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1

Levandowski, Roland A., Helen L. Regnery, Eldridge Staton, B. Gail Burgess, Michael S. Williams, and Jessie R. Groothuis. "Antibody Responses to Influenza B Viruses in Immunologically Unprimed Children." Pediatrics 88, no. 5 (November 1, 1991): 1031–36. http://dx.doi.org/10.1542/peds.88.5.1031.

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The cocirculation in several parts of the world of influenza viruses B/Yamagata/16/88 and B/Victoria/2/87, which are genetically and antigenically divergent, has prompted the question of whether immunization with one viral antigen is sufficient for protection against both strains. Twenty-three high-risk infants and young children were immunized with a commercial trivalent influenza vaccine containing the antigens of influenza virus B/Yamagata/16/88. When antibodies against influenza viruses B/Yamagata/16/88 and B/Victoria/2/87 were determined, increases developed uniformly to both in the sera of primed children previously exposed to influenza virus B/Victoria/2/87 by immunization or infection. Antibodies against B/Yamagata/16/88 developed in the sera of unprimed children with titers similar to those of the primed children. However, antibodies to B/ Victoria/2/87 were not detected in the sera of the unprimed children. These data suggest that children with out appropriate immunologic priming may not be protected against an infection with a B/Victoria/2/87 strain after vaccination with a B/Yamagata/16/88 strain. Immunization with more than one influenza B virus strain may be desirable in some high-risk pediatric patients if divergent influenza B viruses circulate.
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Desheva, Yu A., T. A. Smolonogina, E. M. Doroshenko, and L. G. Rudenko. "Development of the quadrivalent live attenuated influenza vaccine including two influenza B lineages – Victoria and Yamagata." Problems of Virology 61, no. 1 (February 28, 2016): 16–20. http://dx.doi.org/10.18821/0507-4088-2016-61-1-16-20.

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This work is devoted to the research of the live attenuated influenza vaccine (LAIV) comprising two reassortant B/USSR/60/69-based vaccine influenza viruses Victoria and Yamagata. the intranasal immunization of the CBA mice with both victoria and yamagata strains induced 100% lung protection against the subsequent infection with the wild-type influenza B viruses of any antigen lineage. the quadrivalent LAIV (qLAIV) comprising both reassortant influenza B viruses Victoria and Yamagata were safe and areactogenic in adult volunteers. Following qLAIV administration the immune response was achieved to both Victoria and Yamagata lineages.
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Costa, Jaline Cabral da, Marilda Mendonça Siqueira, David Brown, Jonathan Oliveira Lopes, Braulia Caetano da Costa, Eric Lopes Gama, and Maria de Lourdes Aguiar-Oliveira. "Vaccine Mismatches, Viral Circulation, and Clinical Severity Patterns of Influenza B Victoria and Yamagata Infections in Brazil over the Decade 2010–2020: A Statistical and Phylogeny–Trait Analyses." Viruses 14, no. 7 (July 5, 2022): 1477. http://dx.doi.org/10.3390/v14071477.

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Worldwide, infections by influenza viruses are considered a major public health challenge. In this study, influenza B vaccine mismatches and clinical aspects of Victoria and Yamagata infections in Brazil were assessed. Clinical samples were collected from patients suspected of influenza infection. In addition, sociodemographic, clinical, and epidemiological information were collected by the epidemiological surveillance teams. Influenza B lineages were determined by real-time RT-PCR and/or Sanger sequencing. In addition, putative phylogeny–trait associations were assessed by using the BaTS program after phylogenetic reconstruction by a Bayesian Markov Chain Monte Carlo method (BEAST software package). Over 2010–2020, B/Victoria and B/Yamagata-like lineages co-circulated in almost all seasonal epidemics, with B/Victoria predominance in most years. Vaccine mismatches between circulating viruses and the trivalent vaccine strains occurred in five of the eleven seasons (45.5%). No significant differences were identified in clinical presentation or disease severity caused by both strains, but subjects infected by B/Victoria-like viruses were significantly younger than their B/Yamagata-like counterparts (16.7 vs. 31.4 years, p < 0.001). This study contributes to a better understanding of the circulation patterns and clinical outcomes of B/Victoria- and B/Yamagata-like lineages in Brazil and advocate for the inclusion of a quadrivalent vaccine in the scope of the Brazilian National Immunization Program.
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4

Baxter, C. M., H. J. Clothier, and K. P. Perrett. "Potential immediate hypersensitivity reactions following immunization in preschool aged children in Victoria, Australia." Human Vaccines & Immunotherapeutics 14, no. 8 (May 10, 2018): 2088–92. http://dx.doi.org/10.1080/21645515.2018.1460293.

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5

Silcock, Rowena, Nigel W. Crawford, Gowri Selvaraj, Alissa McMinn, Margie Danchin, Teresa Lazzaro, and Kirsten P. Perrett. "Subcutaneous nodules following immunization in children; in Victoria, Australia from 2007 to 2016." Vaccine 38, no. 15 (March 2020): 3169–77. http://dx.doi.org/10.1016/j.vaccine.2019.12.066.

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6

Cheng, Daryl R., Kirsten P. Perrett, Sharon Choo, Margie Danchin, Jim P. Buttery, and Nigel W. Crawford. "Pediatric anaphylactic adverse events following immunization in Victoria, Australia from 2007 to 2013." Vaccine 33, no. 13 (March 2015): 1602–7. http://dx.doi.org/10.1016/j.vaccine.2015.02.008.

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7

Campbell, Angela P., Constance Ogokeh, Geoffrey A. Weinberg, Julie A. Boom, Janet A. Englund, John V. Williams, Natasha B. Halasa, et al. "Effect of Vaccination on Preventing Influenza-Associated Hospitalizations Among Children During a Severe Season Associated With B/Victoria Viruses, 2019–2020." Clinical Infectious Diseases 73, no. 4 (January 27, 2021): e947-e954. http://dx.doi.org/10.1093/cid/ciab060.

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Abstract Background The 2019–2020 influenza season was characterized by early onset with B/Victoria followed by A(H1N1)pdm09 viruses. Emergence of new B/Victoria viruses raised concerns about possible vaccine mismatch. We estimated vaccine effectiveness (VE) against influenza-associated hospitalizations and emergency department (ED) visits among children in the United States. Methods We assessed VE among children aged 6 months–17 years with acute respiratory illness and ≤10 days of symptoms enrolled at 7 pediatric medical centers in the New Vaccine Surveillance Network. Combined midturbinate/throat swabs were tested for influenza virus using molecular assays. Vaccination history was collected from parental report, state immunization information systems, and/or provider records. We estimated VE from a test-negative design using logistic regression to compare odds of vaccination among children testing positive vs negative for influenza. Results Among 2029 inpatients, 335 (17%) were influenza positive: 37% with influenza B/Victoria alone and 44% with influenza A(H1N1)pdm09 alone. VE was 62% (95% confidence interval [CI], 52%–71%) for influenza-related hospitalizations, 54% (95% CI, 33%–69%) for B/Victoria viruses, and 64% (95% CI, 49%–75%) for A(H1N1)pdm09. Among 2102 ED patients, 671 (32%) were influenza positive: 47% with influenza B/Victoria alone and 42% with influenza A(H1N1)pdm09 alone. VE was 56% (95% CI, 46%–65%) for an influenza-related ED visit, 55% (95% CI, 40%–66%) for B/Victoria viruses, and 53% (95% CI, 37%–65%) for A(H1N1)pdm09. Conclusions Influenza vaccination provided significant protection against laboratory-confirmed influenza-associated hospitalizations and ED visits associated with the 2 predominantly circulating influenza viruses among children, including against the emerging B/Victoria virus subclade.
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Groothuis, Jessie R., Gordon Meiklejohn, Brian A. Lauer, Myron J. Levin, and Gerard P. Rabalais. "Immunization of High-Risk Infants Younger Than 18 Months of Age with Split-Product Influenza Vaccine." Pediatrics 87, no. 6 (June 1, 1991): 823–28. http://dx.doi.org/10.1542/peds.87.6.823.

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Influenza is an important cause of serious illness in very young children with cardiopulmonary disease. A 4-year study was conducted at two centers to assess immunogenicity and safety of influenza split-product vaccine in children aged 3 to 18 months with bronchopulmonary dysplasia and congenital heart disease. A total of 113 children were studied: 62 children 3 to 5 months of age and 51 children 6 to 18 months of age. Sera were drawn prior to first and second immunization and 3 weeks after second immunization and were tested by hemagglutination inhibition; protection was defined as &gt;1:32. Ninety-five children were surveyed for adverse reactions. Seroresponses were age and antigen specific. Best responses for all ages were to A/Mississippi (H3N2) (97%). Children older than 6 months of age had better seroresponses to A/Leningrad (H3N2) (73%, P &lt; .03) and B/Victoria (62%, P &lt; .02) than did children younger than 6 months of age. Seroconversion rates to the remaining anere low. Only 9% of children experienced adverse reactions; all but one were mild. The immunologic mechanisms responsible for preventing serious influenzal disease and more effective immunization strategies need to be defined for very young high-risk children.
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Ganczak, Maria, Paulina Dubiel, Marzena Drozd-Dąbrowska, Ewelina Hallmann-Szelińska, Karol Szymański, and Lidia B. Brydak. "Quadrivalent Influenza Vaccine-Induced Antibody Response and Influencing Determinants in Patients ≥ 55 Years of Age in the 2018/2019 Season." International Journal of Environmental Research and Public Health 16, no. 22 (November 14, 2019): 4489. http://dx.doi.org/10.3390/ijerph16224489.

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The effects of immunization with subunit inactivated quadrivalent influenza vaccine (QIV) are not generally well assessed in the elderly Polish population. Therefore, this study evaluated vaccine-induced antibody response and its determinants. Methods: Consecutive patients ≥ 55 years old, attending a Primary Care Clinic in Gryfino, Poland, received QIV (A/Michigan/ 45/2015(H1N1)pdm09, A/Singapore/INFIMH-16-0019/2016 (H3N2), B/Colorado/06/2017, B/Phuket/ 3073/2013) between October-December 2018. Hemagglutination inhibition assays measured antibody response to vaccine strains from pre/postvaccination serum samples. Geometric mean titer ratio (GMTR), protection rate (PR) and seroconversion rate (SR) were also calculated. Results: For 108 patients (54.6% males, mean age: 66.7 years) the highest GMTR (61.5-fold) was observed for A/H3N2/, then B/Colorado/06/2017 (10.3-fold), A/H1N1/pdm09 (8.4-fold) and B/Phuket/ 3073/2013 (3.0-fold). Most patients had post-vaccination protection for A/H3N2/ and B/Phuket/3073/ 2013 (64.8% and 70.4%, respectively); lower PRs were observed for A/H1N1/pdm09 (41.8%) and B/Colorado/06/ 2017 (57.4%). The SRs for A/H3N2/, A/H1N1/pdm09, B Victoria and B Yamagata were 64.8%, 38.0%, 46.8%, and 48.2%, respectively. Patients who received QIV vaccination in the previous season presented lower (p < 0.001 and p = 0.03, respectively) response to B Victoria and B Yamagata. Conclusions: QIV was immunogenic against the additional B lineage strain (B Victoria) without significantly compromising the immunogenicity of the other three vaccine strains, therefore, adding a second B lineage strain in QIV could broaden protection against influenza B infection in this age group. As the QIV immunogenicity differed regarding the four antigens, formulation adjustments to increase the antigen concentration of the serotypes that have lower immunogenicity could increase effectiveness. Prior season vaccination was associated with lower antibody response to a new vaccine, although not consistent through the vaccine strains.
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10

Svyatchenko, S. V., A. G. Durymanov, I. M. Susloparov, N. P. Kolosova, N. I. Goncharova, O. V. Petrova, A. V. Epanchintseva, et al. "SEVERE CASES OF SEASONAL INFLUENZA IN RUSSIA IN 2015 - 2016 AND 2016 - 2017." Journal of microbiology epidemiology immunobiology, no. 1 (February 28, 2018): 32–39. http://dx.doi.org/10.36233/0372-9311-2018-1-32-39.

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Aim. Evaluation of seroprevalence of antibodies to influenza A and В viruses and analysis of specimens from severe or fatal influenza cases in Russia in 2015 - 2016 and 2016 - 2017 flu seasons. Materials and methods. Determination of antibody titer in human serum samples in hemagglutination inhibition assay with reference antigens. Isolation of influenza viruses from nasopharyngeal swabs and autopsy material in cell culture. Characterization ofisolated strains. Results. In 2016, compared to 2015, the proportion of serum samples, containing antibodies to influenza viruses A(H 1N1 pdm09) and A(H3N2), increased. During the 2015-2016 season, elevated number of severe and fatal cases of influenza were registered. The majority of circulated strains belonged to the new clade 6B.1 of A(HlNippdm09 viruses. 1% of analyzed isolates carried H275Y amino acid substitution in neuraminidase and were resistant to oseltamivir. In the 2016 - 2017 season, there were less severe cases of influenza. The most prevalent were influenza viruses A(H3N2) and B/Victoria. Isolated H3N2 viruses belonged to the 3C.2a subclade and B/Victoria isolates were from the 1A genetic group. All tested strains were susceptible to neuraminidase inhibitors. Conclusions. Flu seasons 2015 - 2016 and 2016 - 2017 differed in intensity of influenza activity and in the dominant influenza A virus subtype. Immunization with vaccine, comprising new HlNlpdm09-component, is crucial for prophylaxis of influenza infection with viruses from 6B. 1 subclade in the next season. Neuraminidase inhibitors are recommended for influenza treatment.
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11

Pemberton, R. M., R. Jennings, and T. L. Smith. "Morphology and antigenicity studies on reassortant influenza (H3N2) viruses for use in inactivated vaccines." Journal of Hygiene 94, no. 2 (April 1985): 229–39. http://dx.doi.org/10.1017/s002217240006143x.

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SUMMARYThree influenza A (H3N2) reassortant whole virus vaccine strains with differing antibody-inducing capacities in hamsters were investigated morphologically and antigenically. Although initial measurements of virion circumference, from electron micrographs of vaccine preparations, suggested a relationship of small virion size with low immunogenicity, subsequent immunization with, and morphological investigation of, vaccine virions separated on sucrose gradients, failed to obtain populations whose antibody-inducing capacity clearly correlated with constituent virion density, size, morphology or integrity.However, antigenic investigation using single radial haemolysis (SRH) and monoclonal antibodies revealed significant differences in antigenic specificity between the strains. Furthermore, a series of H3N2 isolates, derived using standard reassortment procedures, also showed differences in antigenic specificity in their haemagglutination-inhibition (HI) reactions with monoclonal antibodies after five passages in allantois-on-shell cultures. Variation between these isolates and their A/Victoria parent virus could be detected using SRH and hamster sera raised against each isolate.These results demonstrate variation between candidate influenza A virus vaccine strains, all possessing the same surface (H3N2) glycoproteins, expressed as a consequence of the reassortant system used for their production.
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Adamson, E., N. Yussf, and E. Schreiber. "Using Liver Cancer Prevention Messages to Scale up the Diagnosis and Treatment of People Living With Hepatitis B." Journal of Global Oncology 4, Supplement 2 (October 1, 2018): 132s. http://dx.doi.org/10.1200/jgo.18.32800.

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Background and context: Chronic hepatitis B (CHB) is a major public health issue in Australia, affecting an estimated 238,000 people. If not appropriately managed, chronic hepatitis B infection can cause cirrhosis and liver cancer. Liver cancer has the fastest increasing incidence rate of all cancers in Australia, and its survival is among the lowest. To reduce the burden of liver cancer, more people with CHB need to be diagnosed and treated. The majority of people living in Australia with CHB (61%) were born overseas, and research indicates people have low levels of understanding about hepatitis B, and its link to liver cancer. Cancer Council Victoria developed several communication campaigns to increase testing and diagnosis for hepatitis B in the Vietnamese and south Sudanese communities living in Victoria. Aim: •To raise awareness about hepatitis B and the link to liver cancer in the Vietnamese and south Sudanese community •To increase understanding about diagnosis, vaccination and management •To mobilize the community to talk to their trusted GP about hepatitis and to be tested. Strategy/Tactics: The campaign strategy was designed to address the knowledge barriers to testing for these two communities. To inform the strategy, qualitative focus groups and community interviews were used to identify perceptions of hepatitis B and liver cancer, as well as the barriers and motivators to testing. Both communities identified their local doctor as a trusted source of health information. Two media campaigns were developed featuring a known doctor from each community. An additional campaign was tailored specifically for young south Sudanese people using hip hop music as method of disseminating key messages about liver cancer prevention. Program/Policy process: The campaigns were designed by the Screening, Early Detection and Immunization Team at Cancer in Council Victoria, Australia. Outcomes: Digital metrics and face to face interviews with community members, nurses and doctors were used to assess the impact of the campaigns. Evaluation results also indicated people did visit their doctor to talk about hepatitis B. The success in motivating people to see their doctor was attributed to the campaigns featuring a message about liver cancer being caused by hepatitis B, and it being led by a known and respected doctor from their own community. What was learned: Cancer organizations can target liver cancer prevention efforts to · increase awareness about liver cancer and hepatitis B in at risk communities; · motivate at risk people to visit their doctor for hepatitis B testing, vaccination and treatment by linking the prevention of liver cancer to hepatitis treatment; · tailor communications to the specific needs of different culturally diverse communities; · collaborate closely with communities from culturally diverse backgrounds to ensure campaign messages and calls to action are culturally appropriate.
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Zeng, Dian, Jiabao Xin, Kunyu Yang, Shuxin Guo, Qian Wang, Ying Gao, Huiqing Chen, et al. "A Hemagglutinin Stem Vaccine Designed Rationally by AlphaFold2 Confers Broad Protection against Influenza B Infection." Viruses 14, no. 6 (June 14, 2022): 1305. http://dx.doi.org/10.3390/v14061305.

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Two lineages of influenza B viruses (IBV) co-circulating in human beings have been posing a significant public health burden worldwide. A substantial number of broadly neutralizing antibodies (bnAbs) have been identified targeting conserved epitopes on hemagglutinin (HA) stem domain, posing great interest for universal influenza vaccine development. Various strategies to design immunogens that selectively present these conserved epitopes are being explored. However, it has been a challenge to retain native conformation of the HA stem region, especially for soluble expression in prokaryotic systems. Here, using a structure prediction tool AlphaFold2, we rationally designed a stable stem antigen “B60-Stem-8071”, an HA stem vaccine derived from B/Brisbane/60/2006 grafted with a CR8071 epitope as a linker. The B60-Stem-8071 exhibited better solubility and more stable expression in the E. coli system compared to the naïve HA stem antigen. Immunization with B60-Stem-8071 in mice generated cross-reactive antibodies and protected mice broadly against lethal challenge with Yamagata and Victoria lineages of influenza B virus. Notably, soluble expression of B60-stem-8071 in the E. coli system showed the potential to produce the influenza B vaccine in a low-cost way. This study represents a proof of concept for the rational design of HA stem antigen based on structure prediction and analysis.
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Stepanova, Ekaterina, Elena Krutikova, Pei-Fong Wong, Victoria Matyushenko, Ekaterina Bazhenova, Irina Isakova-Sivak, and Larisa Rudenko. "Safety, Immunogenicity, and Protective Efficacy of a Chimeric A/B Live Attenuated Influenza Vaccine in a Mouse Model." Microorganisms 9, no. 2 (January 27, 2021): 259. http://dx.doi.org/10.3390/microorganisms9020259.

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Influenza A and B viruses cause significant morbidity and mortality worldwide. Current influenza vaccines are composed of three or four strains: A/H1N1, A/H3N2, and B (Victoria and Yamagata lineages). It is of great interest if immunization against both type A and B influenza viruses can be combined in a single vaccine strain, thus reducing the cost of vaccine production and the possibility of strain interference within the multicomponent vaccine. In the current study, we developed an experimental live cold-adapted influenza intertype reassortant (influenza A and B) vaccine on the live attenuated influenza vaccine (LAIV) A/Leningrad/134/17/57 backbone. Hemagglutinin (HA) and neuraminidase (NA) functional domains were inherited from the influenza B/Brisbane/60/2008 strain, whereas their packaging signals were substituted with appropriate fragments of influenza A virus genes. The recombinant A/B virus efficiently replicated in eggs and Madin–Darby Canine Kidney (MDCK) cells under optimal conditions, temperature-sensitive phenotype was maintained, and its antigenic properties matched the influenza B parental virus. The chimeric vaccine was attenuated in mice: after intranasal immunization, viral replication was seen only in nasal turbinates but not in the lungs. Immunological studies demonstrated the induction of IgG antibody responses against the influenza A and B virus, whereas hemagglutination inhibition (HAI) and neutralizing antibodies were detected only against the influenza B virus, resulting in significant protection of immunized animals against influenza B virus challenge. IFNγ-secreting CD8 effector memory T cells (CD44+CD62L−) were detected in mouse splenocytes after stimulation with the specific influenza A peptide (NP366); however, the T-cell response was not sufficient to protect animals against infection with a high-dose mouse-adapted A/California/07/2009 (H1N1pdm09) virus, most probably due to the mismatch of key T-cell epitopes of the H1N1 virus and the LAIV backbone. Overall, generation of the chimeric A/B LAIV virus on a licensed LAIV backbone demonstrated prospects for the development of safe and efficacious vaccine candidates that afford combined protection against both type A and type B influenza viruses; however, further optimization of the T-cell epitope content within the LAIV backbone may be required.
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Elsherif, May, Todd Hatchette, Jason Leblanc, Lingyun Ye, Melissa K. Andrew, Ardith Ambrose, Guy Boivin, et al. "Epidemiology of Influenza Viruses in Canada over the 2011–2012 to 2013–2014 Seasons: A Study from the Serious Outcomes Surveillance (SOS) Network of the Canadian Immunization Research Network (CIRN)." Open Forum Infectious Diseases 4, suppl_1 (2017): S314. http://dx.doi.org/10.1093/ofid/ofx163.735.

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Abstract Background Influenza virus activity varies seasonally and within season. Epidemiology of serious influenza outcomes is contingent on the prevalent circulating strain/s and susceptible age group/s. Given the strain variability over the 2011–2012 through 2013–2014 seasons in Canada, this study examined the clinical and epidemiological profiles of different influenza strains causing adult hospitalizations. Methods During these three influenza seasons, the Serious Outcomes Surveillance (SOS) Network of the Canadian Immunization Research Network (CIRN) enrolled adults hospitalized with acute respiratory illness across Canada. Nasopharyngeal swabs (NPs) from influenza cases were tested for strain characterization using real-time reverse transcriptase polymerase chain reaction (rtRT-PCR). A primary assay differentiated A and B influenza viruses. Subsequently, influenza A viruses were subtyped as H1N1 or H3N2, and influenza B lineages were differentiated as Victoria or Yamagata. Laboratory results were compared with patient demographic data and clinical outcomes. Results Over three consecutive influenza seasons, 3394 cases of hospitalized acute respiratory illness were laboratory-confirmed as influenza. At 72.4%, influenza A was predominant across all seasons, while influenza B caused 27.6%. Most of the influenza A cases were due to H3N2 (58.7%), while H1N1 accounted for 41.3%. For influenza B, the Yamagata lineage was predominant at 88.4% whereas the Victoria lineage accounted for 11.6%. Outcome analyses are presented for each influenza A subtype and influenza B lineage, overall and per season. Considering serious outcomes in patients ≥65, higher proportions of patients hospitalized with the H1N1 strain experienced intensive care unit (ICU) admission and need for mechanical ventilation, while higher proportions of patients hospitalized with B/Yamagata and H3N2 died within 30 days of admission. Conclusion Comprehensive collection of surveillance data paired with NP specimens by the CIRN SOS Network was conducive to broader understanding of influenza strain activity and associated outcomes at the subtype and lineage level. This data is important to make informed recommendations for the use of multicomponent influenza vaccines. Disclosures M. Elsherif, Canadian Institutes of Health Research: Investigator, Research grant. Public Health Agency of Canada: Investigator, Research grant. GSK: Investigator, Research grant. T. Hatchette, GSK: Grant Investigator, Grant recipient; Pfizer: Grant Investigator, Grant recipient. Abbvie: Speaker for a talk on biologics and risk of TB reactivation, Speaker honorarium.M. K. Andrew, GSK: Grant Investigator, Research grant. Pfizer: Grant Investigator, Research grant. Sanofi-Pasteur: Grant Investigator, Research grant. J. McElhaney, GSK Vaccines: Scientific Advisor, Speaker honorarium. A. Mcgeer, Hoffman La Roche: Investigator, Research grant. GSK: Investigator, Research grant. sanofi pasteur: Investigator, Research grant. J. Powis, Merck: Grant Investigator, Research grant. GSK: Grant Investigator, Research grant. Roche: Grant Investigator, Research grant. Synthetic Biologicals: Investigator, Research grant. M. Semret, GSK: Investigator, Research grant. Pfizer: Investigator, Research grant. S. Trottier, Canadian Institutes of Health Research: Investigator, Research grant. L. Valiquette, GSK: Investigator, Research grant. S. McNeil, GSK: Contract Clinical Trials and Grant Investigator, Research grant. Merck: Contract Clinical Trials and Speaker’s Bureau, Speaker honorarium. Novartis: Contract Clinical Trials, No personal renumeration. sanofi pasteur: Contract Clinical Trials, No personal renumeration
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Nott, Rohini, Trevon L. Fuller, Patrícia Brasil, and Karin Nielsen-Saines. "Out-of-Season Influenza during a COVID-19 Void in the State of Rio de Janeiro, Brazil: Temperature Matters." Vaccines 10, no. 5 (May 23, 2022): 821. http://dx.doi.org/10.3390/vaccines10050821.

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An out-of-season H3N2 type A influenza epidemic occurred in the State of Rio de Janeiro, Brazil during October–November 2021, in between the Delta and Omicron SARS-CoV-2 surges, which occurred in July–October 2021 and January–April 2022, respectively. We assessed the contribution of climate change and influenza immunization coverage in this unique, little publicized phenomenon. State weather patterns during the influenza epidemic were significantly different from the five preceding years, matching typical winter temperatures, associated with the out-of-season influenza. We also found a mismatch between influenza vaccine strains used in the winter of 2021 (trivalent vaccine with two type A strains (Victoria/2570/2019 H1N1, Hong Kong/2671/2019 H3N2) and one type B strain (Washington/02/2019, wild type) and the circulating influenza strain responsible for the epidemic (H3N2 Darwin type A influenza strain). In addition, in 2021, there was poor influenza vaccine coverage with only 56% of the population over 6 months old immunized. Amid the COVID-19 pandemic, we should be prepared for out-of-season outbreaks of other respiratory viruses in periods of COVID-19 remission, which underscore novel disease dynamics in the pandemic era. The availability of year-round influenza vaccines could help avoid unnecessary morbidity and mortality given that antibodies rapidly wane. Moreover, this would enable unimmunized individuals to have additional opportunities to vaccinate during out-of-season outbreaks.
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Baker, C. J. "Immunization to Prevent Group B Streptococcal Disease: Victories and Vexations." Journal of Infectious Diseases 161, no. 5 (May 1, 1990): 917–21. http://dx.doi.org/10.1093/infdis/161.5.917.

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Kauerhof, A. Christine, Nour Nicolas, Sudhanshu Bhushan, Eva Wahle, Kate A. Loveland, Daniela Fietz, Martin Bergmann, et al. "Investigation of activin A in inflammatory responses of the testis and its role in the development of testicular fibrosis." Human Reproduction 34, no. 8 (July 24, 2019): 1536–50. http://dx.doi.org/10.1093/humrep/dez109.

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Abstract STUDY QUESTION Does activin A contribute to testicular fibrosis under inflammatory conditions? SUMMARY ANSWER Our results show that activin A and key fibrotic proteins are increased in human testicular biopsies with leukocytic infiltrates and impaired spermatogenesis and in murine experimental autoimmune orchitis (EAO) and that activin A stimulates fibrotic responses in peritubular cells (PTCs) and NIH 3T3 fibroblasts. WHAT IS KNOWN ALREADY Fibrosis is a feature of EAO. Activin A, a regulator of fibrosis, was increased in testes of mice with EAO and its expression correlated with severity of the disease. STUDY DESIGN, SIZE, DURATION This is a cross-sectional and longitudinal study of adult mice immunized with testicular homogenate (TH) in adjuvant to induce EAO, collected at 30 (n = 6), 50 (n = 6) and 80 (n = 5) days after first immunization. Age-matched mice injected with adjuvant alone (n = 14) and untreated mice (n = 15) were included as controls. TH-immunized mice with elevated endogenous follistatin, injected with a non-replicative recombinant adeno-associated viral vector carrying a gene cassette of follistatin (rAAV-FST315; n = 3) or vector with an empty cassette (empty vector controls; n = 2) 30 days prior to the first immunization, as well as appropriate adjuvant (n = 2) and untreated (n = 2) controls, were also examined. Human testicular biopsies showing focal inflammatory lesions associated with impaired spermatogenesis (n = 7) were included. Biopsies showing intact spermatogenesis without inflammation, from obstructive azoospermia patients, served as controls (n = 7). Mouse primary PTC and NIH 3T3 fibroblasts were stimulated with activin A and follistatin 288 (FST288) to investigate the effect of activin A on the expression of fibrotic markers. Production of activin A by mouse primary Sertoli cells (SCs) was also investigated. PARTICIPANTS/MATERIALS, SETTING, METHODS Testicular RNA and protein extracts collected from mice at days 30, 50 and 80 after first immunization were used for analysis of fibrotic marker genes and proteins, respectively. Total collagen was assessed by hydroxyproline assay and fibronectin; collagen I, III and IV, α-smooth muscle actin (α-SMA) expression and phosphorylation of suppressor of mothers against decapentaplegic (SMAD) family member 2 were measured by western blot. Immunofluorescence was used to detect fibronectin. Fibronectin (Fn), αSMA (Acta2), collagen I (Col1a2), III (Col3a1) and IV (Col4a1) mRNA in PTC and NIH 3T3 cells treated with activin A and/or FST288 were measured by quantitative RT-PCR (qRT-PCR). Activin A in SC following tumour necrosis factor (TNF) or FST288 stimulation was measured by ELISA. Human testicular biopsies were analysed by qRT-PCR for PTPRC (CD45) and activin A (INHBA), hydroxyproline assay and immunofluorescence. MAIN RESULTS AND THE ROLE OF CHANCE Production of activin A by SC was stimulated by 25 and 50 ng/ml TNF (P < 0.01, P < 0.001, respectively) as compared to untreated cells. INHBA mRNA was increased in human testicular biopsies with leukocytic infiltrates and impaired spermatogenesis, compared with control biopsies (P < 0.05), accompanied by increased total collagen (P < 0.01) and fibronectin deposition. Total testicular collagen (P < 0.0001) and fibronectin protein expression (P < 0.05) were also increased in EAO, and fibronectin expression was correlated with the severity of the disease (r = 0.9028). In animals pre-treated with rAAV-FST315 prior to immunization with TH, protein expression of fibronectin was comparable to control. Stimulation of PTC and NIH 3T3 cells with activin A increased fibronectin mRNA (P < 0.05) and the production of collagen I (P < 0.001; P < 0.01) and fibronectin (P < 0.05). Moreover, activin A also increased collagen IV mRNA (P < 0.05) in PTC, while αSMA mRNA (P < 0.01) and protein (P < 0.0001) were significantly increased by activin A in NIH 3T3 cells. LARGE SCALE DATA N/A. LIMITATIONS, REASONS FOR CAUTION A limited number of human testicular specimens was available for the study. Part of the study was performed in vitro, including NIH 3T3 cells as a surrogate for testicular fibroblasts. WIDER IMPLICATIONS OF THE FINDINGS Resident fibroblasts and PTC may contribute to the progression of testicular fibrosis following inflammation, and activin A is implicated as a key mediator of this process. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by the National Health and Medical Research Council of Australia, the Victorian Government’s Operational Infrastructure Support Program and the International Research Training Group between Justus Liebig University (Giessen) and Monash University (Melbourne) (GRK 1871/1–2) on `Molecular pathogenesis on male reproductive disorders’ funded by the Deutsche Forschungsgemeinschaft and Monash University. The authors declare no competing financial interests.
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"GENERAL INFORMATION AND STATISTICS." Asia-Pacific Biotech News 05, no. 05 (March 5, 2001): 97–98. http://dx.doi.org/10.1142/s0219030301001525.

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China to Improve Healthcare for Urbanites, Women and Children. North-east China Starts Campaign for AIDS and Sexually Transmitted Disease. Singapore Launches Hep B Immunization Program. Indian Sugar Exports Increase. Mosquito Viral Scare in Victoria, Australia. Myanmar, Japan Sign MOU on Purchase of Buckwheat Seeds.
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Dubiel, P., M. Ganczak, M. Drozd-Dąbrowska, E. Hallmann-Szelińska, K. Szymański, and L. B. Brydak. "Serologic antibody response to quadrivalent influenza vaccination in Polish elderly patients." European Journal of Public Health 29, Supplement_4 (November 1, 2019). http://dx.doi.org/10.1093/eurpub/ckz187.158.

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Abstract Background The effectiveness of immunization with subunit inactivated quadrivalent influenza vaccine (QIV) in the elderly has not been sufficiently estimated. The study objective was to evaluate QIV-induced antibody response and influencing determinants in Polish elderly patients. Methods Consecutive patients ≥55 years old attending the Primary Care Clinic in Gryfino, Poland, received QIV (A/Michigan/45/2015 [A/H1N1/pdm09], A/Singapore/INFIMH-16-0019/2016 [A/H3N2/], B/Colorado/06/2017 [Victoria lineage], B/Phuket/3073/2013 [Yamagata lineage]) between October-December 2018. Hemagglutination-inhibition assays measured antibody response to vaccine strains before/after vaccination. Geometric mean titer (GMT)/titers ratio (GMTR), protection (PR) and response (RR) rates were calculated. Results Among 108 participants (45.4% females; age 55-85, median 67 years) the highest GMTR after vaccination was observed for A/H3N2/(61.5-fold) followed by Victoria lineage (10.3-fold), A/H1N1/pdm09 (8.4-fold) and Yamagata lineage (3.0-fold). Most participants had a post-QIV protection for A/H3N2/and Yamagata lineage vaccine strains (64.8%, 70.4% respectively); lower PR were observed for Victoria lineage (57.4%) and A/H1N1/pdm09 (41.8%). The RR was high for A/H3N2/(91.7%) and Victoria lineage (68.5%), however, not satisfactory for A/H1N1/pdm09 and Yamagata lineage (59.3%, 52.8% respectively). Patients who received influenza vaccination in the previous year presented lower response to the both B strains compared to those who did not (p &lt; 0.0001 and p = 0.03 respectively). Conclusions Although vaccine-induced antibody response in the elderly Polish population was more effective against A/H3N2/and B Victoria, this introductory study supports the use of QIV. Prior season vaccination was associated with lower antibody response to the current vaccination; this was not consistent to vaccine strains. Further research to better investigate QIV effectiveness determinants in the elderly would be of value. Key messages Subunit inactivated quadrivalent influenza vaccine (QIV) is effective in elderly people and should be used. The response to vaccination is not consistent and depends on the strain of influenza virus.
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Giacomelli Cao, Raquel, Lisa Christian, Zhaohui Xu, Lisa Jaramillo, Bennett Smith, Erik A. Karlsson, Stacey Schultz-Cherry, Asuncion Mejias, and Octavio Ramilo. "Early changes in interferon gene expression and antibody responses following influenza vaccination in pregnant women." Journal of Infectious Diseases, July 1, 2021. http://dx.doi.org/10.1093/infdis/jiab345.

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Abstract Background Influenza immunization during pregnancy provides protection to the mother and the infant. Studies in adults and children with inactivated influenza vaccine (IIV) have identified changes in immune gene expression that correlated with antibody responses. Objective To define baseline blood transcriptional profiles and changes induced by IIV in pregnant women and to identify correlates with antibody responses. Methods Pregnant women were immunized with IIV during the 2013-14 and 2014-15 seasons. Blood samples were collected on day (d) 0 (pre-vaccination), d1 and d7 post-vaccination for transcriptional profile analyses; and d0, d30, delivery and cord blood to measure antibody titers. Results Transcriptional analysis demonstrated overexpression of interferon-stimulated genes (ISGs) on d1 and of plasma cell genes on d7. Pre-vaccination ISGs expression and ISGs over-expressed on d1 significantly correlated with increased H3N2, B Yamagata and B Victoria antibody titers. Plasma-cell gene expression on d7 correlated with increased B Yamagata and B Victoria antibody titers. Compared with women vaccinated during the previous influenza season, women who were not vaccinated the prior year showed more frequent significant correlations between ISGs and antibody titers Conclusions Influenza vaccination in pregnant women resulted in enhanced expression of ISGs and plasma cell genes that correlated with antibody responses.
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Булгакова, В. А., Л. Р. Селимзянова, Т. Е. Привалова, and Д. А. Юсупова. "Immunisation of young children against influenza — evidence review." Лечащий врач, no. 10(25) (November 3, 2022). http://dx.doi.org/10.51793/os.2022.25.10.009.

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Грипп является высококонтагиозной вирусной инфекцией и представляет собой серьезное бремя, особенно для детей в возрасте до 5 лет из-за повышенного риска тяжелого течения заболевания и госпитализации. Связанная с гриппом детская смертность в доковидный период регистрировалась ежегодно. Самый высокий уровень смертности регулярно регистрировался среди детей младшего возраста и особенно детей в возрасте до 6 месяцев. Доказано, что вакцинопрофилактика гриппа у детей младшего возраста безопасна и эффективна. Вакцинация против гриппа детей раннего возраста не только защищает эту уязвимую возрастную группу, но и является важным способом снижения передачи гриппа другим лицам из группы риска, а также сокращает использование медицинских услуг, включая применение антибиотиков. Иммунизация против гриппа в текущих эпидемиологических условиях особенно актуальна, поскольку в продолжающуюся пандемию COVID-19 невозможно предсказать интенсивность и сроки предстоящего сезонного подъема гриппа. Для профилактики гриппа у детей применяется любая лицензированная противогриппозная вакцина, соответствующая показаниям, однако в современных условиях приоритетом в профилактике гриппа является использование четырехвалентных вакцин, обеспечивающих развитие наиболее устойчивого иммунного ответа против ключевых штаммов вирусов гриппа. В четырехвалентные противогриппозные вакцины включены два штамма гриппа В линий Yamagata и Victoria в дополнение к штаммам гриппа A (H1N1 и H3N2). Исследования показали, что иммунизация четырехвалентной вакциной, в том числе детей раннего возраста, хорошо переносится и эффективно защищает от любых циркулирующих и антигенно совпадающих штаммов вирусов гриппа. Четырехвалентная инактивированная гриппозная вакцина российского производства полного цикла для профилактики сезонного гриппа – первая в Российской Федерации квадривакцина, одобренная к применению для иммунизации от гриппа детей с 6 месяцев и беременных. Вакцина соответствует всем рекомендациям Всемирной организации здравоохранения по составу и количеству гемагглютинина штамма вируса гриппа – содержит по 15 мкг гемагглютинина вируса гриппа каждого штамма (А(N1N1), A(N3N2), B линия Yamagata, B линия Victoria); не содержит иммуномодуляторов, адъювантов и консервантов; соответствует критериям иммуногенности для инактивированных гриппозных вакцин, принятых в Евросоюзе и Российской Федерации. Influenza is a highly contagious viral infection and poses a serious burden, especially for children under 5 years of age due to an increased risk of severe illness and hospitalization. Influenza-related infant mortality during the pre-Covid period was reported annually. The highest mortality rate was regularly recorded among young children and especially children under the age of 6 months. Influenza vaccination in young children has been proven to be safe and effective. Influenza vaccination of young children not only protects this vulnerable age group, but is also an important way to reduce the transmission of influenza to others at risk, as well as reduce the use of healthcare services, including the use of antibiotics. Immunization against influenza in the current epidemiological conditions is especially relevant, since during the ongoing COVID-19 pandemic, it is impossible to predict the intensity and timing of the upcoming influenza seasonal rise. To prevent influenza in children, any licensed influenza vaccine that meets the indications is used, however, in modern conditions, the priority in influenza prevention is the use of quadrivalent vaccines that ensure the development of the most stable immune response against key strains of influenza viruses. Quadrivalent influenza vaccines include two influenza B strains of the Yamagata and Victoria B lines in addition to influenza A strains (H1N1 and H3N2). Studies have shown that immunization with the quadrivalent vaccine, including in young children, is well tolerated and effectively protects against any circulating and antigenically matched strains of influenza viruses. Russian-made quadrivalent inactivated full-cycle influenza vaccine for the prevention of seasonal influenza is the first quadrivaccine in the Russian Federation approved for use in influenza immunization of children from 6 months of age and pregnant women. The vaccine complies with all World Health Organization recommendations on the composition and amount of hemagglutinin of an influenza virus strain – it contains 15 μg of influenza virus hemagglutinin of each strain (А(N1N1), A(N3N2), B line Yamagata, B line Victoria); does not contain immunomodulators, adjuvants and preservatives; meets the immunogenicity criteria for inactivated influenza vaccines adopted in the European Union and the Russian Federation.
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Caldera, Freddy, Luke Hillman, Sumona Saha, Arnold Wald, Ian Grimes, Youqi Zhang, Abigail R. Sharpe, Mark Reichelderfer, and Mary S. Hayney. "Immunogenicity of High Dose Influenza Vaccine for Patients with Inflammatory Bowel Disease on Anti-TNF Monotherapy: A Randomized Clinical Trial." Inflammatory Bowel Diseases, August 24, 2019. http://dx.doi.org/10.1093/ibd/izz164.

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Abstract Background Patients with inflammatory bowel disease (IBD) on anti-tumor necrosis factor alpha (TNF) agents may have lower immune response to the influenza vaccine. We aimed to evaluate the immunogenicity of the high dose (HD) vs standard dose (SD) influenza vaccine in patients with IBD on anti-TNF monotherapy. Methods We performed a randomized clinical trial at a single academic center evaluating the immunogenicity of the HD vs SD influenza vaccine in patients with IBD on anti-TNF monotherapy. Influenza antibody concentration was measured at immunization, at 2 to 4 weeks postimmunization, and at 6 months. Results Sixty-nine patients with IBD were recruited into the study, 40 on anti-TNF monotherapy, and 19 on vedolizumab, along with 20 healthy controls (HC). Patients with IBD receiving the HD influenza vaccine had significantly higher H3N2 postimmunization antibodies compared with those who received the SD influenza vaccine (160 [interquartile range 80 to 320] vs 80 [interquartile range 40 to 160]; P = 0.003). The H1N1 postimmunization levels were not significantly higher in the HD influenza vaccine (320 [interquartile range 150 to 320] vs 160 [interquartile range 80 to 320]; P = 0.18). Patients with IBD receiving the HD influenza vaccine and those on vedolizumab who received SD had equivalent antibody concentrations to HC (H1N1 P = 0.85; H3N2 P = 0.23; B/Victoria P = 0.20 and H1N1 P = 0.46; H3N2 P = 0.21; B/Victoria P = 1.00, respectively). Conclusions Patients with IBD on anti-TNF monotherapy receiving the HD influenza vaccine had significantly higher postimmunization antibody levels compared with SD vaccine. Clinicaltrials.gov (#NCT02461758).
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Piepenbrink, Michael S., Aitor Nogales, Madhubanti Basu, Christopher F. Fucile, Jane L. Liesveld, Michael C. Keefer, Alexander F. Rosenberg, Luis Martinez-Sobrido, and James J. Kobie. "Broad and Protective Influenza B Virus Neuraminidase Antibodies in Humans after Vaccination and their Clonal Persistence as Plasma Cells." mBio 10, no. 2 (March 12, 2019). http://dx.doi.org/10.1128/mbio.00066-19.

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ABSTRACTAlthough most seasonal inactivated influenza vaccines (IIV) contain neuraminidase (NA), the extent and mechanisms of action of protective human NA-specific humoral responses induced by vaccination are poorly resolved. Due to the propensity of influenza virus for antigenic drift and shift and its tendency to elicit predominantly strain-specific antibodies, humanity remains susceptible to waves of new strains of seasonal viruses and is at risk from viruses with pandemic potential for which limited or no immunity may exist. Here we demonstrate that the use of IIV results in increased levels of influenza B virus (IBV) NA-specific serum antibodies. Detailed analysis of the IBV NA B cell response indicates concurrent expansion of IBV NA-specific peripheral blood plasmablasts 7 days after IIV immunization which express monoclonal antibodies with broad and potent antiviral activity against both IBV Victoria and Yamagata lineages and prophylactic and therapeutic activity in mice. These IBV NA-specific B cell clonal lineages persisted in CD138+long-lived bone marrow plasma cells. These results represent the first demonstration that IIV-induced NA human antibodies can protect and treat influenza virus infectionin vivoand suggest that IIV can induce a subset of IBV NA-specific B cells with broad protective potential, a feature that warrants further study for universal influenza vaccine development.IMPORTANCEInfluenza virus infections continue to cause substantial morbidity and mortality despite the availability of seasonal vaccines. The extensive genetic variability in seasonal and potentially pandemic influenza strains necessitates new vaccine strategies that can induce universal protection by focusing the immune response on generating protective antibodies against conserved targets such as regions within the influenza neuraminidase protein. We have demonstrated that seasonal immunization stimulates neuraminidase-specific antibodies in humans that are broad and potent in their protection from influenza B virus when tested in mice. These antibodies further persist in the bone marrow, where they are expressed by long-lived antibody-producing cells, referred to here as plasma cells. The significance in our research is the demonstration that seasonal influenza immunization can induce a subset of neuraminidase-specific B cells with broad protective potential, a process that if further studied and enhanced could aid in the development of a universal influenza vaccine.
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Vigil, Adam, Natalia Frias-Staheli, Teresa Carabeo, and Michael Wittekind. "Airway Delivery of Anti-influenza Monoclonal Antibodies Results in Enhanced Antiviral Activities and Enables Broad-Coverage Combination Therapies." Journal of Virology 94, no. 22 (August 26, 2020). http://dx.doi.org/10.1128/jvi.00052-20.

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ABSTRACT Effective and reliable anti-influenza treatments are acutely needed and passive immunizations using broadly neutralizing anti-influenza monoclonal antibodies (bNAbs) are a promising emerging approach. Because influenza infections are initiated in and localized to the pulmonary tract, and newly formed viral particles egress from the apical side of the lung epithelium, we compared the effectiveness of hemagglutinin (HA) stalk-binding bNAbs administered through the airway (intranasal or via nebulization) versus the systemic route (intraperitoneal or intravenous). Airway deliveries of various bNAbs were 10- to 50-fold more effective than systemic deliveries of the same bNAbs in treating H1N1, H3N2, B/Victoria-, and B/Yamagata-lineage influenza viral infections in mouse models. The potency of airway-delivered anti-HA bNAbs was highly dependent on antiviral neutralization activity, with little dependence on the effector function of the antibody. In contrast, the effectiveness of systemically delivered anti-HA bNAbs was not dependent on antiviral neutralization, but critically dependent on antibody effector functions. Concurrent administration of a neutralizing/effector function-positive bNAb via the airway and systemic routes showed increased effectiveness. The small amount of airway-delivered bNAbs needed for effective influenza treatment creates the opportunity to combine potent bNAbs with different anti-influenza specificities to generate a cost-effective antiviral therapy that provides broad coverage against all circulating influenza strains infecting humans. A 3 mg/kg dose of the novel triple antibody combination CF-404 (i.e., 1 mg/kg of each component bNAb) delivered to the airway was shown to effectively prevent weight loss and death in mice challenged with ten 50% lethal dose (LD50) inoculums of either H1N1, H3N2, B/Victoria-lineage, or B/Yamagata-lineage influenza viruses. IMPORTANCE Influenza causes widespread illness in humans and can result in morbidity and death, especially in the very young and elderly populations. Because influenza vaccination can be poorly effective some years, and the immune systems of the most susceptible populations are often compromised, passive immunization treatments using broadly neutralizing antibodies is a promising therapeutic approach. However, large amounts of a single antibody are required for effectiveness when delivered through systemic administration (typically intravenous infusion), precluding the feasible dosing of antibody combinations via this route. The significance of our research is the demonstration that effective therapeutic treatments of multiple relevant influenza types (H1N1, H3N2, and B) can be achieved by airway administration of a single combination of relatively small amounts of three anti-influenza antibodies. This advance exploits the discovery that airway delivery is a more potent way of administering anti-influenza antibodies compared to systemic delivery, making this a feasible and cost-effective therapeutic approach.
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Myers, Mallory L., John R. Gallagher, De’Marcus D. Woolfork, Regan K. Stradtmann-Carvalho, Samantha Maldonado-Puga, Kevin W. Bock, Seyhan Boyoglu-Barnum, et al. "Impact of adjuvant: Trivalent vaccine with quadrivalent-like protection against heterologous Yamagata-lineage influenza B virus." Frontiers in Immunology 13 (September 30, 2022). http://dx.doi.org/10.3389/fimmu.2022.1002286.

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As new vaccine technologies and platforms, such as nanoparticles and novel adjuvants, are developed to aid in the establishment of a universal influenza vaccine, studying traditional influenza split/subunit vaccines should not be overlooked. Commercially available vaccines are typically studied in terms of influenza A H1 and H3 viruses but influenza B viruses need to be examined as well. Thus, there is a need to both understand the limitations of split/subunit vaccines and develop strategies to overcome those limitations, particularly their ability to elicit cross-reactive antibodies to the co-circulating Victoria (B-V) and Yamagata (B-Y) lineages of human influenza B viruses. In this study, we compared three commercial influenza hemagglutinin (HA) split/subunit vaccines, one quadrivalent (H1, H3, B-V, B-Y HAs) and two trivalent (H1, H3, B-V HAs), to characterize potential differences in their antibody responses and protection against a B-Y challenge. We found that the trivalent adjuvanted vaccine Fluad, formulated without B-Y HA, was able to produce antibodies to B-Y (cross-lineage) on a similar level to those elicited from a quadrivalent vaccine (Flucelvax) containing both B-V and B-Y HAs. Interestingly, Fluad protected mice from a lethal cross-lineage B-Y viral challenge, while another trivalent vaccine, Fluzone HD, failed to elicit antibodies or full protection following challenge. Fluad immunization also diminished viral burden in the lungs compared to Fluzone and saline groups. The success of a trivalent vaccine to provide protection from a cross-lineage influenza B challenge, similar to a quadrivalent vaccine, suggests that further analysis of different split/subunit vaccine formulations could identify mechanisms for vaccines to target antigenically different viruses. Understanding how to increase the breadth of the immune response following immunization will be needed for universal influenza vaccine development.
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Giles, Michelle L., Mary-Ann Davey, and Euan M. Wallace. "Associations Between Maternal Immunisation and Reduced Rates of Preterm Birth and Stillbirth: A Population Based Retrospective Cohort Study." Frontiers in Immunology 12 (September 7, 2021). http://dx.doi.org/10.3389/fimmu.2021.704254.

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Stillbirth and preterm birth (PTB) remain two of the most important, unresolved challenges in modern pregnancy care. Approximately 10% of all births are preterm with nearly one million children dying each year due to PTB. It remains the most common cause of death among children under five years of age. The numbers for stillbirth are no less shocking with 2.6 million babies stillborn each year. With minimal impact on the rate of these adverse birth outcomes over the past decade there is an urgent need to identify more effective interventions to tackle these problems. In this retrospective cohort study, we used whole-of-population data, to determine if maternal immunization during pregnancy against influenza and/or pertussis, is associated with a lower risk of PTB, delivering a small-for-gestational age (SGA) infant, developing preeclampsia or stillbirth. Women with a singleton pregnancy at 28 or more weeks’ gestation delivering in Victoria, Australia from July 2015 to December 2018 were included in the analysis. Log-binomial regression was used to measure the relationship between vaccination during pregnancy against influenza and against pertussis, with preterm birth, SGA, preeclampsia and stillbirth. Variables included in the adjusted model were maternal age, body mass index, first or subsequent birth, maternal Indigenous status, socio-economic quintile, smoking, public or private maternity care and metropolitan or rural location of the hospital. Women who received influenza vaccine were 75% less likely to have a stillbirth (aRR 025; 95% CI 0.20, 0.31), and 31% less likely to birth &lt;37 weeks (aRR 0.69; 95% CI 0.66, 0.72). Women who received pertussis vaccine were 77% less likely to have a stillbirth (aOR 0.23; 95% CI 0.18, 0.28) and 32% less likely to birth &lt;37 weeks gestation (aRR 0.68; 95% CI 0.66, 0.71). Vaccination also reduced the odds of small for gestational age by 13% and reduced the odds of pre-eclampsia when restricted to primiparous women. This association was seen over four different influenza seasons and independent of the time of year suggesting that any protective effect on obstetric outcomes afforded by maternal vaccination may not be due to a pathogen-specific response but rather due to pathogen-agnostic immune-modulatory effects.
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Barton, Shanna M., Aaron W. Calhoun, Carrie A. Bohnert, Sara Multerer, Victoria A. Statler, and Gary S. Marshall. "573. AIMS-trained Residents Exhibit Specific Communication Skills During Virtual Encounters with Standardized Vaccine-Hesitant Parents Following an Online Training Program." Open Forum Infectious Diseases 9, Supplement_2 (December 1, 2022). http://dx.doi.org/10.1093/ofid/ofac492.626.

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Abstract Background There are no accepted best practices for counseling vaccine-hesitant parents, and training in this area is not required in residency. In a prior study (J Pediatr 2022;241:203-11), we demonstrated that in-person training in a structured communication strategy called AIMS (Announce, Inquire, Mirror, Secure) resulted in behaviors of interest during live encounters with standardized patients (SPs) portraying vaccine-hesitant parents. We investigated whether similar effects would be seen if training and SP encounters occurred in a virtual environment. Methods Pediatrics and Medicine-Pediatrics residents were randomized to receive either AIMS or control training. Subjects underwent pre- and post-training SP encounters simulating an immunization visit for a 4-month-old. SP case materials were modified to more closely approximate well-intentioned reluctance to vaccinate and allow for more authentic interaction. Encounters were video-recorded and assessed by 3 raters using the Vaccine Hesitancy Communication Assessment (VHCA), developed and characterized in the initial study but modified based on factor analysis to improve reliability and validity. Subject confidence and SP evaluations of the encounter were assessed pre- and post-training. Investigators, subjects, SPs, and video raters were blinded to treatment allocation. Results Fifty-three subjects completed the protocol and 47 had complete video files. Subject confidence improved in both groups (Panel A). No differences in SP evaluations were detected between groups (B). Preliminary analysis demonstrated that AIMS behaviors were more commonly detected among AIMS-trained subjects than control, as evidenced by an increase in VHCA score (C). Conclusion Communication training and assessment using SPs were both successfully transitioned to a virtual environment; this opens the possibility of efficient training and assessment of residents who are not located on site. Training increased confidence non-specifically. Encounters with SPs can serve as a model to detect learned vaccine-specific communication behaviors among resident providers, but post-encounter assessments by SPs remained insensitive to differences in those behaviors despite modification of the case materials. Disclosures Shanna M. Barton, MD, M.Sc., Sanofi Pasteur: Grant/Research Support Aaron W. Calhoun, MD, FSSH, Sanofi-Pasteur: Grant/Research Support|Society for Simulation in Healthcare: Board Member|Society for Simulation in Healthcare: Honoraria Victoria A. Statler, M.D., M.Sc., Astellas: University Research Support|Gilead: University Research Support|Pfizer: Advisor/Consultant|Sanofi: University Research Support|Seqirus: Advisor/Consultant Gary S. Marshall, MD, GlaxoSmithKline: Advisor/Consultant|GlaxoSmithKline: Grant/Research Support|GlaxoSmithKline: Honoraria|Merck: Advisor/Consultant|Merck: Grant/Research Support|Merck: Honoraria|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Pfizer: Honoraria|Sanofi: Advisor/Consultant|Sanofi: Grant/Research Support|Sanofi: Honoraria|Seqirus: Advisor/Consultant|Seqirus: Grant/Research Support|Seqirus: Honoraria.
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Rubincam, Clara, Devon Greyson, Constance Haselden, Robin Saunders, and Julie A. Bettinger. "Is the pre-natal period a missed opportunity for communicating with parents about immunizations? Evidence from a longitudinal qualitative study in Victoria, British Columbia." BMC Public Health 22, no. 1 (February 5, 2022). http://dx.doi.org/10.1186/s12889-022-12658-3.

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Abstract Background Growing evidence shows that many parents begin the decision-making process about infant vaccination during pregnancy and these decisions – once established – may be resistant to change. Despite this, many interventions targeting vaccination are focused on communicating with parents after their baby is born. This suggests that the prenatal period may constitute a missed opportunity for communicating with expectant parents about infant vaccination. Methods Using a longitudinal qualitative design, we conducted two interviews (prepartum and postpartum) with women (n = 19) to explore the optimal timing of vaccination information. The data were analyzed thematically, and examined across all sets of pre- and post-partum interviews as well as within each individual participant to draw out salient themes. Results Most participants formed their intentions to vaccinate before the baby was born and indicated that they would welcome information about vaccination from their maternity care providers. However, few individuals recalled their maternity care providers initiating vaccination-related conversations with them. Conclusion The prenatal period is an important time to begin conversations with expectant parents about vaccinating their infants, particularly if these conversations are initiated by trusted maternity care providers. More information is needed on how maternity care providers can be better supported to have these conversations with their patients.
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30

Khademi Habibabadi, Sedigheh, Christopher Palmer, Gerardo Luis Dimaguila, Muhammad Javed, Hazel J. Clothier, and Jim Buttery. "AIDH Summit 2022 - Automated social media surveillance for detection of vaccine safety signals: a validation study." Applied Clinical Informatics, November 9, 2022. http://dx.doi.org/10.1055/a-1975-4061.

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Background: Social media platforms have emerged as a valuable data source for public health research and surveillance. Monitoring of social media and user-generated data on the web enables timely and inexpensive collection of information, overcoming time lag and cost of traditional health reporting systems. Objectives: To identify personally experienced COVID-19 vaccine reactions expressed on Twitter and validate the findings against an established vaccine reactions reporting system. Methods: We collected around three million tweets from 1.4 million users between 1 February 2021 – 31 January 2022, using COVID-19 vaccines and vaccine reactions keyword lists. We performed topic modelling on a sample of the data and applied a modified F1 scoring technique to identify a topic that best differentiated vaccine-related personal health mentions. We then manually annotated 4,000 of the records from this topic, which were used to train a transformer-based classifier to identify likely personally experienced vaccine reactions. Applying the trained classifier to the entire dataset allowed us to select records we could use to quantify potential vaccine side effects. Adverse events following immunization (AEFI) referred to in these records were compared with those reported to the state of Victoria’s spontaneous vaccine safety surveillance system, SAEFVIC. Results: The most frequently mentioned potential vaccine reactions generally aligned with SAEFVIC data. Notable exceptions were increased Twitter reporting of bleeding-related AEFI and allergic reactions, and more frequent SAEFVIC reporting of cardiac AEFI. Conclusions: Social media conversation can be used as a supplementary data source for detecting vaccine adverse event mentions. More work is required to verify the data.
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