scholarly journals Effects of Prior Influenza Exposure on Immunogenicity of Influenza Vaccine

2020 ◽  
Author(s):  
Jia-Qian Cao ◽  
Peng-Fei Jin ◽  
Zhao-Zhun Zeng ◽  
Li Zhang ◽  
Fan-Yue Meng ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Influenza Virus ◽  
Immune Responses ◽  
Influenza Vaccine ◽  
Hemagglutination Inhibition ◽  
Cross Reactivity ◽  
Vaccine Effectiveness ◽  
Prior Exposure ◽  
Post Vaccination ◽  
Blood Samples

Abstract Background To investigate effects of prior influenza exposure on vaccine-elicited humor immune responses to circulating influenza variants. Method We randomly selected 360 participants in previous clinical trials stratified by age. Blood samples before and 28 days after vaccination were collected and tested by hemagglutination-inhibition tests against both vaccine strains and circulating variants during the 2015–2016 influenza seasons in China. The antigenic map was plotted and antigenic distance was calculated. Results Subjects with H1-priming had higher cross-reactive antibodies titers against A/JiangsuTinghu/11019/2015(H3N2) compared with subjects with B-priming did (Padjusted=0.038). Subjects with H1-priming also had higher cross-reactive antibodies titers against A/Jiangsu Qinhuai/11059/2015(H3N2) than subjects with both H1 and B priming did (Padjusted=0.036). Nevertheless, subjects with no H1 and B-priming had higher cross-reactive antibodies titers against A/Jiangsu Qinhuai/11059/2015(H3N2) than subjects with both H1 and B priming did (Padjusted=0.012). Antigenic distance was well-matched with serological results. Besides, age-specific differences in human post-vaccination responses against the identical circulating strain was noted. And children had most cross-reactive response to both H3N2 and B-yamagata subtypes. Conclusion Our results suggest that prior exposure to H1 or B influenza virus may influence cross-reactivity of H3-specific post-vaccination responses and consequently could influence the vaccine effectiveness. Our findings also support that there are age-specific differences in human post-vaccination responses.

scholarly journals 992. 2016–2017 Influenza Burden of Disease and End-of-Season Influenza Vaccine Effectiveness (VE) Estimates for Preventing Influenza-Related Hospitalization Among Canadian Adults: An Analysis From the Canadian Immunization Research Network (CIRN) Serious Outcomes Surveillance (SOS) Network

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S293-S294
Author(s):  
Michaela Nichols ◽  
Melissa K Andrew ◽  
Todd F Hatchette ◽  
Ardith Ambrose ◽  
Guy Boivin ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Influenza Vaccine ◽  
Active Surveillance ◽  
Burden Of Disease ◽  
Influenza A ◽  
Conditional Logistic Regression ◽  
Vaccine Effectiveness ◽  
Research Network ◽  
Nasopharyngeal Swab ◽  
Research Grant

Abstract Background To inform public health decision making around influenza prevention and treatment, ongoing surveillance of the influenza burden of disease and assessment of influenza vaccine effectiveness (VE) is critical. The Canadian Immunization Research Network (CIRN) Serious Outcomes Surveillance (SOS) Network conducts active surveillance each influenza season to characterize the burden of influenza disease and to provide estimates of influenza VE to prevent influenza-related hospitalization in Canadian adults (≥16 years of age). Methods Active surveillance for influenza was conducted at 13 hospitals in four provinces beginning on November 15, 2016 and ending April 30, 2017. Patients admitted with any respiratory diagnosis or symptom were eligible for enrolment. Eligible patients had a nasopharyngeal swab collected and tested for influenza using polymerase chain reaction (PCR). Patients who tested positive for influenza were considered cases; patients who tested negative for influenza were eligible to become matched controls. Detailed demographic and medical information were obtained from the medical record. Influenza VE was estimated as 1 − odds ratio (OR) of influenza in vaccinated vs. unvaccinated patients × 100% using conditional logistic regression, with corresponding 95% confidence intervals (CIs). Results A total of 1,431 influenza cases were enrolled; the majority were influenza A (n = 1,299) and 100% of patients with known influenza A subtype were A/H3N2. Among all influenza cases, 144 (10.1%) patients were admitted to the intensive care unit (ICU) and 91 (6.4%) patients died within 30 days of discharge. Overall adjusted influenza VE for prevention of influenza-related hospitalization in all ages was 23.3% (95% CI: 2.9–39.4%), with slightly lower VE observed in patients ≥65 years (VE: 19.4%; 95% CI: −7.8–39.8%) and higher VE observed in patients <65 years (VE: 47.9%; 95% CI: 9.9–69.9%). Conclusion Overall, influenza VE was low but effective (VE: 23%) for preventing influenza-related hospitalization during the 2016–2017 season in Canada. Given the low influenza VE observed, continued assessment of influenza VE is crucial to inform immunization policy in Canada and to emphasize the importance of the development and utilization of improved influenza vaccines. Disclosures M. K. Andrew, GSK: Grant Investigator, Research grant. Pfizer: Grant Investigator, Research grant. sanofi pasteur: Grant Investigator, Research grant. T. F. Hatchette, GSK: Grant Investigator, Research grant. Pfizer: Grant Investigator, Research grant. Abbvie: Consultant, Speaker honorarium. J. McElhaney, GSK: Scientific Advisor, Speaker honorarium. sanofi pasteur: Scientific Advisor, Speaker honorarium. A. McGeer, GSK: Grant Investigator, Research grant. Hoffman La Roche: Grant Investigator, Research grant. sanofi pasteur: Grant Investigator, Research grant. A. Poirier, sanofi pasteur: Investigator, Research grant. Actelion: Grant Investigator, Research grant. J. Powis, GSK: Grant Investigator, Research grant. Merck: Grant Investigator, Research grant. Roche: Grant Investigator, Research grant. Synthetic Biologics: Investigator, Grant recipient. M. Semret, GSK: Grant Investigator, Research grant. Pfizer: Grant Investigator, Research grant. S. Trottier, CIHR: Grant Investigator, Research grant. S. A. McNeil, GSK: Grant Investigator, Research grant. Pfizer: Grant Investigator, Research grant. Merck: Collaborator and Consultant, Contract clinical trials and Speaker honorarium. Novartis: Collaborator, Contract clinical trials. sanofi pasteur: Collaborator, Contract clinical trials.

scholarly journals Preexisting Immunity, More Than Aging, Influences Influenza Vaccine Responses

2015 ◽  
Vol 2 (2) ◽  
Author(s):  
Adrian J. Reber ◽  
Jin Hyang Kim ◽  
Renata Biber ◽  
H. Keipp Talbot ◽  
Laura A. Coleman ◽  
...  
Keyword(s):  
Older Adults ◽  
B Cells ◽  
Immune Responses ◽  
Influenza Vaccine ◽  
Hemagglutination Inhibition ◽  
Negative Impact ◽  
Memory B Cells ◽  
Vaccine Response ◽  
Vaccine Responses ◽  
Antibody Levels

Abstract Background.  Influenza disproportionately impacts older adults while current vaccines have reduced effectiveness in the older population. Methods.  We conducted a comprehensive evaluation of cellular and humoral immune responses of adults aged 50 years and older to the 2008–2009 seasonal trivalent inactivated influenza vaccine and assessed factors influencing vaccine response. Results.  Vaccination increased hemagglutination inhibition and neutralizing antibody; however, 66.3% of subjects did not reach hemagglutination inhibition titers ≥ 40 for H1N1, compared with 22.5% for H3N2. Increasing age had a minor negative impact on antibody responses, whereas prevaccination titers were the best predictors of postvaccination antibody levels. Preexisting memory B cells declined with age, especially for H3N2. However, older adults still demonstrated a significant increase in antigen-specific IgG+ and IgA+ memory B cells postvaccination. Despite reduced frequency of preexisting memory B cells associated with advanced age, fold-rise in memory B cell frequency in subjects 60+ was comparable to subjects age 50–59. Conclusions.  Older adults mounted statistically significant humoral and cell-mediated immune responses, but many failed to reach hemagglutination inhibition titers ≥40, especially for H1N1. Although age had a modest negative effect on vaccine responses, prevaccination titers were the best predictor of postvaccination antibody levels, irrespective of age.

scholarly journals Influenza Vaccine Effectiveness in the Netherlands from 2003/2004 through 2013/2014: The Importance of Circulating Influenza Virus Types and Subtypes

PLoS ONE ◽  
2017 ◽  
Vol 12 (1) ◽  
pp. e0169528 ◽  
Author(s):  
Maryam Darvishian ◽  
Frederika Dijkstra ◽  
Eva van Doorn ◽  
Maarten J. Bijlsma ◽  
Gé A. Donker ◽  
...  
Keyword(s):  
Influenza Virus ◽  
The Netherlands ◽  
Influenza Vaccine ◽  
Vaccine Effectiveness

scholarly journals No Effect of Acute Eccentric Resistance Exercise on Immune Responses to Influenza Vaccination in Older Adults: A Randomized Control Trial

2021 ◽  
Vol 12 ◽  
Author(s):  
Mahmoud T. Elzayat ◽  
Melissa M. Markofski ◽  
Richard J. Simpson ◽  
Mitzi Laughlin ◽  
Emily C. LaVoy
Keyword(s):  
Older Adults ◽  
T Cells ◽  
Immune Responses ◽  
Influenza Vaccine ◽  
Resistance Exercise ◽  
Influenza Vaccination ◽  
Intracellular Cytokine Staining ◽  
Significant Group ◽  
Post Vaccination ◽  
Antibody Titers

IntroductionOlder adults are at elevated risk for morbidity and mortality caused by influenza. Vaccination is the primary means of prophylaxis, but protection is often compromised in older adults. As resistance exercise mobilizes immune cells into muscle, it may enhance vaccination response.PurposeCompare antibody and cell mediated immune responses to influenza vaccination in older adults who performed eccentric resistance exercise immediately prior to vaccination to those who did not exercise.MethodsTwenty nine resistance training-naive older adults (20 women, 73.9 ± 5.3 years) were randomized to 1 of 3 groups: vaccination in the same arm that exercised (Ex-S), vaccination in the opposite arm that exercised (Ex-Op), and seated rest (No-Ex). Exercise consisted of 10 sets of 5 eccentric unilateral repetitions at 80% of the pre-determined concentric one repetition maximum. Lateral raises were alternated with bicep curls. No-Ex sat quietly for 25 min. Following exercise or rest, all received the 2018 quadrivalent influenza vaccine (Seqirus Afluria) in the non-dominant deltoid. Antibody titers against each influenza vaccine strain were determined by hemagglutinin inhibition assays at baseline, 6-, and 24-weeks post-vaccination. Influenza-specific T cells were quantified after stimulation with the vaccine by intracellular cytokine staining.ResultsNo significant group x time effects were found in antibody responses to any strain (interaction for A/H1N1: p = 0.682; A/H3N2: p = 0.644; B/Colorado/06/2017: p = 0.262; B/Phuket/3073/2013: p = 0.851). Groups did not differ in fold-increase of antibody titers 6- and 24-weeks post-vaccination. Influenza-specific T-cells did not differ between groups at any time (comparison at baseline: p = 0.985; 6-weeks: p = 0.889; 24 weeks: p = 0.857). One subject (Ex-S) reported flu-like symptoms 18 weeks post-vaccination.ConclusionAcute arm eccentric exercise did not influence antibody titers or cell mediated immune responses to the influenza vaccine delivered post-exercise in older adults. More strenuous exercise may be required for exercise to act as an adjuvant. ClinicalTrials.gov Identifier: NCT03736759.

scholarly journals Key Determinants of Cell-Mediated Immune Responses: A Randomized Trial of High Dose Vs. Standard Dose Split-Virus Influenza Vaccine in Older Adults

2021 ◽  
Vol 2 ◽  
Author(s):  
Chris P. Verschoor ◽  
Laura Haynes ◽  
Graham Pawelec ◽  
Mark Loeb ◽  
Melissa K. Andrew ◽  
...  
Keyword(s):  
Older Adults ◽  
Immune Responses ◽  
Influenza Vaccine ◽  
Influenza A ◽  
Standard Dose ◽  
Serum Antibody ◽  
High Dose ◽  
Post Vaccination ◽  
Antibody Titers ◽  
Virus Influenza

Background: Efforts to improve influenza vaccine effectiveness in older adults have resulted in some successes, such as the introduction of high-dose split-virus influenza vaccine (HD-SVV), yet studies of cell-mediated immune responses to these vaccines remain limited. We have shown that granzyme B (GrB) activity in influenza A/H3N2 challenged peripheral blood mononuclear cells (PBMC) correlates with protection against influenza following standard dose vaccination (SD-SVV) in older adults. Further, the interferon-γ (IFNγ) to interleukin-10 (IL-10) ratio can be a correlate of protection.Methods: In a double-blind trial (ClinicalTrials.gov NCT02297542) older adults (≥65 years, n = 582) were randomized to receive SD-SVV or HD-SVV (Fluzone®) from 2014/15 to 2017/18. Young adults (20–40 years, n = 79) received SD-SVV. At 0, 4, 10, and 20 weeks post-vaccination, serum antibody titers, IFNγ, IL-10, and inducible GrB (iGrB) were measured in ex vivo influenza-challenged PBMC. iGrB is defined as the fold change in GrB activity from baseline levels (bGrB) in circulating T cells. Responses of older adults were compared to younger controls, and in older adults, we analyzed effects of age, sex, cytomegalovirus (CMV) serostatus, frailty, and vaccine dose.Results: Prior to vaccination, younger compared to older adults produced significantly higher IFNγ, IL-10, and iGrB levels. Relative to SD-SVV recipients, older HD-SVV recipients exhibited significantly lower IFNγ:IL-10 ratios at 4 weeks post-vaccination. In contrast, IFNγ and iGrB levels were higher in younger SD vs. older SD or HD recipients; only the HD group showed a significant IFNγ response to vaccination compared to the SD groups; all three groups showed a significant iGrB response to vaccination. In a regression analysis, frailty was associated with lower IFNγ levels, whereas female sex and HD-SVV with higher IL-10 levels. Age and SD-SVV were associated with lower iGrB levels. The effect of prior season influenza vaccination was decreased iGrB levels, and increased IFNγ and IL-10 levels, which correlated with influenza A/H3N2 hemagglutination inhibition antibody titers.Conclusion: Overall, HD-SVV amplified the IL-10 response consistent with enhanced antibody responses, with little effect on the iGrB response relative to SD-SVV in either younger or older adults. These results suggest that enhanced protection with HD-SVV is largely antibody-mediated.Clinical Trial Registration: ClinicalTrials.gov (NCT02297542).

scholarly journals Estimating Vaccine Effectiveness Against Hospitalized Influenza During Pregnancy: Multicountry Protocol for a Retrospective Cohort Study (Preprint)

2018 ◽  
Author(s):  
Allison L Naleway ◽  
Sarah Ball ◽  
Jeffrey C Kwong ◽  
Brandy E Wyant ◽  
Mark A Katz ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Influenza Vaccine ◽  
Influenza Vaccination ◽  
Pregnant Women ◽  
Retrospective Cohort ◽  
Clinical Course ◽  
Influenza Virus Infection ◽  
The United States ◽  
Vaccine Effectiveness

BACKGROUND Although pregnant women are believed to have elevated risks of severe influenza infection and are targeted for influenza vaccination, no study to date has examined influenza vaccine effectiveness (IVE) against laboratory-confirmed influenza-associated hospitalizations during pregnancy, primarily because this outcome poses many methodological challenges. OBJECTIVE The Pregnancy Influenza Vaccine Effectiveness Network (PREVENT) was formed in 2016 as an international collaboration with the Centers for Disease Control and Prevention; Abt Associates; and study sites in Australia, Canada, Israel, and the United States. The primary goal of this collaboration is to estimate IVE in preventing acute respiratory or febrile illness (ARFI) hospitalizations associated with laboratory-confirmed influenza virus infection during pregnancy. Secondary aims include (1) describing the incidence, clinical course, and severity of influenza-associated ARFI hospitalization during pregnancy; (2) comparing the characteristics of ARFI-hospitalized pregnant women who were tested for influenza with those who were not tested; (3) describing influenza vaccination coverage in pregnant women; and (4) comparing birth outcomes among women with laboratory-confirmed influenza-associated hospitalization versus other noninfluenza ARFI hospitalizations. METHODS For an initial assessment of IVE, sites identified a retrospective cohort of pregnant women aged from 18 to 50 years whose pregnancies overlapped with local influenza seasons from 2010 to 2016. Pregnancies were defined as those that ended in a live birth or stillbirth of at least 20 weeks gestation. The analytic sample for the primary IVE analysis was restricted to pregnant women who were hospitalized for ARFI during site-specific influenza seasons and clinically tested for influenza virus infection using real-time reverse transcription polymerase chain reaction. RESULTS We identified approximately 2 million women whose pregnancies overlapped with influenza seasons; 550,344 had at least one hospitalization during this time. After restricting to women who were hospitalized for ARFI and tested for influenza, the IVE analytic sample included 1005 women. CONCLUSIONS In addition to addressing the primary question about the effectiveness of influenza vaccination, PREVENT data will address other important knowledge gaps including understanding the incidence, clinical course, and severity of influenza-related hospitalizations during pregnancy. The data infrastructure and international partnerships created for these analyses may be useful and informative for future influenza studies. INTERNATIONAL REGISTERED REPOR DERR1-10.2196/11333

scholarly journals Immunogenicity and Cross Protection in Mice Afforded by Pandemic H1N1 Live Attenuated Influenza Vaccine Containing Wild-Type Nucleoprotein

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Andrey Rekstin ◽  
Irina Isakova-Sivak ◽  
Galina Petukhova ◽  
Daniil Korenkov ◽  
Igor Losev ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Immune Responses ◽  
Influenza Vaccine ◽  
Wild Type Virus ◽  
Pandemic H1n1 ◽  
Type Virus ◽  
Wild Type ◽  
Live Attenuated Influenza Vaccine ◽  
Np Gene

Since conserved viral proteins of influenza virus, such as nucleoprotein (NP) and matrix 1 protein, are the main targets for virus-specific CD8+ cytotoxic T-lymphocytes (CTLs), we hypothesized that introduction of the NP gene of wild-type virus into the genome of vaccine reassortants could lead to better immunogenicity and afford better protection. This paper describes in vitro and in vivo preclinical studies of two new reassortants of pandemic H1N1 live attenuated influenza vaccine (LAIV) candidates. One had the hemagglutinin (HA) and neuraminidase (NA) genes from A/South Africa/3626/2013 H1N1 wild-type virus on the A/Leningrad/134/17/57 master donor virus backbone (6 : 2 formulation) while the second had the HA, NA, and NP genes of the wild-type virus on the same backbone (5 : 3 formulation). Although both LAIVs induced similar antibody immune responses, the 5 : 3 LAIV provoked greater production of virus-specific CTLs than the 6 : 2 variant. Furthermore, the 5 : 3 LAIV-induced CTLs had higher in vivo cytotoxic activity, compared to 6 : 2 LAIV. Finally, the 5 : 3 LAIV candidate afforded greater protection against infection and severe illness than the 6 : 2 LAIV. Inclusion in LAIV of the NP gene from wild-type influenza virus is a new approach to inducing cross-reactive cell-mediated immune responses and cross protection against pandemic influenza.

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