scholarly journals The Effect of Preexisting Immunity on Virus Detection and Immune Responses in a Phase II, Randomized Trial of a Russian-Backbone, Live, Attenuated Influenza Vaccine in Bangladeshi Children

2018 ◽  
Vol 69 (5) ◽  
pp. 786-794 ◽  
Author(s):  
Elizabeth B Brickley ◽  
Peter F Wright ◽  
Alexey Khalenkov ◽  
Kathleen M Neuzil ◽  
Justin R Ortiz ◽  
...  
Keyword(s):  
Immune Responses ◽  
Influenza Vaccine ◽  
Phase Ii ◽  
Influenza A ◽  
Virus Detection ◽  
Strain Differences ◽  
Potential Effect ◽  
Post Vaccination ◽  
Live Attenuated Influenza Vaccine ◽  
Bidirectional Association

Abstract Background In a 2012 Phase II clinical trial, 300 Bangladeshi children aged 24 to 59 months with no prior influenza vaccine exposure were randomized to receive a single intranasally-administered dose of either trivalent, Russian-backbone, live, attenuated influenza vaccine (LAIV) or placebo. Protocol-defined analyses, presented in the companion manuscript, demonstrate decreased viral detection and immunogenicity for A/H1N1pdm09, relative to the A/H3N2 and B strains. This post hoc analysis of the trial data aims to investigate the LAIV strain differences by testing the hypothesis that preexisting humoral and mucosal immunity may influence viral recovery and immune responses after LAIV receipt. Methods We used logistic regressions to evaluate the relations between markers of preexisting immunity (ie, hemagglutination inhibition [HAI], microneutralization, and immunoglobulin G and immunoglobulin A (both serum and mucosal antibodies) and LAIV viral recovery in the week post-vaccination. We then tested for potential effect modification by baseline HAI titers (ie, <10 versus ≥10) and week 1 viral recovery on the LAIV-induced serum and mucosal immune responses, measured between days 0 and 21 post-vaccination. Results Higher levels of preexisting immunity to influenza A/H3N2 and B were strongly associated with strain-specific prevention of viral shedding upon LAIV receipt. While evidence of LAIV immunogenicity was observed for all 3 strains, the magnitudes of immune responses were most pronounced in children with no evidence of preexisting HAI and in those with detectable virus. Conclusions The results provide evidence for a bidirectional association between viral replication and immunity, and underscore the importance of accounting for preexisting immunity when evaluating virologic and immunologic responses to LAIVs. Clinical Trials Registration NCT01625689.

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 Effectiveness of seasonal influenza vaccine for adults and children in preventing laboratory-confirmed influenza in primary care in the United Kingdom: 2015/16 end-of-season results

2016 ◽  
Vol 21 (38) ◽  
Author(s):  
Richard Pebody ◽  
Fiona Warburton ◽  
Joanna Ellis ◽  
Nick Andrews ◽  
Alison Potts ◽  
...  
Keyword(s):  
Primary Care ◽  
United Kingdom ◽  
Influenza Vaccine ◽  
Influenza A ◽  
Immunisation Programme ◽  
Influenza B ◽  
Live Attenuated Influenza Vaccine ◽  
The United Kingdom ◽  
Influenza A H1n1 ◽  
The Uk

The United Kingdom (UK) is in the third season of introducing universal paediatric influenza vaccination with a quadrivalent live attenuated influenza vaccine (LAIV). The 2015/16 season in the UK was initially dominated by influenza A(H1N1)pdm09 and then influenza of B/Victoria lineage, not contained in that season’s adult trivalent inactivated influenza vaccine (IIV). Overall adjusted end-of-season vaccine effectiveness (VE) was 52.4% (95% confidence interval (CI): 41.0–61.6) against influenza-confirmed primary care consultation, 54.5% (95% CI: 41.6–64.5) against influenza A(H1N1)pdm09 and 54.2% (95% CI: 33.1–68.6) against influenza B. In 2–17 year-olds, adjusted VE for LAIV was 57.6% (95% CI: 25.1 to 76.0) against any influenza, 81.4% (95% CI: 39.6–94.3) against influenza B and 41.5% (95% CI: −8.5 to 68.5) against influenza A(H1N1)pdm09. These estimates demonstrate moderate to good levels of protection, particularly against influenza B in children, but relatively less against influenza A(H1N1)pdm09. Despite lineage mismatch in the trivalent IIV, adults younger than 65 years were still protected against influenza B. These results provide reassurance for the UK to continue its influenza immunisation programme planned for 2016/17.

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 Baseline Levels of Influenza-Specific B Cells and T Cell Responses Modulate Human Immune Responses to Swine Variant Influenza A/H3N2 Vaccine

Vaccines ◽  
2020 ◽  
Vol 8 (1) ◽  
pp. 126
Author(s):  
Lilin Lai ◽  
Nadine Rouphael ◽  
Yongxian Xu ◽  
Amy C. Sherman ◽  
Srilatha Edupuganti ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
Influenza A ◽  
Vaccine Dose ◽  
T Cell Responses ◽  
Post Vaccination ◽  
Cell Responses ◽  
Cellular Immune Responses ◽  
Cellular Immune

The cellular immune responses elicited by an investigational vaccine against an emergent variant of influenza (H3N2v) are not fully understood. Twenty-five subjects, enrolled in an investigational influenza A/H3N2v vaccine study, who received two doses of vaccine 21 days apart, were included in a sub-study of cellular immune responses. H3N2v-specific plasmablasts were determined by ELISpot 8 days after each vaccine dose and H3N2v specific CD4+ T cells were quantified by intracellular cytokine and CD154 (CD40 ligand) staining before vaccination, 8 and 21 days after each vaccine dose. Results: 95% (19/20) and 96% (24/25) subjects had pre-existing H3N2v specific memory B, and T cell responses, respectively. Plasmablast responses at Day 8 after the first vaccine administration were detected against contemporary H3N2 strains and correlated with hemagglutination inhibition HAI (IgG: p = 0.018; IgA: p < 0.001) and Neut (IgG: p = 0.038; IgA: p = 0.021) titers and with memory B cell frequency at baseline (IgA: r = 0.76, p < 0.001; IgG: r = 0.74, p = 0.0001). The CD4+ T cells at Days 8 and 21 expanded after prime vaccination and this expansion correlated strongly with early post-vaccination HAI and Neut titers (p ≤ 0.002). In an adult population, the rapid serological response observed after initial H3N2v vaccination correlates with post-vaccination plasmablasts and CD4+ T cell responses.

Safety and immune responses following administration of H1N1 live attenuated influenza vaccine in Thais

Vaccine ◽  
2013 ◽  
Vol 31 (11) ◽  
pp. 1503-1509 ◽  
Author(s):  
Benjaluck Phonrat ◽  
Punnee Pitisuttithum ◽  
Supat Chamnanchanunt ◽  
Pilaipan Puthavathana ◽  
Nathamon Ngaosuwankul ◽  
...  
Keyword(s):  
Immune Responses ◽  
Influenza Vaccine ◽  
Live Attenuated Influenza Vaccine

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 Influenza A (N1-N9) and Influenza B (B/Vic and B/Yam) Neuraminidase Pseudotypes as Tools for Pandemic Preparedness and Improved Influenza Vaccine design

2021 ◽  
Author(s):  
Kelly A.S. da Costa ◽  
Joanne Marie M. Del Rosario ◽  
Matteo Ferrari ◽  
Sneha Vishwanath ◽  
Benedikt Asbach ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Influenza Vaccine ◽  
Influenza A ◽  
Vaccine Design ◽  
Influenza B ◽  
Pandemic Preparedness ◽  
Post Vaccination ◽  
Vaccine Immunogenicity ◽  
Viral Pseudotypes

AbstractTo better understand how inhibition of the influenza neuraminidase (NA) protein contributes to protection against influenza, and to investigate its breadth and cross-neutralizing activity, we have produced lentiviral vectors pseudotyped with an avian H11 hemagglutinin (HA) and the NA (N1-N9) of all influenza A and (B/Victoria and B/Yamagata) influenza B subtypes. These NA viral pseudotypes (PV) possess stable NA activity and can be utilized as target antigens in in vitro assays to assess vaccine immunogenicity. Employing these NA PV, we have developed an enzyme-linked lectin assay (pELLA) for routine serology to measure neuraminidase inhibition (NI) titers of reference antisera, monoclonal antibodies, and post-vaccination sera with various influenza antigens. We have also shown that pELLA is more sensitive than the commercially available NA-Fluor™ in detecting NA inhibition in these samples. Our studies may lead to establishing the protective NA titer that contributes to NA-based immunity. This will aid in the design of superior, longer lasting, and more broadly protective vaccines that can be employed together with HA-targeted vaccines in a pre-pandemic approach.

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