Relevant bibliographies by topics / Hybrid immunity

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  1. Journal articles
  2. Dissertations / Theses
  3. Books
  4. Book chapters
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Academic literature on the topic 'Hybrid immunity'

Author: Grafiati
Published: 1 February 2025

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Journal articles on the topic "Hybrid immunity"

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Crotty, Shane. "Hybrid immunity." Science 372, no. 6549 (June 24, 2021): 1392–93. http://dx.doi.org/10.1126/science.abj2258.

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Tang, Jinyi, Arka Chaudhuri, Panke Qu, Yue Wu, Kristin Wavell, Marthajoy Spano, Justin Taylor, Shan-lu Liu, William Teague, and Jie Sun. "Respiratory mucosal immunity against SARS-CoV-2 after vaccination and infection." Journal of Immunology 212, no. 1_Supplement (May 1, 2024): 1559_5071. http://dx.doi.org/10.4049/jimmunol.212.supp.1559.5071.

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Abstract The current COVID-19 mRNA vaccine is effective in systemic immune memory but lacks in generating mucosal anti-SARS-CoV-2 immunity. While prior SARS-CoV-2 infection establishes respiratory immunity, its strain-specific nature and limited duration pose challenges for sustained protection. Recent research has shown that hybrid immunity, a combination of vaccination and infection, results in a more robust, durable, and broadly reactive immune response in circulation compared to vaccination or infection alone. However, the characteristics and protective mechanisms of hybrid immunity in the respiratory mucosa are not fully understood. Moreover, it remains to be determined whether mucosal booster vaccines could potentially induce responses that are even stronger and more broadly reactive than hybrid immunity. Here, we collect nasal wash, bronchoalveolar lavage, and blood from controls, vaccinee, convalescents, or hybrid individuals. We found that hybrid individuals displayed higher levels of specific Ab, nAb, and B cells than other groups in the respiratory mucosa. In our mouse models, although hybrid immunity showed significant mucosal humoral and cellular immune responses, an adenovirus-based mucosal vaccine booster induced more robust protective respiratory immunity against SARS-CoV-2 variants. Our findings reveal the mechanisms of protection of hybrid immunity and underscore the importance of developing mucosal vaccine boosters that can emulate heightened mucosal immunity.
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Shi, Meiqing, Liping Su, Sigou Hao, Xulin Guo, and Jim Xiang. "Fusion Hybrid of Dendritic Cells and Engineered Tumor Cells Expressing Interleukin-12 Induces Type 1 Immune Responses against Tumor." Tumori Journal 91, no. 6 (November 2005): 531–38. http://dx.doi.org/10.1177/030089160509100614.

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Aims and Background Dendritic cell (DC)-tumor fusion hybrid vaccinees that facilitate antigen presentation represent a novel powerful strategy in cancer immunotherapy. Preclinical studies have demonstrated that IL-12 promotes specific antitumor immunity mediated by T cells in several types of tumors. In the present study, we investigated the antitumor immunity derived from vaccination of fusion hybrids between DCs and engineered J558/IL-12 myeloma cells secreting Th1 cytokine IL-12. Methods The expression vector pcDNA-IL-12 was generated and transfected into J558 myeloma cells and then bone marrow-derived DCs were fused with engineered J558/IL-12 cells. The antitumor immunity derived from vaccination of the fusion hybrid DC/J558/IL-12 was evaluated in vitro and in vivo. Results DC/J558/IL-12 cells secreted recombinant IL-12 (1.6 ng/mL), and inoculation of BALB/c mice with DC/J558/IL-12 hybrid induced a Th1 dominant immune response and resulted in tumor regression. Immunization of mice with engineered DC/J558/IL-12 hybrid elicited stronger J558 tumor-specific cytotoxic T lymphocyte (CTL) responses in vitro as well as more potent protective immunity against J558 tumor challenge in vivo than immunization with the mixture of DCs and J558/IL-12, J558/IL-12 and J558, respectively. Furthermore, the antitumor immunity mediated by DC/J558/1L-12 tumor cell vaccination in vivo appeared to be dependent on CD8+ CTL. Conclusions These results demonstrate that the engineered fusion hybrid vaccines that combine Th1 cytokine gene-modified tumor cells with DCs may be an attractive strategy for cancer immunotherapy.
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Sizyakina, L. P., V. Ya Zakurskaya, and I. I. Andreeva. "Capacities of hybrid immunity: objective realities." Immunologiya 45, no. 3 (2024): 300–311. http://dx.doi.org/10.33029/1816-2134-2024-45-3-300-311.

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Kanokudom, Sitthichai, Jira Chansaenroj, Suvichada Assawakosri, Nungruthai Suntronwong, Ritthideach Yorsaeng, Lakkhana Wongsrisang, Ratchadawan Aeemjinda, et al. "Real-World Study: Hybrid Immunity against SARS-CoV-2 Influences the Antibody Levels and Persistency Lasting More than One Year." Vaccines 11, no. 11 (November 7, 2023): 1693. http://dx.doi.org/10.3390/vaccines11111693.

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This study investigated the impact of hybrid immunity on antibody responses in the participants who received two to seven doses of the COVID-19 vaccine. The study was conducted between April and June 2023. Out of 771 serum samples analyzed, 71.7% exhibited hybrid immunity (positive for total anti-N Ig), while 28.3% showed vaccine-induced immunity (negative for total anti-N Ig). Participants were categorized based on the number of vaccine doses: 2, 3, 4, and ≥5. The findings highlight a trend where a higher number of vaccine doses received was associated with a lower infection rate. There was no significant difference in total RBD Ig levels between those who received 3, 4, or ≥5 doses in both the hybrid immunity and vaccination alone groups across all observed durations as follows: <6 months, 6 to <9 months, 9 to <12 months, and ≥12 months. Hybrid immunity consistently maintained higher total RBD Ig levels and durability compared to vaccination alone, with estimated half-lives (T1/2) of 189.5 days versus 106.8 days for vaccine alone. This investigation underscored the potential benefit of hybrid immunity and raised questions about the optimal strategies for further vaccine dosing.
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Tatarnikova, V. V., V. I. Dubrovina, N. O. Kiseleva, V. A. Vishnyakov, D. D. Bryukhova, A. B. Pyatidesyatnikova, A. N. Bondaryuk, and S. V. Balakhonov. "Effect of Immunity to SARS-CoV-2 Virus on Blood Cellular Composition." Epidemiology and Vaccinal Prevention 23, no. 2 (May 3, 2024): 50–60. http://dx.doi.org/10.31631/2073-3046-2024-23-2-50-60.

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Relevance. The new coronavirus infection (COVID-19) is still a public health problem and a threat to socio-economic well-being. Most studies have focused predominantly on humoral immunity, and there are no data on the cellular composition of blood in dynamics. Aim. To study the dynamics of changes in blood cellular composition depending on the type of immunity formed (natural, hybrid, breakthrough, postvaccinal) to SARS-CoV-2 virus. Materials and Methods. A total of 130 volunteers participated in the study. Immunophenotyping of peripheral blood leukocytes using flow cytometry was performed. The presence of specific IgG antibodies to N-protein SARS-CoV-2, total IgA and cytokines (IL-4, IL-10, IFN-γ, TNF-α) was assessed in serum by ELISA. Results and Discussion. A statistically significant increase in BL was recorded in volunteers with hybrid immunity 1 month (14,0% (12,3–16,4%)) after vaccination compared to healthy volunteers (9,1% (6,4–10,2%), p = 0,0007) and people with primary COVID-19 infection (10,2% (8,3–12,1%), p = 0,0134). In volunteers with natural and hybrid immunity, as well as in revaccinated people, an increase in B1-cells (CD3-CD19+CD5+CD27-) was observed during 3–9 months of observation. It is shown that the increase of B-lymphocytes with «switched» class of synthesized antibodies was detected in people with breakthrough immunity. Increased levels of T-lymphocytes expressing HLA-DR were recorded in all individuals during 6–9 months of follow-up. Volunteers with breakthrough immunity showed a significant increase in the positivity index when assessing the presence of specific IgG class antibodies to the coronavirus N-protein compared with volunteers with natural and hybrid immunity. Conclusions. Vaccination promotes protective immunity sufficient for timely activation of memory T- and B-cells in breakthrough immunity and maintenance of immunologic efficacy in hybrid immunity against COVID-19. The results help to assess the strain of innate and adaptive immunity in novel coronavirus infection and to fill gaps in the understanding of immunopathogenesis in COVID-19.
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Kodera, Sachiko, Akito Takada, Essam A. Rashed, and Akimasa Hirata. "Projection of COVID-19 Positive Cases Considering Hybrid Immunity: Case Study in Tokyo." Vaccines 11, no. 3 (March 13, 2023): 633. http://dx.doi.org/10.3390/vaccines11030633.

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Since the emergence of COVID-19, the forecasting of new daily positive cases and deaths has been one of the essential elements in policy setting and medical resource management worldwide. An essential factor in forecasting is the modeling of susceptible populations and vaccination effectiveness (VE) at the population level. Owing to the widespread viral transmission and wide vaccination campaign coverage, it becomes challenging to model the VE in an efficient and realistic manner, while also including hybrid immunity which is acquired through full vaccination combined with infection. Here, the VE model of hybrid immunity was developed based on an in vitro study and publicly available data. Computational replication of daily positive cases demonstrates a high consistency between the replicated and observed values when considering the effect of hybrid immunity. The estimated positive cases were relatively larger than the observed value without considering hybrid immunity. Replication of the daily positive cases and its comparison would provide useful information of immunity at the population level and thus serve as useful guidance for nationwide policy setting and vaccination strategies.
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Livieratos, Achilleas, Lars Erik Schiro, Charalambos Gogos, and Karolina Akinosoglou. "Durability of Adaptive Immunity in Immunocompetent and Immunocompromised Patients Across Different Respiratory Viruses: RSV, Influenza, and SARS-CoV-2." Vaccines 12, no. 12 (December 22, 2024): 1444. https://doi.org/10.3390/vaccines12121444.

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Background/Objectives. Research on respiratory virus immunity duration post-vaccination reveals variable outcomes. This study performed a literature review to assess the efficacy and longevity of immune protection post-vaccination against SARS-CoV-2, influenza, and respiratory syncytial virus (RSV), with a focus on immunocompromised populations. Specific objectives included examining humoral and cellular immune responses and exploring the impact of booster doses and hybrid immunity on extending protection. Methods. A literature review was conducted focusing on studies published from January 2014 to November 2024. The search targeted adaptive immunity post-vaccination, natural immunity, and hybrid immunity for SARS-CoV-2, influenza, and RSV. Selection criteria emphasized human populations, adaptive immunity outcomes, and immunocompromised individuals. The PICO framework guided the analysis, culminating in a detailed review of 30 studies. Results. SARS-CoV-2 vaccines exhibited robust initial antibody responses, which waned significantly within six months, necessitating frequent boosters. Influenza and RSV vaccines similarly showed declines in immunity, though some influenza vaccines demonstrated moderate durability. Hybrid immunity, arising from combined natural infection and vaccination, provided more resilient and lasting protection than vaccination alone, especially against emerging variants. Immunocompromised individuals consistently exhibited reduced durability in adaptive immune responses across all studied viruses. Challenges include rapid viral mutations, limiting the broad protection of current vaccines. Conclusions. Immune durability varies significantly across virus types and patient populations. Frequent boosters and hybrid immunity are critical to optimizing protection, particularly for vulnerable groups. The findings underscore the need for adaptable vaccination strategies and advancements in vaccine design to counter rapidly mutating respiratory pathogens effectively.
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Diani, Sara, Erika Leonardi, Attilio Cavezzi, Simona Ferrari, Oriana Iacono, Alice Limoli, Zoe Bouslenko, et al. "SARS-CoV-2—The Role of Natural Immunity: A Narrative Review." Journal of Clinical Medicine 11, no. 21 (October 25, 2022): 6272. http://dx.doi.org/10.3390/jcm11216272.

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Background: Both natural immunity and vaccine-induced immunity to COVID-19 may be useful to reduce the mortality/morbidity of this disease, but still a lot of controversy exists. Aims: This narrative review analyzes the literature regarding these two immunitary processes and more specifically: (a) the duration of natural immunity; (b) cellular immunity; (c) cross-reactivity; (d) the duration of post-vaccination immune protection; (e) the probability of reinfection and its clinical manifestations in the recovered patients; (f) the comparisons between vaccinated and unvaccinated as to the possible reinfections; (g) the role of hybrid immunity; (h) the effectiveness of natural and vaccine-induced immunity against Omicron variant; (i) the comparative incidence of adverse effects after vaccination in recovered individuals vs. COVID-19-naïve subjects. Material and Methods: through multiple search engines we investigated COVID-19 literature related to the aims of the review, published since April 2020 through July 2022, including also the previous articles pertinent to the investigated topics. Results: nearly 900 studies were collected, and 246 pertinent articles were included. It was highlighted that the vast majority of the individuals after suffering from COVID-19 develop a natural immunity both of cell-mediated and humoral type, which is effective over time and provides protection against both reinfection and serious illness. Vaccine-induced immunity was shown to decay faster than natural immunity. In general, the severity of the symptoms of reinfection is significantly lower than in the primary infection, with a lower degree of hospitalizations (0.06%) and an extremely low mortality. Conclusions: this extensive narrative review regarding a vast number of articles highlighted the valuable protection induced by the natural immunity after COVID-19, which seems comparable or superior to the one induced by anti-SARS-CoV-2 vaccination. Consequently, vaccination of the unvaccinated COVID-19-recovered subjects may not be indicated. Further research is needed in order to: (a) measure the durability of immunity over time; (b) evaluate both the impacts of Omicron BA.5 on vaccinated and healed subjects and the role of hybrid immunity.
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Duché, Denis, Aurélie Frenkian, Valérie Prima, and Roland Lloubès. "Release of Immunity Protein Requires Functional Endonuclease Colicin Import Machinery." Journal of Bacteriology 188, no. 24 (September 29, 2006): 8593–600. http://dx.doi.org/10.1128/jb.00941-06.

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ABSTRACT Bacteria producing endonuclease colicins are protected against the cytotoxic activity by a small immunity protein that binds with high affinity and specificity to inactivate the endonuclease. This complex is released into the extracellular medium, and the immunity protein is jettisoned upon binding of the complex to susceptible cells. However, it is not known how and at what stage during infection the immunity protein release occurs. Here, we constructed a hybrid immunity protein composed of the enhanced green fluorescent protein (EGFP) fused to the colicin E2 immunity protein (Im2) to enhance its detection. The EGFP-Im2 protein binds the free colicin E2 with a 1:1 stoichiometry and specifically inhibits its DNase activity. The addition of this hybrid complex to susceptible cells reveals that the release of the hybrid immunity protein is a time-dependent process. This process is achieved 20 min after the addition of the complex to the cells. We showed that complex dissociation requires a functional translocon formed by the BtuB protein and one porin (either OmpF or OmpC) and a functional import machinery formed by the Tol proteins. Cell fractionation and protease susceptibility experiments indicate that the immunity protein does not cross the cell envelope during colicin import. These observations suggest that dissociation of the immunity protein occurs at the outer membrane surface and requires full translocation of the colicin E2 N-terminal domain.
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Dissertations / Theses on the topic "Hybrid immunity"

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Cotter, Paul. "Dietary Selenium in Cultured Hybrid Striped Bass." Thesis, Virginia Tech, 2006. http://hdl.handle.net/10919/32079.

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As aquaculture continues to contribute high quality protein to a greater proportion of the worldâ s growing population, fish producers have been pressured to increase overall production. However, associated with elevated production is greater stress due to crowding, reduced water quality, and other factors. These stressors impact the health and welfare of the farmed animal which has become of increasing concern to a more environmentally aware and health conscious consumer. New strategies must therefore be developed and adopted by the aquaculture industry to counteract negative consumer perceptions of industrial fish production while also stabilizing the industry.

Better nutrition may enhance disease resistance of farmed fish, while fillet accumulations of specific health-related nutrients may simultaneously add value to the final product. This thesis summarizes research undertaken in an effort to enhance the nutritional value of fish by increasing fillet levels of selenium (Se). In addition, various biomarkers of fish health (lysozyme, ceruloplasmin and glutathione peroxidase (GSH-Px) activities), were examined to determine whether dietary Se supplementation had a positive impact upon fish immunocompetence. Moreover, the effect of vaccination was also examined using lysozyme and growth as indicators of fish performance. Hybrid striped bass (HSB), the fourth most valuable farmed fish and fifth in tonnage produced in the United States, were employed as a model animal. Se, an essential component of the antioxidant enzyme, glutathione peroxidase with many established health benefits was supplemented to HSB diets at various concentrations but was found to be without effect upon serum immune proteins or GSH-Px activity. This finding likely reflected the use of fishmeal within the dietary formulation, which possessed relatively high Se levels, together with sufficient storage of tissue Se within the experimental animals. Nevertheless, these studies determined that organic sources of Se were more efficiently accumulated in HSB muscle than traditional inorganic sources. A linear response occurred up to the highest dose used (3.2 mg kg-1) over a 6 week study. Fillet Se accumulation (r2=0.95) proved to be a better indicator than the liver (r2=0.87).Se enhanced fish therefor appear to offer a route of entry for fish producers into the lucrative designer food market - especially since many hundreds of millions of people worldwide are believed to be Se-deficient. Studies undertaken with Se-deficient HSB confirmed findings from the aforementioned research and also indicate that Se-enhanced fillets might be produced using a finishing feed containing 1.5 mg Se kg-1 6-8 weeks prior to harvest. Accumulation of Se using this strategy resulted in a 100g portion of HSB fillets containing between 33-109 µg Se, amounting to a dietary intake of between 25-80 µg Se;a level that would satisfy present daily intake recommendations.

Vaccination of HSB with a Streptococcus iniae oil-in-water vaccine was examined for its potential negative impacts upon HSB production performance. Vaccinated fish did not exhibit any significant reductions in growth but microarray studies revealed that together with many hundreds of genes, four immune-related genes were impacted by this procedure. This thesis discusses the results obtained with regard to their practical implications to the industry and welfare of cultured fish.
Master of Science

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Carnell, George William. "Development of hybrid haemagglutinin pseudotyped lentiviruses to assess heterosubtypic immunity to influenza." Thesis, University of Kent, 2017. https://kar.kent.ac.uk/66363/.

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The influenza virus still causes hundreds of thousands of deaths globally, on top of morbidity and associated economic burden. We are currently at the height of efforts surrounding the development and employment of 'universal' vaccines against this virus, with clinical trials commencing on the most promising candidates. Despite this, the influenza virus poses more of a threat to human life than it ever has previously, with multiple subtypes of pandemic potential circulating around the globe. The key to current efforts lies in the priming of the immune system towards generating long lasting defences against conserved epitopes and conferring heterosubtypic immunity against the surface glycoprotein haemagglutinin. While vaccine strategies have expanded rapidly over recent years with the advent of 'headless' constructs as well as those derived from consensus, mosaic or chimeric sequences, the serological techniques to test how effective these vaccines are, have advanced less rapidly. Classical serological assays have been shown to be ineffective at detecting the antibodies which modern 'universal' vaccines strife to elicit, replaced by ELISA based approaches combined with mouse models measuring in vivo protection. In this thesis, an alternative method for the detection of heterosubtypic antibodies is used in depth across multiple platforms. Influenza pseudotypes have been employed using chimeric haemagglutinin constructs in a comprehensive project aimed at dissecting head and stalk directed antibodies present in human serum. Characterised broadly neutralising monoclonal antibodies have been tested on panels of influenza pseudotypes including divergent bat influenza viruses which hitherto have not been encountered in humans. A further aspect of influenza immunity has been covered in the detection of anti neuraminidase antibodies which have an important role to play in influenza heterosubtypic immunity. Finally, influenza pseudotypes bearing the glycoproteins from the less studied influenza B virus have been assayed in a large scale project aimed at correlating pseudotype assays with classical approaches.
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Liu, Changxin. "Involvement of Polyamines in PAMP-triggered Immunity and Systemic Acquired Resistance (SAR). Extragenic Suppressors of Immune Hybrid Incompatibility." Doctoral thesis, Universitat de Barcelona, 2020. http://hdl.handle.net/10803/671759.

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The main topic of this Thesis is to investigate the contribution of polyamines to defense in Arabidopsis thaliana and the requirement of callose deposition for full expression of effector-triggered immunity in autoimmune hybrids. Due to its accumulation during pathogen infection, I mainly focused on the polyamine putrescine. The interaction between polyamines, reactive oxygen species (ROS) production and salicylic acid pathway activation is also studied in the context of PAMP-triggered immunity (PTI) (Chapter 1) and systemic acquired resistance (SAR) (Chapter 2). The data support a role for putrescine as a priming agent contributing to resistance against pathogens, which can lead to practical applications in the development of PPP (plant protection products). In Chapter 3, I report the involvement of glucan synthase-like 2 and 10 (GSL2 and GSL10), two of the twelve callose biosynthesis genes, in the temperature-dependent immune hybrid incompatibility between natural accessions of Arabidopsis thaliana from North Europe (Ler) and Central Asia (Kas-2), which constitutes a model for the study of effector-triggered immunity (ETI). This work supports that PTI and ETI are not two separate branches of defense, but support each other through mutual potentiation. Overall, we provide evidence for the involvement of polyamines in defense signaling and callose biosynthesis in the establishment of ETI.
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Saade, Carla. "Immune response against SARS-CoV-2 : impact of viral variants, vaccination, and protection against reinfection." Electronic Thesis or Diss., Lyon 1, 2024. http://www.theses.fr/2024LYO10271.

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La pandémie COVID-19 a posé des défis majeurs aux systèmes de santé mondiaux, notamment en raison de la capacité du SARS-CoV-2 à acquérir des mutations. Cela a entraîné l'émergence séquentielle de variants préoccupants (VOCs de l’anglais Variants of concern) tels que Alpha, Beta, Delta, et désormais Omicron qui circule sous forme de sous-variants successifs (BA.1, JN.1, KP.3). Ces VOCs soulèvent des questions sur leur capacité à échapper à la réponse immunitaire induite par une infection et/ou une vaccination. Alors que les campagnes de vaccination se poursuivent, il est crucial d'évaluer comment différents schémas d'immunisation conférés par la vaccination homologue ou hétérologue ainsi que par la combinaison d’une infection et de vaccination (immunité hybride), impactent la réponse immunitaire contre les variants émergents. Grâce à une cohorte prospective de soignants, ce projet de thèse visait à étudier la capacité des VOCs à échapper à la réponse immunitaire, l'efficacité des différents schémas d'immunisation, et la durabilité des réponses immunitaires générées. Nos résultats montrent que les variants Alpha et Beta échappent aux anticorps neutralisants induits par l'immunisation contre la souche ancestrale, indépendamment du schéma d'immunisation. Cette capacité d’échappement immunitaire s'étend au-delà des premiers variants, car Delta et Omicron ont aussi présenté une baisse significative de leur capacité à être neutralisés par les anticorps produits lors d’une immunisation préalable. Ces résultats soulignent la nécessité cruciale de prendre en compte l'évasion immunitaire spécifique aux variants pour définir les seuils de protection et adapter les stratégies de vaccination. En plus de l’échappement immunitaire des VOCs, l'affaiblissement de la réponse immunitaire contribue également à une diminution de la protection contre le SARS-CoV-2 au fil du temps. Nos résultats montrent que le type d'immunisation, infection ou vaccination, impact significativement le pic et la demi-vie des anticorps dirigés contre le domaine de liaison au récepteur (RBD de l’anglais Receptor binding domain). Cela nous a mené à étudier la réponse immunitaire induite par différents schémas de vaccination 6 mois après l'immunisation. Nous avons montré que l'immunité hybride conduit à une réponse immunitaire plus robuste en comparaison à l'immunité induite par l'infection ou la vaccination seule. Cette réponse améliorée est observée à travers divers paramètres tels que la capacité de neutralisation et le pool de cellules B mémoires, et se traduit par une protection significativement améliorée contre le variant Delta. Ainsi, les individus avec une immunité hybride ont un risque d'infection par Delta réduit de 4,5 fois par rapport à ceux ayant reçu une vaccination homologue. Ces résultats soulignent l'importance de prendre en compte ces différences dans les recommandations vaccinales. Néanmoins, des infections dites «breakthrough», c'est-à-dire survenant malgré une vaccination antérieure, sont souvent observées pendant l’ère Omicron chez des individus vaccinés ou même présentant une immunité hybride. Notre étude sur la réponse humorale après une infection «breakthourgh» par BA.1 a révélé que, bien que l'immunité hybride empêche l’augmentation des taux d'IgG4 anti-S et maintient une activité ADCC élevée, elle limite la diversification du pool de cellules B mémoires spécifiques du RBD par rapport à l'immunité induite par la vaccination. Ces résultats indiquent que l’infection «breakthrough» induit des réponses immunitaires distinctes selon les schémas d'immunisation antérieurs, soulignant l’intérêt de considérer l’historique d’immunisation pour personnaliser les recommandations vaccinales. En somme, les résultats obtenus lors de ce travail de thèse soulignent la nécessité d’établir des recommandations vaccinales en fonction des immunisations antérieures pour répondre efficacement aux capacités d’échappement immunitaire des VOCs en circulation
The COVID-19 pandemic has presented significant challenges to global healthcare, largely due SARS-CoV-2’s ability to acquire new mutations. This has led to the sequential emergence of variants of concern (VOCs) such as Alpha, Beta, Delta, and now Omicron that exhibited different successive subvariants (notably BA.1, JN.1, and KP.3). These VOCs have raised concerns about their capacity to escape the immune response induced by infection and/or vaccination. As vaccination campaigns continue worldwide, it is crucial to evaluate how different immunization schemes, including homologous and heterologous vaccinations as well as infection combined with vaccination (hybrid immunity), impact the immune response against emerging variants. With a prospective cohort of healthcare workers, this PhD project aimed to investigate i) the capacity of viral variants to escape the immune response, ii) the effectiveness of different immunization schemes, and iii) the durability of the resulting immune responses. Our findings indicated that the Alpha and Beta variants are able to escape neutralizing antibodies induced by immunization against the ancestral strain, regardless of the immunization scheme. This capacity for immune evasion extends beyond these earlier variants, as both the Delta and Omicron variants also demonstrated significant resistance to neutralization by antibodies elicited through prior immunization. Such findings underscore the critical need to consider variant-specific immune escape when establishing protection thresholds and updating vaccination strategies. In addition to viral immune escape the waning of the immune response also contributes to a decreased protection against SARS-CoV-2. Our results show that the type of immunization, i.e. infection or vaccination, significantly influences the peak levels and half-life of antibodies targeting the receptor binding domain (RBD). This led us to investigate the immune response induced by different immunization schemes 6 months post-immunization. In particular, we showed that hybrid immunity leads to a more robust immune response 6 months post-immunization compared to immunity induced by either infection or vaccination alone. This enhanced response is observed across various immunological parameters, such as neutralization capacity and the pool of memory B cells, and translates into significantly improved protection against the Delta variant. Individuals with hybrid immunity experienced a 4.5-fold reduction in the risk of Delta infection compared to those with immunity induced solely by homologous vaccination. These findings highlight the importance of considering these differences when formulating vaccination recommendations. Nevertheless, breakthrough infections, i.e. infections occurring despite previous vaccination, are frequently reported during the Omicron era among individuals fully-vaccinated and those with hybrid immunity. Our investigation into the humoral immune response following BA.1 breakthrough infection revealed that while hybrid immunity prevents an increase in anti-S IgG4 levels and maintains a high antibody-dependent cellular cytotoxicity (ADCC) activity, it limits the diversification of the RBD-specific memory B cell pool compared to vaccination-induced immunity. Hence, our results indicate that BA.1 breakthrough infection elicits distinct immune responses that vary based on prior immunization schemes, which emphasizes the interest to consider immunization history with the aim to personalize vaccination recommendations. Overall, the results obtained throughout this PhD project emphasize the need to incorporate prior immunization history into ongoing adjustments of vaccination strategies and policies to effectively address the evolving immune escape capabilities of VOCs
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Rigby, Rachel Elizabeth. "Ribonuclease H2, RNA:DNA hybrids and innate immunity." Thesis, University of Edinburgh, 2011. http://hdl.handle.net/1842/6509.

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The activation of the innate immune system is the first line of host defence against infection. Nucleic acids can potently stimulate this response and trigger a series of signalling cascades leading to cytokine production and the establishment of an inflammatory state. Mutations in genes encoding nucleases have been identified in patients with autoimmune diseases, including Aicardi-Goutières syndrome (AGS). This rare childhood inflammatory disorder is characterised by the presence of high levels of the antiviral cytokine interferon-α in the cerebrospinal fluid and blood, which is thought to be produced as a consequence of the activation of the innate immunity by unprocessed self-nucleic acids. This thesis therefore aimed to define the role of one of the AGS nucleases, the Ribonuclease H2 (RNase H2) complex, in innate immunity, and to establish if nucleic acid substrates of this enzyme were able to induce type I interferon production in vitro. The AGS nucleases may function as components of the innate immune response to nucleic acids. Consistent with this hypothesis, RNase H2 was constitutively expressed in immune cells, however, its expression was not upregulated in response to type I interferons. RNase H2-deficient cells responded normally to a range of nucleic acid PAMPs, which implied that a role for RNase H2 as a negative regulator of the immune response was unlikely, in contrast to the reported cellular functions of two other AGS proteins, TREX1 and SAMHD1. Therefore, no clear evidence was found for the direct involvement of RNase H2 in the innate immune response to nucleic acids. An alternative model for the pathogenesis of disease hypothesises that decreased RNase H2 activity within the cell results in an accumulation of RNA:DNA hybrids. To investigate the immunostimulatory potential of such substrates, RNA:DNA hybrids with different physiochemical properties were designed and synthesised. Methods to purify the hybrids from other contaminating nucleic acid species were established and their capacity as activators of the innate immune response tested using a range of in vitro cellular systems. A GU-rich 60 bp RNA:DNA hybrid was shown to be an effective activator of a pro-inflammatory cytokine response exclusively in Flt3-L bone marrow cultures. This response was completely dependent on signalling involving MyD88 and/or Trif, however the specific receptor involved remains to be determined. Reduced cellular RNase H2 activity did not affect the ability of Flt3-L cultures to mount a cytokine response against the RNA:DNA hybrid. These in vitro studies suggested that RNA:DNA hybrids may be a novel nucleic acid PAMP. Taken together, the data in this thesis suggest that the cellular function of RNase H2 is in the suppression of substrate formation rather than as a component of the immune response pathways. Future studies to identify endogenous immunostimulatory RNA:DNA hybrids and the signalling pathways activated by them should provide a detailed understanding of the molecular mechanisms involved in the pathogenesis of AGS and related autoimmune diseases.
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Flatt, Justin Wayne. "STRUCTURAL INSIGHTS INTO RECOGNITION OF ADENOVIRUS BY IMMUNOLOGIC AND SERUM FACTORS." Case Western Reserve University School of Graduate Studies / OhioLINK, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=case1387451692.

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Payelle-Brogard, Béatrice. "Utilisation de cellules hybrides pour l'induction d'une immunité antitumorale chez la souris et l'étude de la suppression de cette réponse." Paris 7, 1985. http://www.theses.fr/1985PA077072.

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L'induction d'une immunité antitumorale contre un fibrosarcome chimioinduit chez la souris peut se faire par injection de cellules hybrides semi-allogeniques provenant de la fusion entre une cellule du fibrosarcome et un fibroblaste allogenique. L'immunité antitumorale ainsi induite se developpe rapidement, elle est médiée par des lymphocytes t spécifiques de la tumeur parentale, actifs in vivo et in vitro et dont l'activité peut etre amplifiée par de l'interleukine-2. Des phénomènes suppresseurs, de nature t, empêchent transitoirement l'expression de cette immunité. Ce modele d'immunisation à ete utilise pour mettre en evidence une depression de l'immunite antitumorale (immunodepression induite par de fortes doses de bcg, immunodepression liee au vieillissement) et a permis de demontrer la presence de cellules t suppressives responsables de cette immunodépression.
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Rodriguez, Marisela Raquel. "Genetic analysis of natural killer cell mediated virus immunity in related strains of New Zealand inbred mice and their hybrid offspring /." 2008. http://wwwlib.umi.com/dissertations/fullcit/3327011.

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Li, Pei-Fen, and 李佩芬. "The influence of Darsan yam-containing diets on the growth performance, antioxidant and immunity indexes of juvenile hybrid tilapia, Oreochromis niloticus × O. aureus." Thesis, 2013. http://ndltd.ncl.edu.tw/handle/18243477671124976170.

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Kan, Stanislav. "Development of airway epithelial targeted nanoparticles loaded with TLR7 agonist for asthma therapy." Thesis, 2021. http://hdl.handle.net/1959.13/1422799.

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Research Doctorate - Doctor of Philosophy (PhD)
Acute asthma flares represent the major cause of healthcare resource consumption and prevention of acute asthma exacerbation remains a major currently unmet therapeutic need in asthma control. Respiratory viruses, most often rhinoviruses (RVs), are the most frequent trigger of acute asthma exacerbations. Airway epithelial cells (AECs) are the site RV infection and initiate the host response to infection which is a key determinant of disease outcome. Endosomal toll like receptor 7 (TLR7) is a potential therapeutic target for asthma exacerbations as stimulation of TLR7 improves antiviral response via induction of type I/ type III interferons (IFNs) and interferon-stimulated genes (ISGs). The challenge is to achieve efficient delivery of TLR7 agonists to activate antiviral immunity in infected AECs. Targeted TLR7 activation in AECs is critical as stimulation of TLR7 in resident immune cells may lead to unwanted induction of pro-inflammatory response. We hypothesized that AEC-targeting nanoparticles (AEC-NPs) offer a solution to this challenge by enabling AEC-targeted delivery of TLR7 agonists to boost antiviral immunity and subsequently inhibit viral replication. In this thesis, we developed and optimised the AEC-NP delivery system and confirmed its targeting specificity in human bronchial epithelial cells. The optimised AEC-NPs were able to efficiently deliver TLR7 agonist CL264 and boost antiviral immune response in both submerged monolayer culture and primary bronchial epithelial cells (from heathy donors and patients with asthma) grown in air-liquid interface (ALI) culture. Finally, the pharmacological response and inflammatory profile of CL264-loaded AEC-NPs were evaluated in vivo.
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Books on the topic "Hybrid immunity"

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Hendricks, Richard Julius. The isolation and characterization of a new phi80-lambda hybrid bacteriophage carrying both the phi80 and lambda immunity genes. 1985.

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Kriangsak, Kittichaisaree. Part II Substantive Law, 7 The Third Alternative of Surrender to a Competent International Criminal Tribunal or a Hybrid Tribunal and its Impediments. Oxford University Press, 2018. http://dx.doi.org/10.1093/law/9780198823292.003.0007.

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The chapter elaborates the practical difficulties and principled opposition to the third alternative of surrender to a competent international criminal tribunal or hybrid tribunals, especially among several States in Africa on the grounds of discriminatory justice and/or the allegedly prevailing rule of customary international law of immunity of the head of State and some other senior State officials. In particular, while Article 27 of the 1998 Rome Statute of the International Criminal Court deems the official position of any person to be irrelevant, Article 98 of the same Statute sets conditions for cooperation with respect to waiver of immunity or consent for surrender of the person, which may not be forthcoming in practice. The author explains how the conflicting rules can be reconciled, if at all.
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Book chapters on the topic "Hybrid immunity"

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Wong, Eugene Y. C., Henry S. C. Yeungz, and Henry Y. K. Lau. "Immunity-based hybrid evolutionary algorithm for multi-objective optimization." In Research and Development in Intelligent Systems XXV, 337–42. London: Springer London, 2009. http://dx.doi.org/10.1007/978-1-84882-171-2_24.

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Xia, Sisi, Xiaoping Huo, Chunfu Zheng, and Jun Chen. "Yeast Two-Hybrid Assay for Investigating Antiviral Innate Immunity." In Methods in Molecular Biology, 213–20. New York, NY: Springer US, 2024. http://dx.doi.org/10.1007/978-1-0716-4108-8_21.

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Li, Meiyi, Zixing Cai, Yuexiang Shi, and Pingan Gao. "A Hybrid Immune Evolutionary Computation Based on Immunity and Clonal Selection for Concurrent Mapping and Localization." In Lecture Notes in Computer Science, 1308–11. Berlin, Heidelberg: Springer Berlin Heidelberg, 2005. http://dx.doi.org/10.1007/11539902_167.

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Israel, Ora, Enrique Estrada-Lobato, and Thomas Neil Pascual. "Infection and Inflammation Imaging." In A Practical Guide for Pediatric Nuclear Medicine, 183–98. Berlin, Heidelberg: Springer Berlin Heidelberg, 2023. http://dx.doi.org/10.1007/978-3-662-67631-8_11.

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AbstractMost commonly infectious processes in children involve the peripheral skeleton, lungs, kidneys, brain, and heart. Pediatric infections are usually of viral and bacterial origins. Fungal etiology can be found, mainly in children with immunodeficiency. Neonates also have immature immunity and are prone to infections with a less favorable prognosis. Conventional techniques used to evaluate infectious and inflammatory processes in children provide high-resolution images but are limited since only insignificant findings are seen in early disease stages and the differential diagnosis with coexisting pathologies and/or post-treatment changes is challenging. Nuclear Medicine procedures play an important role in diagnosing and monitoring pediatric infections, and inflammatory and granulomatous diseases. Several SPECT radiotracers used in the past for functional imaging of infection and inflammatory processes, such as 67Gallium citrate and 111In-labelled WBCs are not being used anymore routinely in pediatric patients and only rarely in adults, mainly in centers with limited or no access to 99mTc-labelled leukocytes (WBCs) and PET imaging. The value of Nuclear Medicine tests has increased with the implementation of hybrid SPECT/CT, PET/CT, and PET/MRI imaging.
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Hassan, Sher. "Tolerance, Resistance to Multiplication and Immunity to Tomato Yellow Top Virus and Potato Leafroll Virus in Lycopersicon Peruvianum and of Its Tomato Hybrid Progenies." In Durability of Disease Resistance, 347. Dordrecht: Springer Netherlands, 1993. http://dx.doi.org/10.1007/978-94-011-2004-3_73.

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Dong, Xinzhou. "Immunityin Distance Protection of Oscillations." In AC/DC Hybrid Large-Scale Power Grid System Protection, 109–40. Singapore: Springer Nature Singapore, 2022. http://dx.doi.org/10.1007/978-981-19-6486-2_3.

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Carlson, Kerstin Bree. "A New African Pluralism in International Criminal Law." In Hybrid Justice, 221–38. Oxford University PressOxford, 2025. https://doi.org/10.1093/oso/9780192893758.003.0011.

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Abstract There is an ongoing disagreement in international criminal law (ICL) regarding sovereign immunity. International humanitarian law takes the possibility of challenging impunity as a central element of its mandate, in part because a fundamental norm of rule of law practice is that no one is above the law, and in part because leaders are those who arguably bear the greatest responsibility for the types of collective harms international humanitarian law would criminalize. This norm does not distinguish between sitting and former heads of state. Across Africa, however, there has been significant pushback regarding prosecuting sitting leaders for atrocity crimes. This has led to what is perhaps the central conflict defining ICL discourse today: a plurality of opinions regarding how sovereignty comports with state-sponsored atrocity crimes. The chapter examines the recent trial of deposed Chadian head of state Hissène Habré to consider questions of pluralism under ICL regarding sovereign immunity. Through a detailed analysis of the work and doctrinal content of the Habré trial, the chapter shows that while the Habré trial is celebrated as an example of bringing a former head of state to justice, the experience of the Habré trial does not change the balance as regards an African pluralism on the question of sovereign immunity.
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Liu, Cuilan. "Hybrid Courts, Hybrid Laws." In Buddhism in Court, 99–130. Oxford University PressNew York, 2024. http://dx.doi.org/10.1093/oso/9780197663332.003.0006.

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Abstract This chapter shows how Buddhists in China engaged with ideas of clerical legal privileges in Indian Buddhism. Instead of fighting for absolute clerical immunity from punishment, Buddhists in China worked with state rulers to create a hybrid court beyond the dichotomy of the Buddhist monastic court and the state court, thus creating a tripartite legal infrastructure to seek more jurisdictional autonomy for the Buddhist establishment to govern its ordained members. This hybrid court was guided by a newly created set of hybrid laws that were established by taking into consideration rules from both the Buddhist monastic law and the state law. Chinese Buddhists began this project of forming the hybrid law and hybrid court in the fourth century ce. This chapter shows how the established tripartite legal infrastructure’s influence has continued to operate subtly within contemporary China, even through dynastic changes, including the end of the empire.
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Žukauskaite, Audrone. "Hybrid Organism." In Organism-Oriented Ontology, 134–51. Edinburgh University Press, 2023. http://dx.doi.org/10.3366/edinburgh/9781399510547.003.0008.

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Chapter 7 discusses symbiosis as a specific kind of biological assemblage. Donna J. Haraway points out the obvious but ignored fact that every living being is dependent on other living beings, such as viruses, bacteria, archaea, etc. Haraway suggests the term ‘sympoiesis’ to refer to collectively producing systems that do not have self-defined spatial or temporal boundaries. These systems are evolutionary and have the potential for change. Thus, the theory of sympoiesis questions the notion of the bounded individual and examines living beings as mutually interconnected and interdependent. Similarly, Scott F. Gilbert argues that there is no such thing as biological individuality; both human and non-human animals are holobionts – organisms coexisting with persistent communities of symbionts. Taking this into account, Haraway suggests sympoiesis as a continuous process of ‘becoming-with’ which creates new networks of collaboration and gives an increased potency to its collaborators. The chapter also discusses the notion of immunity and asks how to define the limit at which coexistence is collaborative and productive, and beyond which it becomes damaging and lethal.
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Pillai, Mamatha M., Garima Malik, and Prakriti Tayalia. "Immunological Aspects of Nanocellulose." In Nanocellulose-based Hybrid Systems for Tissue Engineering, 50–77. Royal Society of Chemistry, 2024. https://doi.org/10.1039/9781837673094-00050.

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This chapter delves into the intricacies of the association between nanocellulose and immunology. It outlines the foundational principles of immunology, differentiating between innate and adaptive immunity. The effects of the source and chemical modifications of nanocellulose on the immune response are highlighted, exploring the comprehensive interactions between nanocellulose and both branches of immunity. Furthermore, the chapter underscores the immunomodulatory properties of nanocellulose, presenting its potential in therapeutic applications and its emerging role in immunotherapy, particularly as a drug delivery system. As we navigate breakthroughs and address challenges in immunotherapeutic applications, the chapter concludes by envisioning the future landscape of nanocellulose in immunology, pinpointing emerging trends and research gaps, and charting the course forward.
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Conference papers on the topic "Hybrid immunity"

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Zhao, Fengqiang, Guangqiang Li, Jialu Du, Chen Guo, Hongying Hu, and Ajith Abraham. "A novel genetic algorithm based on immunity and its application." In 2012 12th International Conference on Hybrid Intelligent Systems (HIS). IEEE, 2012. http://dx.doi.org/10.1109/his.2012.6421396.

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Xiao Liu and Aaron M. Cramer. "Hybrid position observer for brushless DC motor drives with improved noise immunity." In 2016 IEEE Power and Energy Society General Meeting (PESGM). IEEE, 2016. http://dx.doi.org/10.1109/pesgm.2016.7741745.

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gaddour, asma, Amani Kacem, Sana Hatmani, Rahma Ben Jazia, Imen Kharrat, Lilia Bouajina, Anis Maatallah, et al. "Factors associated with hybrid immunity in healthcare workers infected with COVID 19." In ERS Congress 2024 abstracts, PA1324. European Respiratory Society, 2024. http://dx.doi.org/10.1183/13993003.congress-2024.pa1324.

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HarimaM, Katsushige, Kaoru Gotoh, Takayuki Kubo, and Takeshi Ishida. "Design of Hybrid Tapered TEM Horn for Radiated Immunity Test in Close Proximity." In 2020 International Symposium on Antennas and Propagation (ISAP). IEEE, 2021. http://dx.doi.org/10.23919/isap47053.2021.9391160.

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Kuo, Hung-chun, Sin-ting Chen, and Tzong-lin Wu. "Improving the Radiated Immunity of the Strip-Lines Using a Novel Hybrid EBG Structure." In 2006 IEEE Electrical Performane of Electronic Packaging. IEEE, 2006. http://dx.doi.org/10.1109/epep.2006.321237.

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Quansheng, Jiang, and Jia Minping. "Novel Hybrid Clustering Algorithm Incorporating Artificial Immunity into Fuzzy Kernel Clustering for Pattern Recognition." In 2007 Chinese Control Conference. IEEE, 2006. http://dx.doi.org/10.1109/chicc.2006.4347453.

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Zhang, Zihan, and Chunhong Chen. "Improving the immunity of SET/MOS hybrid A/D converters using Boltzmann machine networks." In 2017 IEEE 17th International Conference on Nanotechnology (IEEE-NANO). IEEE, 2017. http://dx.doi.org/10.1109/nano.2017.8117259.

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Fan, YuanYuan, KangFeng Zheng, and YiXian Yang. "Epidemic Model of Mobile Phone Virus for Hybrid Spread Mode with Preventive Immunity and Mutation." In 2010 6th International Conference on Wireless Communications, Networking and Mobile Computing (WiCOM). IEEE, 2010. http://dx.doi.org/10.1109/wicom.2010.5601326.

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Nechaev, Y. B., G. A. Kashenko, and O. A. Plaksenko. "Comparative analysis of interference immunity of adaptive information transmission system with hybrid spectrum spreading and nonadaptive systems." In 2014 East-West Design & Test Symposium (EWDTS). IEEE, 2014. http://dx.doi.org/10.1109/ewdts.2014.7027060.

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Jin, Xuwei, Wei Jin, Hao Zhang, Jianfei Jiang, and Weifeng He. "A 0.2V 2.3pJ/Cycle 28dB output SNR hybrid Markov random field probabilistic-based circuit for noise immunity and energy efficiency." In 2017 IEEE International Symposium on Circuits and Systems (ISCAS). IEEE, 2017. http://dx.doi.org/10.1109/iscas.2017.8050894.

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Reports on the topic "Hybrid immunity"

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Avni, Adi, and Gitta L. Coaker. Proteomic investigation of a tomato receptor like protein recognizing fungal pathogens. United States Department of Agriculture, January 2015. http://dx.doi.org/10.32747/2015.7600030.bard.

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Maximizing food production with minimal negative effects on the environment remains a long-term challenge for sustainable food production. Microbial pathogens cause devastating diseases, minimizing crop losses by controlling plant diseases can contribute significantly to this goal. All plants possess an innate immune system that is activated after recognition of microbial-derived molecules. The fungal protein Eix induces defense responses in tomato and tobacco. Plants recognize Eix through a leucine-rich-repeat receptor- like-protein (LRR-RLP) termed LeEix. Despite the knowledge obtained from studies on tomato, relatively little is known about signaling initiated by RLP-type immune receptors. The focus of this grant proposal is to generate a foundational understanding of how the tomato xylanase receptor LeEix2 signals to confer defense responses. LeEix2 recognition results in pattern triggered immunity (PTI). The grant has two main aims: (1) Isolate the LeEix2 protein complex in an active and resting state; (2) Examine the biological function of the identified proteins in relation to LeEix2 signaling upon perception of the xylanase elicitor Eix. We used two separate approaches to isolate receptor interacting proteins. Transgenic tomato plants expressing LeEix2 fused to the GFP tag were used to identify complex components at a resting and activated state. LeEix2 complexes were purified by mass spectrometry and associated proteins identified by mass spectrometry. We identified novel proteins that interact with LeEix receptor by proteomics analysis. We identified two dynamin related proteins (DRPs), a coiled coil – nucleotide binding site leucine rich repeat (SlNRC4a) protein. In the second approach we used the split ubiquitin yeast two hybrid (Y2H) screen system to identified receptor-like protein kinase At5g24010-like (SlRLK-like) (Solyc01g094920.2.1) as an interactor of LeEIX2. We examined the role of SlNRC4a in plant immunity. Co-immunoprecipitation demonstrates that SlNRC4a is able to associate with different PRRs. Physiological assays with specific elicitors revealed that SlNRC4a generally alters PRR-mediated responses. SlNRC4a overexpression enhances defense responses while silencing SlNRC4 reduces plant immunity. We propose that SlNRC4a acts as a non-canonical positive regulator of immunity mediated by diverse PRRs. Thus, SlNRC4a could link both intracellular and extracellular immune perception. SlDRP2A localizes at the plasma membrane. Overexpression of SlDRP2A increases the sub-population of LeEIX2 inVHAa1 endosomes, and enhances LeEIX2- and FLS2-mediated defense. The effect of SlDRP2A on induction of plant immunity highlights the importance of endomembrane components and endocytosis in signal propagation during plant immune . The interaction of LeEIX2 with SlRLK-like was verified using co- immunoprecipitation and a bimolecular fluorescence complementation assay. The defence responses induced by EIX were markedly reduced when SlRLK-like was over-expressed, and mutation of slrlk-likeusing CRISPR/Cas9 increased EIX- induced ethylene production and SlACSgene expression in tomato. Co-expression of SlRLK-like with different RLPs and RLKs led to their degradation, apparently through an endoplasmic reticulum-associated degradation process. We provided new knowledge and expertise relevant to expression of specific be exploited to enhance immunity in crops enabling the development of novel environmentally friendly disease control strategies.
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Dawson, William O., and Moshe Bar-Joseph. Creating an Ally from an Adversary: Genetic Manipulation of Citrus Tristeza. United States Department of Agriculture, January 2004. http://dx.doi.org/10.32747/2004.7586540.bard.

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Citrus is one of the major agricultural crops common to Israel and the United States, important in terms of nutrition, foreign exchange, and employment. The economy of both citrus industries have been chronically plagued by diseases caused by Citrus tristeza virus (CTV). The short term solution until virus-resistant plants can be used is the use of mild strain cross-protection. We are custom designing "ideal" protecting viruses to immunize trees against severe isolates of CTV by purposely inoculating existing endangered trees and new plantings to be propagated as infected (protected) citrus budwood. We crossed the substantial technological hurdles necessary to accomplish this task which included developing an infectious cDNA clone which allows in vitro manipulation of the virus and methods to then infect citrus plants. We created a series of hybrids between decline-inducing and mild CTV strains, tested them in protoplasts, and are amplifying them to inoculate citrus trees for evaluation and mapping of disease determinants. We also extended this developed technology to begin engineering transient expression vectors based on CTV as tools for genetic improvement of tree crops, in this case citrus. Because of the long periods between genetic transformation and the ultimate assay of mature tree characteristics, there is a great need for an effective system that allows the expression or suppression of target genes in fruiting plants. Virus-based vectors will greatly expedite progress in citrus genetic improvement. We characterized several components of the virus that provides necessary information for designing virus-based vectors. We characterized the requirements of the 3 ’-nontranslated replication promoter and two 3 ’-ORF subgenomic (sg) mRNA controller elements. We discovered a novel type of 5’-terminal sgRNAs and characterized the cis-acting control element that also functions as a strong promoter of a 3 ’-sgRNA. We showed that the p23 gene controls negative-stranded RNA synthesis and expression of 3 ’ genes. We identified which genes are required for infection of plants, which are host range determinants, and which are not needed for plant infection. We continued the characterization of native dRNA populations and showed the presence of five different classes including class III dRNAs that consists of infectious and self-replicating molecules and class V dRNAs that contain all of the 3 ’ ORFs, along with class IV dRNAs that retain non-contiguous internal sequences. We have constructed and tested in protoplasts a series of expression vectors that will be described in this proposal.
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