenko, T. A. Makarova, and I. M. Shub. "Molecular Characteristics of Blood Serum After Covid-19 Vaccination in a Remote Period." Mikrobiolohichnyi Zhurnal 86, no. 2 (April 28, 2024): 75–89. http://dx.doi.org/10.15407/microbiolj86.02.075.
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COVID-19 is a dangerous disease with long-lasting consequences. Vaccination contributes to the accumulation of neutralizing anti-S IgG antibodies, reducing the incidence of COVID-19 and its complications. However, in some individuals, the inflammatory process can persist for an indefinite period and lead to a wide range of dysfunctions. The current task is to investigate molecular markers for their detection. The aim of this study is to examine the levels of anti-S IgG antibodies, lactate, glucose, lactate dehydrogenase, and C-reactive protein in the peripheral blood of individuals who have and have not been affected by COVID-19 after vaccination. The research subject is venous blood. Among 547 employees of the Neurosurgery Institute (481 vaccinated against COVID-19 and 66 unvaccinated individuals), levels of anti-S IgG antibodies were investigated, as well as levels of lactate, lactate dehydrogenase, glucose, and C-reactive protein. At the time of the study, among 372 individuals, 16 months had passed from the first vaccination, and 12 months had passed from the second vaccination; in 21 individuals, 12 months had passed after a single vaccination, and in 88 individuals, 16 months had passed from the first vaccination, 12 months from the second, and 6 months from the third vaccination. Methods. Quantitative determination of IgG antibodies to the S protein of the SARS-CoV-2 virus. Confirmation of COVID-19 using the RT-PCR method (Allplex 2019-nCoV kit, SeeGene, Korea). Levels of lactate, lactate dehydrogenase, glucose, and C-reactive protein were determined using reagents from BioSystems (Spain). Statistical analysis of the obtained data was performed using Jamovi software (USA) and the following criteria: χ2 ‒ Kruskal-Wallis, W ‒ Dwass-Steel-Critchlow-Fligner (DSCF), χ2 ‒ Pearson, t ‒ Student, rs ‒ Spearman, τb ‒ Kendall. A statistically significant difference was considered at p < 0.05. Results. The level of anti-S IgG antibodies to the SARS-CoV-2 virus was higher in vaccinated individuals compared to unvaccinated individuals (Kruskal-Wallis χ2=14.09; p < 0.001). A higher level of antibodies to the S protein of the virus was observed when using the Comirnaty vaccine compared to vaccination with Moderna, AstraZeneca, Pfizer, and CoronaVac (Dwass-Steel-Critchlow-Fligner (DSCF): W 4.26, p=0.002; W 4.62, p=0.010; W 4.84, p=0.006, respectively). Vaccination reduces the likelihood of contracting the disease by 1.84 times (Odds Ratio (OR) 1.84; 95% Confidence Interval (CI) 1.02‒3.30; χ2=4.129; p=0.043). However, no statistically significant dependence on the prevention of COVID-19 incidence based on the type of vaccines used was found (Kruskal-Wallis χ2=2.072; p=0.72). A statistically significant difference in C-reactive protein levels is observed between groups with early mild complications and early moderate-severity complications (DSCF: W=4.193, p=0.009). A statistically significant difference in LDH levels is noted between individuals without chronic diseases and those with chronic diseases at the time of the study (Kruskal-Wallis χ2=6.08, p=0.014). In individuals vaccinated against the SARS-CoV-2 virus, a positive correlation is found between the levels of C-reactive protein and lactate dehydrogenase (Kendall's τb 0.134, p < 0.001). The mean levels of lactate among individuals with mild, moderate, and severe forms of COVID-19 are higher than the reference mean; similarly, the mean levels of glucose in these same groups are higher than the reference mean. A positive correlation exists between the levels of lactate and glucose among individuals vaccinated against the SARS-CoV-2 virus (Kendall's τb 0.082, p < 0.01). Conclusions. Vaccination contributes to an increase in antibody levels. The level of antibodies after the third vaccination exceeded the levels after the first (Dwass-Steel-Critchlow-Fligner (DSCF): W 4.42, p=0.005) and second vaccinations (W 4.24, p=0.008). Vaccination reduces the likelihood of COVID-19 infection by 1.84 times (Odds Ratio ‒ 1.84; 95% Confidence Interval 1.02‒3.30; Pearson χ2=4.129; p=0.043). The frequency of COVID-19 incidence is not dependent on the type of vaccine used: AstraZeneca, Comirnaty, CoronaVac, Moderna, Pfizer (Kruskal-Wallis χ2=2.072; p=0.723), and the level of antibodies in the vaccinated individuals' serum. In the post-COVID-19 remote period, regardless of vaccination status, various complications are observed. However, among the vaccinated, the number of individuals without complications or with minimal complications is greater than in the unvaccinated group, while the number of individuals with early and severe complications is lower (Kruskal-Wallis χ2=6.127; p=0.047). A high level of C-reactive protein (DSCF: W=4.19, p=0.009), a tendency toward increased levels of lactate dehydrogenase (DSCF: W=3.27, p=0.054), elevated levels of lactate (2.17+1.23, t=3.34; p=0.002), and glucose (6.06+0.048, t=10.54; p < 0.001) indicate that after recovering from COVID-19, regardless the type of vaccines used, in individuals with distant symptoms there are metabolic changes that are signs of a chronic inflammatory process. Individuals with chronic diseasees show an increase in the level of lactate dehydrogenase (χ2=6.08; p=0.014) and a tendency toward increased levels of C-reactive protein (χ2=3.74; p=0.053). Molecular markers of inflammation such as increased levels of lactate, glucose, C-reactive protein, and lactate dehydrogenase are informative for identifying individuals with an inflammatory process in the post-COVID-19 remote period.
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Qi, Qian, Mary M. Cavanagh, Sabine Le Saux, Hong NamKoong, Chulwoo Kim, Emerson Turgano, Yi Liu, et al. "Diversification of the antigen-specific T cell receptor repertoire after varicella zoster vaccination." Science Translational Medicine 8, no. 332 (March 30, 2016): 332ra46. http://dx.doi.org/10.1126/scitranslmed.aaf1725.
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Diversity and size of the antigen-specific T cell receptor (TCR) repertoire are two critical determinants for successful control of chronic infection. Varicella zoster virus (VZV) that establishes latency during childhood can escape control mechanisms, in particular with increasing age. We examined the TCR diversity of VZV-reactive CD4 T cells in individuals older than 50 years by studying three identical twin pairs and three unrelated individuals before and after vaccination with live attenuated VZV. Although all individuals had a small number of dominant T cell clones, the breadth of the VZV-specific repertoire differed markedly. A genetic influence was seen for the sharing of individual TCR sequences from antigen-reactive cells but not for repertoire richness or the selection of dominant clones. VZV vaccination favored the expansion of infrequent VZV antigen–reactive TCRs, including those from naïve T cells with lesser boosting of dominant T cell clones. Thus, vaccination does not reinforce the in vivo selection that occurred during chronic infection but leads to a diversification of the VZV-reactive T cell repertoire. However, a single-booster immunization seems insufficient to establish new clonal dominance. Our results suggest that repertoire analysis of antigen-specific TCRs can be an important readout to assess whether a vaccination was able to generate memory cells in clonal sizes that are necessary for immune protection.
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Bita Fouda, Andre Arsene, Anderson Latt, Abdoulaye Sinayoko, Franck Fortune Roland Mboussou, Lorenzo Pezzoli, Katya Fernandez, Clement Lingani, et al. "The Bacterial Meningitis Epidemic in Banalia in the Democratic Republic of Congo in 2021." Vaccines 12, no. 5 (April 25, 2024): 461. http://dx.doi.org/10.3390/vaccines12050461.
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Background: The Banalia health zone in the Democratic Republic of Congo reported a meningitis epidemic in 2021 that evolved outside the epidemic season. We assessed the effects of the meningitis epidemic response. Methods: The standard case definition was used to identify cases. Care was provided to 2651 in-patients, with 8% of them laboratory tested, and reactive vaccination was conducted. To assess the effects of reactive vaccination and treatment with ceftriaxone, a statistical analysis was performed. Results: Overall, 2662 suspected cases of meningitis with 205 deaths were reported. The highest number of cases occurred in the 30–39 years age group (927; 38.5%). Ceftriaxone contributed to preventing deaths with a case fatality rate that decreased from 70.4% before to 7.7% after ceftriaxone was introduced (p = 0.001). Neisseria meningitidis W was isolated, accounting for 47/57 (82%), of which 92% of the strains belonged to the clonal complex 11. Reactive vaccination of individuals in Banalia aged 1–19 years with a meningococcal multivalent conjugate (ACWY) vaccine (Menactra®) coverage of 104.6% resulted in an 82% decline in suspected meningitis cases (incidence rate ratio, 0.18; 95% confidence interval, 0.02–0.80; p = 0.041). Conclusion: Despite late detection (two months) and reactive vaccination four months after crossing the epidemic threshold, interventions implemented in Banalia contributed to the control of the epidemic.
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Diego, Juan García-Bernalt, Gagandeep Singh, Sonia Jangra, Kim Handrejk, Manon Laporte, Lauren A. Chang, Sara S. El Zahed, et al. "Breakthrough infections by SARS-CoV-2 variants boost cross-reactive hybrid immune responses in mRNA-vaccinated Golden Syrian hamsters." PLOS Pathogens 20, no. 1 (January 10, 2024): e1011805. http://dx.doi.org/10.1371/journal.ppat.1011805.
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Hybrid immunity (vaccination + natural infection) to SARS-CoV-2 provides superior protection to re-infection. We performed immune profiling studies during breakthrough infections in mRNA-vaccinated hamsters to evaluate hybrid immunity induction. The mRNA vaccine, BNT162b2, was dosed to induce binding antibody titers against ancestral spike, but inefficient serum virus neutralization of ancestral SARS-CoV-2 or variants of concern (VoCs). Vaccination reduced morbidity and controlled lung virus titers for ancestral virus and Alpha but allowed breakthrough infections in Beta, Delta and Mu-challenged hamsters. Vaccination primed for T cell responses that were boosted by infection. Infection back-boosted neutralizing antibody responses against ancestral virus and VoCs. Hybrid immunity resulted in more cross-reactive sera, reflected by smaller antigenic cartography distances. Transcriptomics post-infection reflects both vaccination status and disease course and suggests a role for interstitial macrophages in vaccine-mediated protection. Therefore, protection by vaccination, even in the absence of high titers of neutralizing antibodies in the serum, correlates with recall of broadly reactive B- and T-cell responses.
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Silva, Eloia Emanuelly Dias, Marina dos Santos Barreto, Ronaldy Santana Santos, Deise Maria Rego Rodrigues Silva, Pedro Henrique Macedo Moura, Pamela Chaves de Jesus, Jessiane Bispo de Souza, Adriana Gibara Guimarães, Lucas Alves da Mota Santana, and Lysandro Pinto Borges. "The Role of COVID-19 Vaccination in Serological and Infectious Response in the Xokós Indigenous Community." COVID 4, no. 9 (September 16, 2024): 1476–84. http://dx.doi.org/10.3390/covid4090104.
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Objectives: This study aims to examine the serological and infectious characteristics of the Xokós indigenous community in Brazil, both prior to and following COVID-19 immunization; Methods: Immunofluorescence assays were employed to identify the SARS-CoV-2 viral antigen, while IgM and IgG antibody tests for COVID-19 were utilized to assess the participants’ infectious and serological profiles in July 2020, before the commencement of the COVID-19 vaccination campaign, and in March 2022, during the booster dose vaccination campaign; Results: The majority of participants (n = 22) were female, with an average age of 42.20 years. The most prevalent comorbidity was hypertension (60%; n = 9), followed by hypertension associated with diabetes (20%; n = 3). No statistically significant correlation was found between the timing of vaccination and the levels of antigens or IgM. However, the prevalence of reactive antigens and IgM was 13.3% (n = 4) in the pre-vaccination group and 3.3% (n = 1) in the post-vaccination group. A statistically significant difference in IgG production was observed before and after vaccination (χ2(1) = 39.095, p < 0.01), as well as differences in IgG antibody detection before and after vaccination and in the vaccines used. Participants showed a higher probability of reactive IgG antibodies following vaccination; Conclusions: Our data demonstrate the beneficial effects of vaccination on the indigenous community, highlighting that continued immunization is a crucial step in protecting indigenous health and preventing severe outbreaks and deaths associated with the disease.
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Honfi, Dániel, Nikolett Gémes, Enikő Szabó, Patrícia Neuperger, József Á. Balog, Lajos I. Nagy, Gergely Toldi, László G. Puskás, Gábor J. Szebeni, and Attila Balog. "Comparison of Homologous and Heterologous Booster SARS-CoV-2 Vaccination in Autoimmune Rheumatic and Musculoskeletal Patients." International Journal of Molecular Sciences 23, no. 19 (September 27, 2022): 11411. http://dx.doi.org/10.3390/ijms231911411.
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Vaccination against SARS-CoV-2 to prevent COVID-19 is highly recommended for immunocompromised patients with autoimmune rheumatic and musculoskeletal diseases (aiRMDs). Little is known about the effect of booster vaccination or infection followed by previously completed two-dose vaccination in aiRMDs. We determined neutralizing anti-SARS-CoV-2 antibody levels and applied flow cytometric immunophenotyping to quantify the SARS-CoV-2 reactive B- and T-cell mediated immunity in aiRMDs receiving homologous or heterologous boosters or acquired infection following vaccination. Patients receiving a heterologous booster had a higher proportion of IgM+ SARS-CoV-2 S+ CD19+CD27+ peripheral memory B-cells in comparison to those who acquired infection. Biologic therapy decreased the number of S+CD19+; S+CD19+CD27+IgG+; and S+CD19+CD27+IgM+ B-cells. The response rate to a booster event in cellular immunity was the highest in the S-, M-, and N-reactive CD4+CD40L+ T-cell subset. Patients with a disease duration of more than 10 years had higher proportions of CD8+TNF-α+ and CD8+IFN-γ+ T-cells in comparison to patients who were diagnosed less than 10 years ago. We detected neutralizing antibodies, S+ reactive peripheral memory B-cells, and five S-, M-, and N-reactive T-cells subsets in our patient cohort showing the importance of booster events. Biologic therapy and <10 years disease duration may confound anti-SARS-CoV-2 specific immunity in aiRMDs.
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Rosenblat, Todd L., Mark G. Frattini, Suzanne M. Chanel, Tao Dao, Yvette Bernal, Joseph G. Jurcic, Rhong Zhang, et al. "Phase II Trial of WT1 Analog Peptide Vaccine in Patients with Acute Myeloid Leukemia (AML) in Complete Remission (CR)." Blood 120, no. 21 (November 16, 2012): 3624. http://dx.doi.org/10.1182/blood.v120.21.3624.3624.
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Abstract Abstract 3624 WT1 is a transcription factor which has been implicated in leukemogenesis and has been used as a marker of minimal residual disease (MRD). We previously demonstrated the feasibility of vaccinating AML patients in CR with a multivalent WT1 peptide vaccine and inducing immune responses. In an effort to further explore the safety and efficacy of this approach, we are conducting a Phase II study in which the vaccine is administered to AML patients in first CR and who completed all planned postremission chemotherapy. Eligible patients had WT1 transcript detectable by RT-PCR. The vaccine consisted of 4 native and derived WT1 peptides administered with the immune adjuvants Montanide and GM-CSF. Patients received 6 vaccinations over 10 weeks. Early toxicity was assessed at weeks 2 and 4. Immune responses were evaluated at week 12 by CD4+ T cell proliferation, CD3+ T cell interferon-g interferon release (ELISPOT) and WT1 peptide tetramer staining. Patients who were clinically stable and without disease recurrence could continue with up to 6 more vaccinations administered approximately every month. To date, 12 patients have been accrued to the study (6-M, 6-F; median age – 66 years, range 26–73 years). Cytogenetic subtypes varied among the study patients (Favorable-3, Intermediate-5, Unfavorable-4). The median time to vaccination after achieving CR was 7.5 months (range: 3–22 months). One patient was removed early because of relapse prior to receiving the first vaccination. Four patients have received at least 6 vaccines and 2 others have completed 12 vaccinations. Eight patients are alive without evidence of disease. One of these patients has an HLA-A02 subtype and was found to have developed T cells reactive with WT1-A (native peptide) HLA tetramers following 6 vaccinations which persisted (at a lower level) until after the 12th vaccination. Three patients relapsed during vaccination (after 1, 5 and 11 vaccines) and 2 of the 3 have died. Two of the relapsed patients who had sample available for immunologic evaluation, did not develop a CD4+ response to any of the peptides tested. Two other patients discontinued vaccination because of toxicity (hypersensitivity/pain with GM-CSF administration). Both remain in CR. No episodes of anaphylaxis or generalized urticaria were observed. Neither median disease free survival nor overall survival has been reached in this small cohort of patients. These preliminary findings demonstrate that the WT1 peptide vaccine is relatively well tolerated and has immunologic activity. Trial accrual is ongoing and further follow-up is required before any beneficial effect on outcome can be determined. Disclosures: Scheinberg: Formula Pharma: WT1 Vaccine inventor, Patent held by MSKCC and Licensed to Formula Pharma, WT1 Vaccine inventor, Patent held by MSKCC and Licensed to Formula Pharma Patents & Royalties.
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Asakawa, Junichi, Shigeto Kobayashi, Kazuhiko Kaneda, Hitoshi Ogasawara, Masahiro Sugawara, Masahiko Yasuda, and Hiroshi Hashimoto. "Reactive arthritis after influenza vaccination: report of a case." Modern Rheumatology 15, no. 4 (August 2005): 283–85. http://dx.doi.org/10.3109/s10165-005-0399-5.
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Kohrt, Holbrook E., Antonia Müller, Jeanette Baker, Matthew J. Goldstein, Evan Newell, Suparna Dutt, Debra Czerwinski, Robert Lowsky, and Samuel Strober. "Donor immunization with WT1 peptide augments antileukemic activity after MHC-matched bone marrow transplantation." Blood 118, no. 19 (November 10, 2011): 5319–29. http://dx.doi.org/10.1182/blood-2011-05-356238.
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Abstract The curative potential of MHC-matched allogeneic bone marrow transplantation (BMT) is in part because of immunologic graft-versus-tumor (GvT) reactions mediated by donor T cells that recognize host minor histocompatibility antigens. Immunization with leukemia-associated antigens, such as Wilms Tumor 1 (WT1) peptides, induces a T-cell population that is tumor antigen specific. We determined whether allogeneic BMT combined with immunotherapy using WT1 peptide vaccination of donors induced more potent antitumor activity than either therapy alone. WT1 peptide vaccinations of healthy donor mice induced CD8+ T cells that were specifically reactive to WT1-expressing FBL3 leukemia cells. We found that peptide immunization was effective as a prophylactic vaccination before tumor challenge, yet was ineffective as a therapeutic vaccination in tumor-bearing mice. BMT from vaccinated healthy MHC-matched donors, but not syngeneic donors, into recipient tumor-bearing mice was effective as a therapeutic maneuver and resulted in eradication of FBL3 leukemia. The transfer of total CD8+ T cells from immunized donors was more effective than the transfer of WT1-tetramer+CD8+ T cells and both required CD4+ T-cell help for maximal antitumor activity. These findings show that WT1 peptide vaccination of donor mice can dramatically enhance GvT activity after MHC-matched allogeneic BMT.
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Gerges, Daniela, Sebastian Kapps, Esperanza Hernández-Carralero, Raimundo Freire, Monika Aiad, Sophie Schmidt, Wolfgang Winnicki, et al. "Vaccination with BNT162b2 and ChAdOx1 nCoV-19 Induces Cross-Reactive Anti-RBD IgG against SARS-CoV-2 Variants including Omicron." Viruses 14, no. 6 (May 28, 2022): 1181. http://dx.doi.org/10.3390/v14061181.
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SARS-CoV-2 variants of concern (VOCs) have caused a significant increase in infections worldwide. Despite high vaccination rates in industrialized countries, the fourth VOC, Omicron, has outpaced the Delta variant and is causing breakthrough infections in individuals with two booster vaccinations. While the magnitude of morbidity and lethality is lower in Omicron, the infection rate and global spread are rapid. Using a specific IgG multipanel-ELISA with the spike protein’s receptor-binding domain (RBD) from recombinant Alpha, Gamma, Delta, and Omicron variants, sera from health-care workers from the Medical University of Vienna were tested pre-pandemic and post-vaccination (BNT162b2; ChAdOx1 nCoV-19). The cohort was continuously monitored by SARS-CoV-2 testing and commercial nucleocapsid IgG ELISA. RBD IgG ELISA showed significantly lower reactivity against the Omicron-RBD compared to the Alpha variant in all individuals (p < 0.001). IgG levels were independent of sex, but were significantly higher in BNT162b2 recipients <45 years of age for Alpha, Gamma, and Delta (p < 0.001; p = 0.040; p = 0.004, respectively). Pre-pandemic cross-reactive anti-Omicron IgG was detected in 31 individuals and was increased 8.78-fold after vaccination, regardless of vaccine type. The low anti-RBD Omicron IgG level could explain the breakthrough infections and their presence could also contribute to a milder COVID-19 course by cross-reactivity and broadening the adaptive immunity.
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Casado, José, Pilar Vizcarra, Adrián Martín-Hondarza, Magdalena Blasco, Marta Grandal-Platero, Johannes Haemmerle, Marina Fernández-Escribano, and Alejandro Vallejo. "Impact of Previous Common Human Coronavirus Exposure on SARS-CoV-2-Specific T-Cell and Memory B-Cell Response after mRNA-Based Vaccination." Viruses 15, no. 3 (February 24, 2023): 627. http://dx.doi.org/10.3390/v15030627.
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Objective: T-cell responses against SARS-CoV-2 are observed in unexposed individuals, attributed to previous common human coronavirus (HCoV) infections. We evaluated the evolution of this T-cell cross-reactive response and the specific memory B-cells (MBCs) after the SARS-CoV-2 mRNA-based vaccination and its impact on incident SARS-CoV-2 infections. Methods: This was a longitudinal study of 149 healthcare workers (HCWs) that included 85 unexposed individuals that were subdivided according to previous T-cell cross-reactivity, who were compared to 64 convalescent HCWs. Changes in specific T-cell response and memory B-cell (MBC) levels were compared at baseline and after two doses of the SARS-CoV-2 mRNA-based vaccine. Results: A cross-reactive T-cell response was found in 59% of unexposed individuals before vaccination. Antibodies against HKU1 positively correlated with OC43 and 229E antibodies. Spike-specific MBCs was scarce in unexposed HCWs regardless of the presence of baseline T-cell cross-reactivity. After vaccination, 92% and 96% of unexposed HCWs with cross-reactive T-cells had CD4+ and CD8+ T-cell responses to the spike protein, respectively. Similar results to that were found in convalescents (83% and 92%, respectively). Contrarily, higher than that which was observed in unexposed individuals without T-cell cross-reactivity showed lower CD4+ and CD8+ T-cell responses (73% in both cases, p = 0.03). Nevertheless, previous cross-reactive T-cell response was not associated with higher levels of MBCs after vaccination in unexposed HCWs. During a follow-up of 434 days (IQR, 339–495) after vaccination, 49 HCWs (33%) became infected, with a significant positive correlation between spike-specific MBC levels and isotypes IgG+ and IgA+ after vaccination and a longer time to get infected. Interestingly, T-cell cross-reactivity did not reduce the time to vaccine breakthrough infections. Conclusion: While pre-existing T-cell cross-reactivity enhances the T-cell response after vaccination, it does not increase SARS-CoV-2-specific MBC levels in the absence of previous infection. Overall, the level of specific MBCs determines the time to breakthrough infections, regardless of the presence of T-cell cross-reactivity.
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Schoefbaenker, Michael, Rieke Neddermeyer, Theresa Guenther, Marlin M. Mueller, Marie-Luise Romberg, Nica Classen, Marc T. Hennies, et al. "Surrogate Virus Neutralisation Test Based on Nanoluciferase-Tagged Antigens to Quantify Inhibitory Antibodies against SARS-CoV-2 and Characterise Omicron-Specific Reactivity in a Vaccination Cohort." Vaccines 11, no. 12 (December 8, 2023): 1832. http://dx.doi.org/10.3390/vaccines11121832.
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Virus-specific antibodies are crucial for protective immunity against SARS-CoV-2. Assessing functional antibodies through conventional or pseudotyped virus neutralisation tests (pVNT) requires high biosafety levels. Alternatively, the virus-free surrogate virus neutralisation test (sVNT) quantifies antibodies interfering with spike binding to angiotensin-converting enzyme 2. We evaluated secreted nanoluciferase-tagged spike protein fragments as diagnostic antigens in the sVNT in a vaccination cohort. Initially, spike fragments were tested in a capture enzyme immunoassay (EIA), identifying the receptor binding domain (RBD) as the optimal diagnostic antigen. The sensitivity of the in-house sVNT applying the nanoluciferase-labelled RBD equalled or surpassed that of a commercial sVNT (cPass, GenScript Diagnostics) and an in-house pVNT four weeks after the first vaccination (98% vs. 94% and 72%, respectively), reaching 100% in all assays four weeks after the second and third vaccinations. When testing serum reactivity with Omicron BA.1 spike, the sVNT and pVNT displayed superior discrimination between wild-type- and variant-specific serum reactivity compared to a capture EIA. This was most pronounced after the first and second vaccinations, with the third vaccination resulting in robust, cross-reactive BA.1 construct detection. In conclusion, utilising nanoluciferase-labelled antigens permits the quantification of SARS-CoV-2-specific inhibitory antibodies. Designed as flexible modular systems, the assays can be readily adjusted for monitoring vaccine efficacy.
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Hauge, Solveig, Abdullah Madhun, Rebecca Jane Cox, and Lars Reinhardt Haaheim. "Quality and Kinetics of the Antibody Response in Mice after Three Different Low-Dose Influenza Virus Vaccination Strategies." Clinical and Vaccine Immunology 14, no. 8 (June 27, 2007): 978–83. http://dx.doi.org/10.1128/cvi.00033-07.
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ABSTRACT The threat of a new influenza pandemic has led to renewed interest in dose-sparing vaccination strategies such as intradermal immunization and the use of adjuvanted vaccines. In this study we compared the quality and kinetics of the serum antibody response elicited in mice after one or two immunizations with a split influenza A (H3N2) virus, using three different low-dose vaccination strategies. The mice were divided into four groups, receiving either a low-dose vaccine (3 μg hemagglutinin [HA]) intradermally or intramuscularly with or without aluminum adjuvant or the normal human vaccine dose (15 μg HA) intramuscularly. Sera were collected weekly after vaccination and tested in the hemagglutination inhibition, virus neutralization, and enzyme-linked immunosorbent assays. The antibody responses induced after intradermal or intramuscular low-dose vaccinations were similar and lower than those observed after the human vaccine dose. However, low-dose adjuvanted vaccine elicited a serum antibody response comparable to that elicited by the human dose, although the second immunization did not result in any increase in cross-reactive hemagglutination inhibition antibodies, and the peak serum antibody response was observed 1 week later than in the other vaccination groups. Our murine data suggest that the low-dose intradermal route does not show any obvious advantage over the low-dose intramuscular route in inducing a serum antibody response and that none of the low-dose vaccination strategies is as effective as intramuscular vaccination with the normal human dose. However, the low-dose aluminum-adjuvanted vaccine could present a feasible alternative in case of limited vaccine supply.
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Dangi, Tanushree, Nicole M. Palacio, Sarah Sanchez, and Pablo Penaloza-MacMaster. "Characterization of cross-reactive immunity following coronavirus vaccination or natural infection." Journal of Immunology 206, no. 1_Supplement (May 1, 2021): 103.13. http://dx.doi.org/10.4049/jimmunol.206.supp.103.13.
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Abstract SARS-CoV-2 has infected more than 100 million people worldwide. Several vaccine candidates have been deployed under emergency use authorization, but it is unclear whether a coronavirus (CoV) vaccine can protect against other CoV. To investigate this proof-of-concept, we evaluated cross-reactive immunity following vaccination with a modified vaccinia Ankara expressing SARS-CoV-1 spike protein. We first vaccinated C57BL/6 mice intramuscularly and then measured heterologous antibodies (SARS-CoV-2, OC43 and mouse hepatitis virus, MHV) by ELISA. Interestingly, the SARS-CoV-1 vaccine elicited cross-reactive antibodies that recognize these other CoV. Sera from mice immunized with the SARS-CoV-1 vaccine neutralized SARS-CoV-2 pseudovirus in vitro (5-fold greater than control naïve sera; p=0.007), and transfer of these immune sera into naïve mice provided partial protection after heterologous challenges. Similar cross-reactivity was observed following immunization with a SARS-CoV-2 vaccine, and we mapped a conserved CD8 T cell epitope in both SARS-CoV-1 and CoV-2 spike protein, allowing us to develop an MHC tetramer to track this cross-reactive response. Finally, we interrogated whether a CoV infection could elicit cross-reactive immunity. We show that an OC43 infection generated cross-reactive antibodies against SARS-CoV-2, OC43 and MHV, and conferred partial protection against MHV challenge. In summary, our findings demonstrate that cross-reactive immunity can be elicited by vaccination, providing a framework for the rational design of universal CoV vaccines. Moreover, these data suggest that prior infection with endemic CoV may provide partial protection against other CoVs.
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Zhang, J., C. Vandevyver, P. Stinissen, and J. Raus. "In vivo clonotypic regulation of human myelin basic protein-reactive T cells by T cell vaccination." Journal of Immunology 155, no. 12 (December 15, 1995): 5868–77. http://dx.doi.org/10.4049/jimmunol.155.12.5868.
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Abstract Autoreactive T cells specific for myelin basic protein (MBP) are implicated in the pathogenesis of multiple sclerosis. The mechanism by which MBP-reactive T cells are regulated in vivo remains unknown, but is thought to involve the clonotypic regulatory network that can be induced by immunization with attenuated T cells and TCR peptides. We reported previously that immunization of multiple sclerosis patients with irradiated MBP-reactive T cells (T cell vaccination) induced T cell responses to the immunizing clones, resulting in a clonal depletion of circulating MBP-reactive T cells. In this study, we demonstrated that in the majority of the recipients, MBP-reactive T cells remained undetectable in circulation over a period of 1 to 3 yr after vaccination, while they reappeared in some individuals (three of nine), coinciding with clinical exacerbation. The reappearing MBP-reactive T cells were found to originate from clonal origins different from those of T cells persisting before immunization, suggesting a shift of the T cell repertoire to other determinants of MBP. The immunization induces predominantly CD8+ regulatory T cells capable of lysing the immunizing clones in a clonotype-specific manner. The T cell responses induced by immunization were restricted to the immunizing clones and did not affect MBP-reactive clones not used for immunization. Our data further suggest that different hypervariable regions of the TCR may be involved in the observed clonotypic interaction. This study provides useful information for designing future clinical trials using T cell vaccination and other TCR-based therapeutic strategies.
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Ryder, Alex B., Raffael Nachbagauer, Linda Buonocore, Peter Palese, Florian Krammer, and John K. Rose. "Vaccination with Vesicular Stomatitis Virus-Vectored Chimeric Hemagglutinins Protects Mice against Divergent Influenza Virus Challenge Strains." Journal of Virology 90, no. 5 (December 16, 2015): 2544–50. http://dx.doi.org/10.1128/jvi.02598-15.
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ABSTRACTSeasonal influenza virus infections continue to cause significant disease each year, and there is a constant threat of the emergence of reassortant influenza strains causing a new pandemic. Available influenza vaccines are variably effective each season, are of limited scope at protecting against viruses that have undergone significant antigenic drift, and offer low protection against newly emergent pandemic strains. “Universal” influenza vaccine strategies that focus on the development of humoral immunity directed against the stalk domains of the viral hemagglutinin (HA) show promise for protecting against diverse influenza viruses. Here, we describe such a strategy that utilizes vesicular stomatitis virus (VSV) as a vector for chimeric hemagglutinin (cHA) antigens. This vaccination strategy is effective at generating HA stalk-specific, broadly cross-reactive serum antibodies by both intramuscular and intranasal routes of vaccination. We show that prime-boost vaccination strategies provide protection against both lethal homologous and heterosubtypic influenza challenge and that protection is significantly improved with intranasal vaccine administration. Additionally, we show that vaccination with VSV-cHAs generates greater stalk-specific and cross-reactive serum antibodies than does vaccination with VSV-vectored full-length HAs, confirming that cHA-based vaccination strategies are superior at generating stalk-specific humoral immunity. VSV-vectored influenza vaccines that express chimeric hemagglutinin antigens offer a novel means for protecting against widely diverging influenza viruses.IMPORTANCEUniversal influenza vaccination strategies should be capable of protecting against a wide array of influenza viruses, and we have developed such an approach utilizing a single viral vector system. The potent antibody responses that these vaccines generate are shown to protect mice against lethal influenza challenges with highly divergent viruses. Notably, intranasal vaccination offers significantly better protection than intramuscular vaccination in a lethal virus challenge model. The results described in this study offer insights into the mechanisms by which chimeric hemagglutinin (HA)-based vaccines confer immunity, namely, that the invariant stalk of cHA antigens is superior to full-length HA antigens at inducing cross-reactive humoral immune responses and that VSV-cHA vaccine-induced protection varies by site of inoculation, and contribute to the further development of universal influenza virus vaccines.
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Rouhani, Sherin Juliet, Jovian Yu, Daniel Olson, Yuanyuan Zha, Apameh Pezeshk, Alexandra Cabanov, Athalia R. Pyzer, et al. "Antibody and T cell responses to COVID-19 vaccination in patients receiving anticancer therapies." Journal for ImmunoTherapy of Cancer 10, no. 6 (June 2022): e004766. http://dx.doi.org/10.1136/jitc-2022-004766.
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BackgroundPatients with cancer were excluded from phase 3 COVID-19 vaccine trials, and the immunogenicity and side effect profiles of these vaccines in this population is not well understood. Patients with cancer can be immunocompromised from chemotherapy, corticosteroids, or the cancer itself, which may affect cellular and/or humoral responses to vaccination. PD-1 is expressed on T effector cells, T follicular helper cells and B cells, leading us to hypothesize that anti-PD-1 immunotherapies may augment antibody or T cell generation after vaccination.MethodsAntibodies to the SARS-CoV-2 receptor binding domain (RBD) and spike protein were assessed in patients with cancer (n=118) and healthy donors (HD, n=22) after 1, 2 or 3 mRNA vaccine doses. CD4+ and CD8+ T cell reactivity to wild-type (WT) or B.1.617.2 (delta) spike peptides was measured by intracellular cytokine staining.ResultsOncology patients without prior COVID-19 infections receiving immunotherapy (n=36), chemotherapy (n=15), chemoimmunotherapy (n=6), endocrine or targeted therapies (n=6) and those not on active treatment (n=26) had similar RBD and Spike IgG antibody titers to HDs after two vaccinations. Contrary to our hypothesis, PD-1 blockade did not augment antibody titers or T cell responses. Patients receiving B-cell directed therapies (n=14) including anti-CD20 antibodies and multiple myeloma therapies had decreased antibody titers, and 9/14 of these patients were seronegative for RBD antibodies. No differences were observed in WT spike-reactive CD4+ and CD8+ T cell generation between treatment groups. 11/13 evaluable patients seronegative for RBD had a detectable WT spike-reactive CD4+ T cell response. T cells cross-reactive against the B.1.617.2 variant spike peptides were detected in 31/59 participants. Two patients with prior immune checkpoint inhibitor-related adrenal insufficiency had symptomatic hypoadrenalism after vaccination.ConclusionsCOVID-19 vaccinations are safe and immunogenic in patients with solid tumors, who developed similar antibody and T cell responses compared with HDs. Patients on B-cell directed therapies may fail to generate RBD antibodies after vaccination and should be considered for prophylactic antibody treatments. Many seronegative patients do develop a T cell response, which may have an anti-viral effect. Patients with pre-existing adrenal insufficiency may need to take stress dose steroids during vaccination to avoid adrenal crisis.
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Ramakrishnan, Amritha, Keri Altoff, Andrew Pekosz, and Jay Bream. "Immune Response to Seasonal Influenza Vaccination (92.18)." Journal of Immunology 184, no. 1_Supplement (April 1, 2010): 92.18. http://dx.doi.org/10.4049/jimmunol.184.supp.92.18.
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Abstract The emergence of new pandemic strains of influenza highlights the need to better understand the immune response to vaccination in order to develop novel vaccine strategies. The goal of our study was to identify and assess novel markers of immune activation after vaccination. To this end, 100 healthy adults who received either the seasonal Live Attenuated Vaccine (LAIV) or the Inactivated Vaccine (TIV) were enrolled from 2006-2008. First, we measured the serum antibody titers against vaccine strains of the virus. We found that while TIV induced a robust increase in anti-influenza serum antibody titers, LAIV induced only a modest increase. We next measured the levels of 10 cytokines in the serum of vaccine recipients. Vaccination with TIV resulted in a significant reduction in the levels of TNF-α while LAIV had no effect on any of the measured cytokines. Finally, we assessed the ability of seasonal vaccination to induce neutralizing antibody titers against the pandemic 2009 H1N1 strain. Vaccination with TIV was able to induce a significant increase in cross reactive antibodies against different seasonal H1N1 strains but not against the 2009 pandemic H1N1 strain. In all, these data suggest that 1) different influenza A vaccine formulations induce unique cytokine responses in the periphery and 2) seasonal influenza vaccination does not illicit strong cross-reactive serum antibodies with 2009 H1N1.
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Zhang, Jingwu, and Jef Raus. "T cell vaccination in multiple sclerosis." Multiple Sclerosis Journal 1, no. 6 (June 1996): 353–56. http://dx.doi.org/10.1177/135245859600100615.
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T cell responses to myelin bask protein (MBP) are implicated to play an important role in the pathogenesis of multiple sclerosis (MS). These MBP autoreactive T cells are found to undergo in vivo activation and clonal expansion in patients with MS. They accumulate in the brain compartment and may reside in the brain lesions of patients with MS. As MBP-reactive T cells potentially hold a central position in initiation and perpetuation of the brain inflammation, specific immune therapies designed to deplete them may improve the clinical course of the disease. In this paper, the therapeutic potential of T cell vaccination in the treatment of MS is discussed in context of its immunological and clinical effect The results of our phase one clinical vial indicate that T cell vaccination with inactivated MBP autoreactive T cells induces specific regulatory T cell network of the host immune system to deplete circulating MBP-reactive T cells in a clonotype-specific fashion. The immunity induced by T cell vaccination is clonotype-specific and long-lasting. Our longitudinal clinical evaluation further suggests a moderate reduction of rate of clinical exacerbation, disability score and the brain lesions (measured by magnetic resonance imaging) in vaccinated patients, as compared to matched controls. Our study should encourage further investigation on the treatment efficacy of T cell vaccination and further improvement for its clinical application.
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Ondruska, L., V. Parkanyi, J. Vasicek, R. Jurcik, E. Hanusova, D. Vasicek, A. Balazi, and F. Vizzarri. "Decrease in C-reactive protein levels in rabbits after vaccination with a live attenuated myxoma virus vaccine." Veterinární Medicína 61, No. 10 (October 21, 2016): 571–76. http://dx.doi.org/10.17221/159/2015-vetmed.
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Yu, Cailin, Jeremy C. Burns, William H. Robinson, Paul J. Utz, Peggy P. Ho, Lawrence Steinman, and Alan B. Frey. "Identification of Candidate Tolerogenic CD8+T Cell Epitopes for Therapy of Type 1 Diabetes in the NOD Mouse Model." Journal of Diabetes Research 2016 (2016): 1–12. http://dx.doi.org/10.1155/2016/9083103.
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Type 1 diabetes is an autoimmune disease in which insulin-producing pancreatic isletβcells are the target of self-reactive B and T cells. T cells reactive with epitopes derived from insulin and/or IGRP are critical for the initiation and maintenance of disease, but T cells reactive with other islet antigens likely have an essential role in disease progression. We sought to identify candidate CD8+T cell epitopes that are pathogenic in type 1 diabetes. Proteins that elicit autoantibodies in human type 1 diabetes were analyzed by predictive algorithms for candidate epitopes. Using several different tolerizing regimes using synthetic peptides, two new predicted tolerogenic CD8+T cell epitopes were identified in the murine homolog of the major human islet autoantigen zinc transporter ZnT8 (aa 158–166 and 282–290) and one in a non-βcell protein, dopamineβ-hydroxylase (aa 233–241). Tolerizing vaccination of NOD mice with a cDNA plasmid expressing full-length proinsulin prevented diabetes, whereas plasmids encoding ZnT8 and DβH did not. However, tolerizing vaccination of NOD mice with the proinsulin plasmid in combination with plasmids expressing ZnT8 and DβH decreased insulitis and enhanced prevention of disease compared to vaccination with the plasmid encoding proinsulin alone.
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Tinoco, Mariana, Sérgio Leite, Bebiana Faria, Sara Cardoso, Pedro Von Hafe, Geraldo Dias, Filipa Cardoso, Tamara Pereira, Inocência Machado, and António Lourenço. "Perimyocarditis Following COVID-19 Vaccination." Clinical Medicine Insights: Cardiology 15 (January 2021): 117954682110566. http://dx.doi.org/10.1177/11795468211056634.
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A 39-year-old male was admitted in the emergency room with chest pain. He had been given the second dose of Pfizer–BioNTech COVID-19 vaccine 3 days before. The patient denied taking any other medication beyond the usual. He didn’t feel sick in the previous days/weeks. Laboratory studies revealed elevated serum levels of troponin and C-reactive protein. An autoantibody screen and a serologic panel to detect common viruses were negative. A cardiac MRI showed myocardial edema/inflammation and confirmed the diagnosis of perimyocarditis which was considered to be a consequence of COVID-19 vaccination. Physicians should be aware of the possibility of cardiovascular complications after COVID-19 vaccination.
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Kobie, James, Michael Piepenbrink, Christopher Fucile, Alexander F. Rosenberg, and Madhubanti Basu. "Mixed origins: HIV vaccine induced Env-specific antibodies arise from naive and cross-reactive memory B cells." Journal of Immunology 204, no. 1_Supplement (May 1, 2020): 247.16. http://dx.doi.org/10.4049/jimmunol.204.supp.247.16.
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Abstract The most potent and broad HIV envelope (Env)-specific antibodies (Abs) often when reverted to their inferred germline versions representing the naïve B cell receptor, usually fail to bind Env. This may suggest that the primary B cell population that responds to the initial Env exposure is not exclusively comprised of a naïve population, but also a pre-existing cross-reactive antigen-experienced B cell pool that expands following Env exposure. Previously we isolated 66 gp120 reactive mAbs from participants from HVTN105, a phase I trial testing AIDSVAX B/E (gp120 protein) combined with a DNA immunogen. In order to determine the origin of these mAb producing B cells, we used Miseq-based VH lineage tracking approach and identified several of these mAb lineages in peripheral blood prior to vaccination (pre-immune). Further, several of these pre-immune lineages also persist in the bone marrow ~8 months after the final vaccination, including within in the CD138+ long-lived plasma cell compartment. When tested by ELISA, pre-immune mAbs bound to HIV Env, with relatively lower ability than their post-vaccination forms, but showed higher reactivity than their germline form. The majority of the pre-immune lineage members were IgM, however IgG and IgA members were predominant prior to vaccination and the majority of the pre-immune lineage members exhibited somatic hypermutation. These results may indicate that the vaccine-induced Env-specific antibody lineages originated from a mixed ancestor population of naïve and cross-reactive memory cells.
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"Post COVID Vaccination Reactive Arthritis: A Contemporary Assailant." International Journal of Orthopaedics Research 5, no. 2 (April 5, 2022). http://dx.doi.org/10.33140/ijor.05.02.06.
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The severe acute respiratory syndrome coronavirus 2-induced coronavirus disease 2019 (COVID-19) has had a global spread. While most patients with coronavirus disease 2019 (COVID-19) present with mild or moderate symptoms, 15% may develop severe pneumonia, 5% develop acute respiratory distress syndrome (ARDS), septic shock, and multiple organ failure. Some patients may also experience arthralgia or arthritis. Cases of reactive arthritis have been reported during or after COVID-19. Vaccines play an essential role in preventing the spread. However, almost all types ofvaccines have been reported to be associated with adverse events. With the approval of the use of COVID-19 vaccines, the vaccination program was started in our country and is still continuing. Reactive arthritis (ReA) after vaccination has been reported; however, ReA after COVID-19 vaccination has not been reported widely. We reported a 26-year’sold woman who suffered from an acute ReA on her left knee, left ankle and right wrist joint 8 days after COVID-19 vaccination anddiscussed the etiology and preventive strategy. She presented with oligoarthritic for 12 days eight days after COVID vaccination. Finally, she was diagnosed as ReA after COVID vaccination and was administered systemic steroid. The swelling and pain nearly disappeared after 7 days. On 1month follow-up, her condition was normal. ReA after COVID-19 vaccination is rare. The benefits ofvaccination far outweigh its potential risks and vaccination should be administered according to the currentrecommendations. Further attentions should be put to determine which individual is at higher risk fordeveloping autoimmune diseases after COVID-19 vaccination. More versatile and safer vaccines should beexplored.
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Henze, Larissa, Julian Braun, Lil Meyer-Arndt, Karsten Jürchott, Maike Schlotz, Janine Michel, Marica Grossegesse, et al. "Primary ChAdOx1 vaccination does not reactivate pre-existing, cross-reactive immunity." Frontiers in Immunology 14 (January 31, 2023). http://dx.doi.org/10.3389/fimmu.2023.1056525.
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Currently available COVID-19 vaccines include inactivated virus, live attenuated virus, mRNA-based, viral vectored and adjuvanted protein-subunit-based vaccines. All of them contain the spike glycoprotein as the main immunogen and result in reduced disease severity upon SARS-CoV-2 infection. While we and others have shown that mRNA-based vaccination reactivates pre-existing, cross-reactive immunity, the effect of vector vaccines in this regard is unknown. Here, we studied cellular and humoral responses in heterologous adenovirus-vector-based ChAdOx1 nCOV-19 (AZ; Vaxzeria, AstraZeneca) and mRNA-based BNT162b2 (BNT; Comirnaty, BioNTech/Pfizer) vaccination and compared it to a homologous BNT vaccination regimen. AZ primary vaccination did not lead to measurable reactivation of cross-reactive cellular and humoral immunity compared to BNT primary vaccination. Moreover, humoral immunity induced by primary vaccination with AZ displayed differences in linear spike peptide epitope coverage and a lack of anti-S2 IgG antibodies. Contrary to primary AZ vaccination, secondary vaccination with BNT reactivated pre-existing, cross-reactive immunity, comparable to homologous primary and secondary mRNA vaccination. While induced anti-S1 IgG antibody titers were higher after heterologous vaccination, induced CD4+ T cell responses were highest in homologous vaccinated. However, the overall TCR repertoire breadth was comparable between heterologous AZ-BNT-vaccinated and homologous BNT-BNT-vaccinated individuals, matching TCR repertoire breadths after SARS-CoV-2 infection, too. The reasons why AZ and BNT primary vaccination elicits different immune response patterns to essentially the same antigen, and the associated benefits and risks, need further investigation to inform vaccine and vaccination schedule development.
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Acharya, Indira, Lanaya Williams Smith, Chandralekha Banerjee, Lyn M. Camire, and Radhika Vij. "Reactive Arthritis After Mpox Vaccination." Journal of Community Hospital Internal Medicine Perspectives 14, no. 1 (January 10, 2024). http://dx.doi.org/10.55729/2000-9666.1287.
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Faucher, Benjamin, Rania Assab, Jonathan Roux, Daniel Levy-Bruhl, Cécile Tran Kiem, Simon Cauchemez, Laura Zanetti, Vittoria Colizza, Pierre-Yves Boëlle, and Chiara Poletto. "Agent-based modelling of reactive vaccination of workplaces and schools against COVID-19." Nature Communications 13, no. 1 (March 17, 2022). http://dx.doi.org/10.1038/s41467-022-29015-y.
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AbstractWith vaccination against COVID-19 stalled in some countries, increasing vaccine accessibility and distribution could help keep transmission under control. Here, we study the impact of reactive vaccination targeting schools and workplaces where cases are detected, with an agent-based model accounting for COVID-19 natural history, vaccine characteristics, demographics, behavioural changes and social distancing. In most scenarios, reactive vaccination leads to a higher reduction in cases compared with non-reactive strategies using the same number of doses. The reactive strategy could however be less effective than a moderate/high pace mass vaccination program if initial vaccination coverage is high or disease incidence is low, because few people would be vaccinated around each case. In case of flare-ups, reactive vaccination could better mitigate spread if it is implemented quickly, is supported by enhanced test-trace-isolate and triggers an increased vaccine uptake. These results provide key information to plan an adaptive vaccination rollout.