The Negative Effect of Preexisting Immunity on Influenza Vaccine Responses Transcends the Impact of Vaccine Formulation Type and Vaccination History

Moritzky, Savannah A; Richards, Katherine A.; Glover, Maryah A; Krammer, Florian; Chaves, Francisco A.; Topham, David J.; Branche, Angela; Nayak, Jennifer L.; Sant, Andrea J.

doi:10.1093/infdis/jiac068

Cited by 11 publications

(13 citation statements)

References 48 publications

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“…Annually repeated influenza vaccination attenuates the antibody response to inactivated influenza vaccines [16,[27][28][29][30][31][32][33]. Consistently, we found that individuals previously vaccinated exhibited a reduced fold-increase in HI titers and lower SCR postvaccination, compared with those without prior vaccination in the past 3 years.…”

Section: Discussionsupporting

confidence: 82%

“…Additionally, the levels of influenza-specific CD4 T cell activation and pre-existing antibodies are correlated with a robust early vaccine-induced antibody response and strongly correlated with vaccination history [14]. Although vaccine-induced influenzaspecific CD4 T cell responses have positive correlations with serological responses, repeated annual influenza vaccination may impair CD4 T cells, causing defects in eliciting antibody responses [15,16].…”

Section: Introductionmentioning

confidence: 99%

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Association of vaccine‐specific regulatory T cells with reduced antibody response to repeated influenza vaccination

Lin,

Hsiao,

Pan

et al. 2023

Eur J Immunol

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Repeated annual influenza vaccinations have been associated with reduced vaccine‐induced antibody responses. This prospective study aimed to explore the role of vaccine antigen‐ specific regulatory T (Treg) cells in antibody response to repeated annual influenza vaccination. We analyzed pre‐ and post‐vaccination hemagglutination inhibition (HI) titers, seroconversion rates, seroprotection rates, vaccine antigen hemagglutinin (HA) ‐specific Treg cells, and conventional T (Tconv) cells. We compared these parameters between vaccinees with or without vaccine‐induced seroconversion. Our multivariate logistic regression revealed that prior vaccination was significantly associated with a decreased likelihood of achieving seroconversion for both H1N1(adjusted odds ratio [OR], 0.03; 95% confidence interval [CI], 0.01‐0.13) and H3N2 (adjusted OR, 0.09; 95% CI, 0.03‐0.30). Furthermore, individuals who received repeated vaccinations had significantly higher levels of pre‐existing HA‐specific Treg cells than those who did not. We also found that vaccine‐induced fold‐increases in HI titers and seroconversion were negatively correlated with pre‐existing HA‐specific Treg cells and positively correlated with the ratio of Tconv to Treg cells. Overall, our findings suggest that repeated annual influenza vaccination is associated with a lower vaccine‐induced antibody response and a higher frequency of vaccine‐specific Treg cells. However, a lower frequency of pre‐existing Treg cells correlates with a higher post‐vaccination antibody response.This article is protected by copyright. All rights reserved

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Section: Discussionsupporting

confidence: 82%

Section: Introductionmentioning

confidence: 99%

Association of vaccine‐specific regulatory T cells with reduced antibody response to repeated influenza vaccination

Lin,

Hsiao,

Pan

et al. 2023

Eur J Immunol

View full text Add to dashboard Cite

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“…The magnitude of IgG‐titer increases in HRs was inversely correlated with pre‐existing titers, reflecting the “antibody ceiling effect” previously reported for HI and IgG responses during infection 24,25 and vaccination 13,16,26,27 . High titers of pre‐existing antibodies could lead to more rapid antigen clearance, 28,29 leading to limited activation of pre‐existing CD4+ T cells and memory B cells 24 . However, a ceiling effect for IgG responses was not detrimental since HRs, in which it was more evident, were still capable of mounting robust HI‐antibody responses.…”

Section: Discussionmentioning

confidence: 57%

“…Our findings suggest that host inflammatory status and pre‐existing influenza immunity can impact influenza vaccine responses through different mechanisms. The older poor vaccine responders may be immunologically restricted in their ability to generate vaccine‐specific HI‐responses, but pre‐existing influenza‐specific B cells can still be activated to produce IgG antibodies, 14,24 although this boosting appears to have a threshold. The magnitude of IgG‐titer increases in HRs was inversely correlated with pre‐existing titers, reflecting the “antibody ceiling effect” previously reported for HI and IgG responses during infection 24,25 and vaccination 13,16,26,27 .…”

Section: Discussionmentioning

confidence: 99%

The impact of pre‐existing influenza antibodies and inflammatory status on the influenza vaccine responses in older adults

Kang

Lin

Jiang

et al. 2023

Influenza Resp Viruses

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Age‐associated immune changes and pre‐existing influenza immunity are hypothesized to reduce influenza vaccine effectiveness in older adults, although the contribution of each factor is unknown. Here, we constructed influenza‐specific IgG landscapes and determined baseline concentrations of cytokines typically associated with chronic inflammation in older adults (TNF‐α, IL‐10, IL‐6, and IFN‐γ) in 30 high and 29 low influenza vaccine responders (HR and LR, respectively). In a background of high H3 antibody titers, vaccine‐specific H3, but not H1, antibody titers were boosted in LRs to titers comparable to HRs. Pre‐vaccination concentrations of IL‐10 were higher in LRs compared with HRs and inversely correlated with titers of pre‐existing influenza antibodies. Baseline TNF‐α concentrations were positively correlated with fold‐increases in antibody titers in HRs. Our findings indicate that baseline inflammatory status is an important determinant for generating post‐vaccination hemagglutinin‐inhibition antibodies in older adults, and IgG responses can be boosted in the context of high pre‐existing immunity.

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“…The IFN-g ELISpot and intracellular cytokine staining (ICS) assays are frequently used to examine cellular immune responses elicited by influenza infection or vaccination (16)(17)(18)(19)(20)(21). A better insight into the magnitude, quality and durability of cellmediated immune responses can improve our understanding of the immunological mechanisms underlying viral clearance or vaccine effectiveness and may contribute to the identification of new correlates of protection.…”

Section: Discussionmentioning

confidence: 99%

Harmonization and qualification of an IFN-γ Enzyme-Linked ImmunoSpot assay (ELISPOT) to measure influenza-specific cell-mediated immunity within the FLUCOP consortium

et al. 2022

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Influenza continues to be the most important cause of viral respiratory disease, despite the availability of vaccines. Today’s evaluation of influenza vaccines mainly focuses on the quantitative and functional analyses of antibodies to the surface proteins haemagglutinin (HA) and neuraminidase (NA). However, there is an increasing interest in measuring cellular immune responses targeting not only mutation-prone surface HA and NA but also conserved internal proteins as these are less explored yet potential correlates of protection. To date, laboratories that monitor cellular immune responses use a variety of in-house procedures. This generates diverging results, complicates interlaboratory comparisons, and hampers influenza vaccine evaluation. The European FLUCOP project aims to develop and standardize assays for the assessment of influenza vaccine correlates of protection. This report describes the harmonization and qualification of the influenza-specific interferon-gamma (IFN-γ) Enzyme-Linked ImmunoSpot (ELISpot) assay. Initially, two pilot studies were conducted to identify sources of variability during sample analysis and spot enumeration in order to develop a harmonized Standard Operating Procedure (SOP). Subsequently, an assay qualification study was performed to investigate the linearity, intermediate precision (reproducibility), repeatability, specificity, Lower and Upper Limits of Quantification (LLOQ-ULOQ), Limit of Detection (LOD) and the stability of signal over time. We were able to demonstrate that the FLUCOP harmonized IFN-γ ELISpot assay procedure can accurately enumerate IFN-γ secreting cells in the analytical range of 34.4 Spot Forming Units (SFU) per million cells up to the technical limit of the used reader and in the linear range from 120 000 to 360 000 cells per well, in plates stored up to 6 weeks after development. This IFN-γ ELISpot procedure will hopefully become a useful and reliable tool to investigate influenza-specific cellular immune responses induced by natural infection or vaccination and can be an additional instrument in the search for novel correlates of protection.

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The Negative Effect of Preexisting Immunity on Influenza Vaccine Responses Transcends the Impact of Vaccine Formulation Type and Vaccination History

Cited by 11 publications

References 48 publications

Association of vaccine‐specific regulatory T cells with reduced antibody response to repeated influenza vaccination

Association of vaccine‐specific regulatory T cells with reduced antibody response to repeated influenza vaccination

The impact of pre‐existing influenza antibodies and inflammatory status on the influenza vaccine responses in older adults

Harmonization and qualification of an IFN-γ Enzyme-Linked ImmunoSpot assay (ELISPOT) to measure influenza-specific cell-mediated immunity within the FLUCOP consortium

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