A cross-immunization model for the extinction of old influenza strains.
Ontology highlight
ABSTRACT:
SUBMITTER: Uekermann F
PROVIDER: S-EPMC4865727 | biostudies-other | 2016
REPOSITORIES: biostudies-other
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Project description:Influenza immunization coverage among Canadian health care personnel remains below national targets. Targeting this group is of particular importance given their elevated risk of influenza infection, role in transmission and influence on patients' immunization status. We examined influenza immunization coverage in health care personnel in Canada, reasons for not being immunized and the impact of "vaccinate-or-mask" influenza prevention policies.In this national cross-sectional study, we pooled data from the 2007 to 2014 cycles of the Canadian Community Health Survey and restricted it to respondents who reported a health care occupation. Using bootstrapped survey weights, we examined immunization coverage by occupation and by presence of vaccinate-or-mask policies, and reasons for not being immunized. We used modified Poisson regression to estimate the prevalence ratio (PR) of influenza immunization for health care occupations compared with the general working population.For all survey cycles combined, 50% of 18?446 health care personnel reported receiving seasonal influenza immunization during the previous 12 months, although this varied by occupation type (range 4%-72%). Compared with the general working population, family physicians and general practitioners were most likely to be immunized (PR 3.15, 95% confidence interval [CI] 2.76-3.59), whereas chiropractors, midwives and practitioners of natural healing were least likely (PR 0.17, 95% CI 0.10-0.30). Among those who were not immunized, the most frequently cited reason was the belief that influenza immunization is unnecessary. Introduction of vaccinate-or-mask policies was associated with increased influenza immunization among health care personnel.Health care personnel are more likely to be immunized against influenza than the general working population, but coverage remains suboptimal overall, and we observed wide variation by occupation type. More efforts are needed to target specific health care occupations with low immunization coverage.
| S-EPMC5047845 | biostudies-other
Project description:Influenza virus causes widespread, yearly epidemics by accumulating surface protein mutations to escape neutralizing antibodies established from prior exposure. In contrast to antibody epitopes, T cell mediated immunity targets influenza epitopes that are more highly conserved and have potential for cross-protection. The extent of T cell cross-reactivity between a diverse array of contemporary and historical influenza strains was investigated in ferrets challenged with 2009 pandemic H1N1 influenza or the seasonal H3N2 strain, A/Perth/16/2009. Post-challenge cell-mediated immune responses demonstrated extensive cross-reactivity with a wide variety of contemporary and historical influenza A strains as well as influenza B. Responses in peripheral blood were undetectable by 36d post-challenge, but cross-reactivity persisted in spleen. The strongest responses targeted peptides from the NP protein and demonstrated cross-reactivity in both the CD4+ and CD8+ T cell populations. Cross-reactive CD4+ T cells also targeted HA and NA epitopes, while cross-reactive CD8+ T cells targeted internal M1, NS2, and PA. T cell epitopes demonstrated extensive cross-reactivity between diverse influenza strains in outbred animals, with NP implicated as a significant antigenic target demonstrating extensive cross-reactivity for both CD4+ and CD8+ T cells.
| S-EPMC5904180 | biostudies-literature
Project description:Different vaccine strains included in the live attenuated influenza vaccine (LAIV) have variable efficacy. The reasons for this are not clear and may include differences in immunogenicity. We report a Phase IV open-label study on the immunogenicity of a single dose of quadrivalent LAIV (Fluenz™ Tetra) in children during the 2015/16 season, to investigate the antibody responses to different strains. Eligible children were enrolled to receive LAIV; nasal samples were collected before and approximately 4 weeks after immunization. There was a significant increase in nasal immunoglobulin (Ig)A to the H3N2, B/Victoria lineage (B/Brisbane) and B/Yamagata lineage (B/Phuket) components, but not to the H1N1 component. The fold change in nasal IgA response was inversely proportional to the baseline nasal IgA titre for H1N1, H3N2 and B/Brisbane. We investigated possible associations that may explain baseline nasal IgA, including age and prior vaccination status, but found different patterns for different antigens, suggesting that the response is multi-factorial. Overall, we observed differences in immune responses to different viral strains included in the vaccine; the reasons for this require further investigation.
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Project description:There is mounting evidence that in the absence of neutralizing antibodies cross-reactive T cells provide protection against pandemic influenza viruses. Here, we compared protection and CD8+ T cell responses following challenge with H1N1 2009 pandemic and H3N2 viruses of mice that had been immunized with hemagglutinin (HA), neuraminidase (NA) and the extracellular domain of matrix protein 2 (M2e) fused to a virus-like particle (VLP). Mice were challenged a first time with a sublethal dose of H1N1 2009 pandemic virus and, four weeks later, challenged again with an H3N2 virus. Mice that had been vaccinated with HA, NA, NA + M2e-VLP and HA + NA + M2e-VLP were protected against homologous H1N1 virus challenge. Challenged NA and NA + M2e-VLP vaccinated mice mounted CD8+ T cell responses that correlated with protection against secondary H3N2 challenge. HA-vaccinated mice were fully protected against challenge with homologous H1N1 2009 virus, failed to mount cross-reactive CD8+ T cells and succumbed to the second challenge with heterologous H3N2 virus. In summary, NA- and M2e-based immunity can protect against challenge with (homologous) virus without compromising the induction of robust cross-reactive CD8+ T cell responses upon exposure to virus.
| S-EPMC4829898 | biostudies-literature
Project description:The Public Health Agency of Canada recommends that 80% of high-risk persons, including adults aged ≥65 years and 18–64 years with certain comorbidities, be vaccinated against influenza. During the 2022–2023 influenza season, we conducted an online survey of 3000 Canadian residents aged ≥18 years randomly recruited from the Léger Opinion (LEO) consumer panel to assess knowledge and perceptions about influenza vaccination as well as survey self-reported vaccination rates. Overall, 47.3% received an influenza vaccination during the 2022–2023 season. Vaccination rates among persons aged 18–64 years with high-risk medical conditions (n = 686) and among adults aged ≥65 years (n = 708) were 46.4% and 77.4%, respectively; 77.8% and 88.5%, respectively, believed influenza vaccination was important for people at high risk from influenza. Only 35.8% of adults aged 18–64 years with comorbidities were aware of being at high risk; 66.0% of this group was vaccinated against influenza, compared with 37.0% of those unaware of being at high-risk. During 2022–2023, 51.3% of people aged ≥65 years and 43.0% of people aged 18–64 years with comorbidities discussed influenza vaccination with healthcare providers. These findings suggest gaps in education regarding the importance of influenza vaccination among people at risk of influenza complications.
| S-EPMC10459598 | biostudies-literature
Project description:Previously, we constructed a chimeric influenza virus that expresses the highly conserved amino acid sequence ELDKWA of gp41 of human immunodeficiency virus type 1 (HIV-1). Antisera elicited in mice by infection with this chimeric virus showed neutralizing activity against distantly related HIV-1 isolates (T. Muster, R. Guinea, A. Trkola, M. Purtscher, A. Klima, F. Steindl, P. Palese, and H. Katinger, J. Virol. 68:4031-4034, 1994). In the present study, we demonstrated that intranasal immunizations with this chimeric virus are also able to induce a humoral immune response at the mucosal level. The immunized mice had ELDKWA-specific immunoglobulins A in respiratory, intestinal, and vaginal secretions. Sustained levels of these secretory immunoglobulins A were detectable for more than 1 year after immunization. The results show that influenza virus can be used to efficiently induce secretory antibodies against antigens from foreign pathogens. Since long-lasting mucosal immunity in the genital and intestinal tracts might be essential for protective immunity against HIV-1, influenza virus appears to be a promising vector for HIV-1-derived immunogens.
| S-EPMC189577 | biostudies-other
Project description:BackgroundThe live-attenuated Japanese encephalitis (JE) vaccine (JE-CV; IMOJEV) induces a protective response in children. A shift in circulating JE virus strains suggests that a genotype shift phenomenon may occur throughout Southeast Asia. We assessed the neutralization of wild-type (WT) JE virus isolates at distal time points after vaccination.MethodsWe analyzed serum samples from a subset of 47 children who had received a JE-CV booster after an inactivated JE vaccine primary immunization. We measured antibody titers (50% plaque reduction neutralization test) using a panel of WT JE strains at baseline, then after the booster at 28 days and 6 months in all subjects present at the time points and in a subset at year 5. Three additional recent isolates were tested at year 5.ResultsOf 47 subjects, 43 (91.5%) subjects had JE neutralizing antibody titers ≥10 (reciprocal serum dilution) against the homologous strain before JE-CV boost; all were seroprotected up to year 5 after the JE-CV boost. Baseline WT seroprotection ranged between 78.7% and 87.2%; all subjects were seroprotected against the 4 WT strains at 28 days and 6 months; year 5 seroprotection ranged between 95.7% and 97.9%. Similar rates of protection against 3 additional WT isolates were observed at year 5.ConclusionsThe long-term immune responses induced after a JE-CV booster dose in toddlers were able to neutralize WT viruses from various genotypes circulating in Southeast Asia and India.Clinical trials registrationNCT00621764.
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Project description:BackgroundThis costing study in Malawi is a first evaluation of a Maternal Influenza Immunization Program Costing Tool (Costing Tool) for maternal immunization. The tool was designed to help low- and middle-income countries plan for maternal influenza immunization programs that differ from infant vaccination programs because of differences in the target population and potential differences in delivery strategy or venue.MethodsThis analysis examines the incremental costs of a prospective seasonal maternal influenza immunization program that is added to a successful routine childhood immunization and antenatal care program. The Costing Tool estimates financial and economic costs for different vaccine delivery scenarios for each of the major components of the expanded immunization program.ResultsIn our base scenario, which specifies a donated single dose pre-filled vaccine formulation, the total financial cost of a program that would reach 2.3 million women is approximately $1.2 million over five years. The economic cost of the program, including the donated vaccine, is $10.4 million over the same period. The financial and economic costs per immunized pregnancy are $0.52 and $4.58, respectively. Other scenarios examine lower vaccine uptake, reaching 1.2 million women, and a vaccine purchased at $2.80 per dose with an alternative presentation.ConclusionThis study estimates the financial and economic costs associated with a prospective maternal influenza immunization program in a low-income country. In some scenarios, the incremental delivery cost of a maternal influenza immunization program may be as low as some estimates of childhood vaccination programs, assuming the routine childhood immunization and antenatal care systems are capable of serving as the platform for an additional vaccination program. However, purchasing influenza vaccines at the prices assumed in this analysis, instead of having them donated, is likely to be challenging for lower-income countries. This result should be considered as a starting point to understanding the costs of maternal immunization programs in low- and middle-income countries.
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Project description:Newly-emerged and vaccine-mismatched influenza A viruses (IAVs) result in a rapid global spread of the virus due to minimal antibody-mediated immunity. In that case, established CD8+ T-cells can reduce disease severity. However, as mutations occur sporadically within immunogenic IAV-derived T-cell peptides, understanding of T-cell receptor (TCR??) cross-reactivity towards IAV variants is needed for a vaccine design. Here, we investigate TCR?? cross-strain recognition across IAV variants within two immunodominant human IAV-specific CD8+ T-cell epitopes, HLA-B*37:01-restricted NP338-346 (B37-NP338) and HLA-A*01:01-restricted NP44-52 (A1-NP44). We find high abundance of cross-reactive TCR?? clonotypes recognizing distinct IAV variants. Structures of the wild-type and variant peptides revealed preserved conformation of the bound peptides. Structures of a cross-reactive TCR-HLA-B37-NP338 complex suggest that the conserved conformation of the variants underpins TCR cross-reactivity. Overall, cross-reactive CD8+ T-cell responses, underpinned by conserved epitope structure, facilitates recognition of distinct IAV variants, thus CD8+ T-cell-targeted vaccines could provide protection across different IAV strains.
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Project description:The development of a universal influenza vaccine is an ideal strategy to eliminate public health threats from influenza epidemics and pandemics. This ultimate goal is restricted by the low immunogenicity of conserved influenza epitopes. Layered protein nanoparticles composed of well-designed conserved influenza structures have shown improved immunogenicity with new physical and biochemical features. Herein, structure-stabilized influenza matrix protein 2 ectodomain (M2e) and M2e-neuraminidase fusion (M2e-NA) recombinant proteins are generated and M2e protein nanoparticles and double-layered M2e-NA protein nanoparticles are produced by ethanol desolvation and chemical crosslinking. Immunizations with these protein nanoparticles induce immune protection against different viruses of homologous and heterosubtypic NA in mice. Double-layered M2e-NA protein nanoparticles induce higher levels of humoral and cellular responses compared with their comprising protein mixture or M2e nanoparticles. Strong cytotoxic T cell responses are induced in the layered M2e-NA protein nanoparticle groups. Antibody responses contribute to the heterosubtypic NA immune protection. The protective immunity is long lasting. These results demonstrate that double-layered protein nanoparticles containing structure-stabilized M2e and NA can be developed into a universal influenza vaccine or a synergistic component of such vaccines. Layered protein nanoparticles can be a general vaccine platform for different pathogens.
| S-EPMC6980908 | biostudies-literature