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Sex-specific differences of humoral immunity and transcriptome diversification in older adults vaccinated with inactivated quadrivalent influenza vaccines.

ABSTRACT: Clinical data showed sex variability in the immune response to influenza vaccination, this study aimed to investigate differentially expressed genes (DEGs) that contribute to sex-bias immunity to quadrivalent inactivated influenza vaccines (QIVs) in the elderly. 60 healthy adults aged 60-80 yrs were vaccinated with QIVs, and gene expression was analyzed before and after vaccination. The humoral immunity was analyzed by HAI assay, and the correlation of gene expression patterns of two sex groups with humoral immunity was analyzed. The DEGs involved in type I interferon signaling pathway and complement activation of classical pathway were upregulated within 3 days in females. At Day 28, the immune response showed a male-bias pattern associated with the regulation of protein processing and complement activation of classical pathway. A list of DEGs associated with variant responses to influenza vaccination between females and males were identified by biology-driven clustering. Old females have a greater immune response to QIVs but a rapid antibody decline, while old males have the advantages to sustain a durable response. In addition, we identified genes that may contribute to the sex variations toward influenza vaccination in the aged. Our findings highlight the importance of developing personalized seasonal influenza vaccines.

SUBMITTER: Yang J

PROVIDER: S-EPMC8064175 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Sex-Specific Differences of Humoral Immunity and Transcriptome Diversification in Older Adults Vaccinated with Inactivated Quadrivalent Influenza Vaccines

Project description:Clinical data showed sex variability in the immune response to influenza vaccination, this study aimed to investigate differentially expressed genes that contribute to sex-bias immune responses to quadrivalent inactivated influenza vaccines (QIVs) in older subjects. A cohort of 60 healthy older adults aged 60 to 80 years old were vaccinated with quadrivalent inactivated influenza vaccines (QIVs), and gene expression was analyzed at Day 0 pre-vaccination, Day 3, Day 28 and Day 180 post-vaccination. Sexual dimorphism of humoral immunity was analyzed by HAI assay, and the correlation of gene expression patterns of two sex groups with humoral immune response to vaccination was analyzed. The differentially expressed genes involved in type I interferon signaling pathway and complement activation of classical pathway were upregulated within 3 days post-vaccination in females. At Day 28 after immunization, the immune response showed a man-bias pattern associated with the regulation of protein processing and complement activation of classical pathway. A list of differentially expressed genes associated with variant responses to influenza vaccination between women and men were identified by biology-driven clustering. Old women have a greater immune response to QIVs but rapid decline of antibody levels, while old men have the advantages to sustain a durable response to influenza vaccination. In addition, we identified genes that may contribute to the sex variations toward influenza vaccination in the aged. Our findings highlight the importance of developing personalized seasonal influenza vaccines.

2020-11-09 | GSE151558 | GEO

Sex-Specific Differences of Humoral Immunity and Transcriptome Diversification in Older Adults Vaccinated with Inactivated Quadrivalent Influenza Vaccines

Project description:Sex-Specific Differences of Humoral Immunity and Transcriptome Diversification in Older Adults Vaccinated with Inactivated Quadrivalent Influenza Vaccines

| PRJNA636362 | ENA

Cost Effectiveness of Quadrivalent Versus Trivalent Inactivated Influenza Vaccines for the Portuguese Elderly Population.

Project description:Backgroundquadrivalent inactivated vaccine (QIV) has replaced trivalent inactivated vaccine (TIV). In Portugal, TIV is free of charge for risk groups, including older adults (≥65 years old). In its turn, QIV-which provides broader protection as it includes an additional lineage B strain-was introduced in Portugal in October 2018; only since the 2019/20 influenza season has it been provided free of charge for risk groups. This study evaluates the cost effectiveness of switching from TIV to QIV, from the National Health Service perspective, in the Portuguese elderly mainland population.MethodsA decision tree model was developed to compare TIV and QIV, based on Portuguese hospitalization data for the 2015/16 influenza season. The primary health economic outcome under consideration was the incremental cost-effectiveness ratio (ICER). In addition, one-way sensitivity analysis and probabilistic sensitivity analysis were performed.Resultsthe high cost of QIV (approximately three times the cost of TIV) would lead to a total increment of EUR 5,283,047, and the resulting ICER would be EUR 26,403,007/QALY, above the usual willingness-to-pay threshold.Conclusionsfrom the National Health Service perspective, our findings reveal that QIV is not cost effective for the Portuguese elderly population due to the high cost. If the QIV costs were the same as the TIV, then QIV would be cost effective.

| S-EPMC9416623 | biostudies-literature

Switching from trivalent to quadrivalent inactivated influenza vaccines in Uruguay: a cost-effectiveness analysis.

Project description:We evaluated the cost-utility of replacing trivalent influenza vaccine (TIV) with quadrivalent influenza vaccine (QIV) in the current target populations in Uruguay. An existing decision-analytic static cost-effectiveness model was adapted for Uruguay. The population was stratified into age groups. Costs and outcomes were estimated for an average influenza season, based on observed rates from 2013 to 2019 inclusive. Introducing QIV instead of TIV in Uruguay would avoid around 740 additional influenza cases, 500 GP consultations, 15 hospitalizations, and three deaths, and save around 300 workdays, for the same vaccination coverage during an average influenza season. Most of the influenza-related consultations and hospitalizations would be avoided among children ≤4 and adults ≥65 years of age. Using QIV rather than TIV would cost an additional ~US$729,000, but this would be partially offset by savings in consultations and hospitalization costs. The incremental cost per quality-adjusted life-year (QALY) gained with QIV would be in the order of US$18,000 for both the payor and societal perspectives, for all age groups, and around US$12,000 for adults ≥65 years of age. The main drivers influencing the incremental cost-effectiveness ratio were the vaccine efficacy against the B strains and the percentage of match each season with the B strain included in TIV. Probabilistic sensitivity analysis showed that switching to QIV would provide a favorable cost-utility ratio for 50% of simulations at a willingness-to-pay per QALY of US$20,000. A switch to QIV is expected to be cost-effective for the current target populations in Uruguay, particularly for older adults.

| S-EPMC9225211 | biostudies-literature

The rationale for quadrivalent influenza vaccines.

Project description:Two antigenically distinct lineages of influenza B viruses have circulated globally since 1985. However, licensed trivalent seasonal influenza vaccines contain antigens from only a single influenza B virus and thus provide limited immunity against circulating influenza B strains of the lineage not present in the vaccine. In recent years, predictions about which B lineage will predominate in an upcoming influenza season have been no better than chance alone, correct in only 5 of the 10 seasons from 2001 to 2011. Consequently, seasonal influenza vaccines could be improved by inclusion of influenza B strains of both lineages. The resulting quadrivalent influenza vaccines would allow influenza vaccination campaigns to respond more effectively to current global influenza epidemiology. Manufacturing capacity for seasonal influenza vaccines has increased sufficiently to supply quadrivalent influenza vaccines, and methods to identify the influenza B strains to include in such vaccines are in place. Multiple manufacturers have initiated clinical studies of quadrivalent influenza vaccines. Data from those studies, taken together with epidemiologic data regarding the burden of disease caused by influenza B infections, will determine the safety, effectiveness, and benefit of utilizing quadrivalent vaccines for the prevention of seasonal influenza disease.

| S-EPMC3350141 | biostudies-other

Relative Effectiveness of the Cell-derived Inactivated Quadrivalent Influenza Vaccine Versus Egg-derived Inactivated Quadrivalent Influenza Vaccines in Preventing Influenza-related Medical Encounters During the 2018-2019 Influenza Season in the United States.

Project description:BackgroundThe cell-propagated inactivated quadrivalent influenza vaccine (ccIIV4) may offer improved protection in seasons where egg-derived influenza viruses undergo mutations that affect antigenicity. This study estimated the relative vaccine effectiveness (rVE) of ccIIV4 versus egg-derived inactivated quadrivalent influenza vaccine (eIIV4) in preventing influenza-related medical encounters in the 2018-2019 US season.MethodsA dataset linking primary care electronic medical records with medical claims data was used to conduct a retrospective cohort study among individuals ≥ 4 years old vaccinated with ccIIV4 or eIIV4 during the 2018-2019 season. Adjusted odds ratios (ORs) were derived from a doubly robust inverse probability of treatment-weighted approach adjusting for age, sex, race, ethnicity, geographic region, vaccination week, and health status. rVE was estimated by (1 - OR) × 100 and presented with 95% confidence intervals (CI).ResultsFollowing the application of inclusion/exclusion criteria, the study cohort included 2 125 430 ccIIV4 and 8 000 903 eIIV4 recipients. Adjusted analyses demonstrated a greater reduction in influenza-related medical encounters with ccIIV4 versus eIIV4, with the following rVE: overall, 7.6% (95% CI, 6.5-8.6); age 4-17 years, 3.9% (95% CI, .9-7.0); 18-64 years, 6.5% (95% CI, 5.2-7.9); 18-49 years, 7.5% (95% CI, 5.7-9.3); 50-64 years, 5.6% (95% CI, 3.6-7.6); and ≥65 years, -2.2% (95% CI, -5.4 to .9).ConclusionsAdjusted analyses demonstrated statistically significantly greater reduction in influenza-related medical encounters in individuals vaccinated with ccIIV4 versus eIIV4 in the 2018-2019 US influenza season. These results support ccIIV4 as a potentially more effective public health measure against influenza than an egg-based equivalent.

| S-EPMC8326580 | biostudies-literature

Determination of influenza B identity and potency in quadrivalent inactivated influenza vaccines using lineage-specific monoclonal antibodies.

Project description:Co-circulation of two antigenically and genetically distinct lineages of influenza B virus, represented by prototype viruses B/Victoria/2/1987 and B/Yamagata/16/1988, has led to the development of quadrivalent influenza vaccines that contain two influenza B antigens. The inclusion of two influenza B antigens presents challenges for the production and regulation of inactivated quadrivalent vaccines, including the potential for cross-reactivity of the reagents used in identity and potency assays because of the relative close relatedness of the hemagglutinin (HA) from the two virus lineages. Monoclonal antibodies (mAbs) specific for the two lineages of influenza B HA were generated and characterized and used to set-up simple identity tests that distinguish the influenza B antigens in inactivated trivalent and quadrivalent vaccines. The lineage-specific mAbs bound well to the HA of influenza B strains included in influenza vaccines over a period of more than 10 years, suggesting that identity tests using such lineage-specific mAbs would not necessarily have to be updated with every influenza B vaccine strain change. These lineage-specific mAbs were also used in an antibody capture ELISA format to quantify HA in vaccine samples, including monovalent, trivalent, and quadrivalent vaccine samples from various manufacturers. The results demonstrated correlation with HA values determined by the traditional single radial immunodiffusion (SRID) assay. Further, the antibody-capture ELISA was able to distinguish heat-stressed vaccine from unstressed vaccine, and was similar to the SRID in quantifying the resultant loss of potency. These mAb reagents should be useful for further development of antibody-based alternative influenza B identity and potency assays.

| S-EPMC5396888 | biostudies-literature

Review of seasonal influenza in Canada: Burden of disease and the cost-effectiveness of quadrivalent inactivated influenza vaccines.

Project description:In the 2015/16 influenza season, the Canadian National Advisory Committee on Immunization (NACI) recommended vaccination with quadrivalent inactivated influenza vaccine (QIV) for infants aged 6-23 months and trivalent inactivated influenza vaccines (TIVs) or QIVs in adults. The objective of this review (GSK study identifier: HO-13-14054) is to examine the epidemiology and disease burden of influenza in Canada and the economic benefits of vaccination. To inform this review, we performed a systematic literature search of relevant Canadian literature and National surveillance data. Influenza B viruses from phylogenetically-distinct lineages (B/Yamagata and B/Victoria) co-circulate in Canada, and are an important cause of influenza complications. Modeling studies, including those postdating the search suggest that switching from TIV to QIV in Canada reduces the burden of influenza and would likely be cost-effective. However, more robust real-world outcomes data is required to inform health policy decision makers on appropriate influenza vaccination strategies for Canada.

| S-EPMC5404371 | biostudies-literature

Balanced Cellular and Humoral Immune Responses Targeting Multiple Antigens in Adults Receiving a Quadrivalent Inactivated Influenza Vaccine.

Project description:The role of T cell immunity has been acknowledged in recent vaccine development and evaluation. We tested the humoral and cellular immune responses to Flucelvax®, a quadrivalent inactivated seasonal influenza vaccine containing two influenza A (H1N1 Singapore/GP1908/2015 IVR-180 and H3N2 North Carolina/04/2016) and two influenza B (Iowa/06/2017 and Singapore/INFTT-16-0610/2016) virus strains, using peripheral blood mononuclear cells stimulated by pools of peptides overlapping all the individual influenza viral protein components. Baseline reactivity was detected against all four strains both at the level of CD4 and CD8 responses and targeting different proteins. CD4 T cell reactivity was mostly directed to HA/NA proteins in influenza B strains, and NP/M1/M2/NS1/NEP proteins in the case of the Influenza A strains. CD8 responses to both influenza A and B viruses preferentially targeted the more conserved core viral proteins. Following vaccination, both CD4 and CD8 responses against the various influenza antigens were increased in day 15 to day 91 post vaccination period, and maintained a Th1 polarized profile. Importantly, no vaccine interference was detected, with the increased responses balanced across all four included viral strains for both CD4 and CD8 T cells, and targeting HA and multiple additional viral antigens.

| S-EPMC8146362 | biostudies-literature

A randomized trial of candidate inactivated quadrivalent influenza vaccine versus trivalent influenza vaccines in children aged 3-17 years.

Project description:BackgroundTwo antigenically distinct influenza B lineages have cocirculated since 2001, yet trivalent influenza vaccines (TIVs) contain 1 influenza B antigen, meaning lineage mismatch with the vaccine is frequent. We assessed a candidate inactivated quadrivalent influenza vaccine (QIV) containing both B lineages vs TIV in healthy children aged 3-17 years.MethodsChildren were randomized 1:1:1 to receive QIV or 1 of 2 TIVs (either B/Victoria or B/Yamagata lineage; N = 2738). Hemagglutination-inhibition assays were performed 28 days after 1 or 2 doses in primed and unprimed children, respectively. Immunological noninferiority of QIV vs TIV against shared strains, and superiority against alternate-lineage B strains was based on geometric mean titers (GMTs) and seroconversion rates. Reactogenicity and safety were also assessed (Clinicaltrials.gov NCT01196988).ResultsNoninferiority against shared strains and superiority against alternate-lineage B strains was demonstrated for QIV vs TIV. QIV was highly immunogenic; seroconversion rates were 91.4%, 72.3%, 70.0%, and 72.5% against A/H1N1, A/H3N2, B/Victoria, and B/Yamagata, respectively. Reactogenicity and safety of QIV was consistent with TIV.ConclusionsQIV vs TIV showed superior immunogenicity for the additional B strain without interfering with immune responses to shared strains. QIV may offer improved protection against influenza B in children compared with current trivalent vaccines.

| S-EPMC3654742 | biostudies-literature

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