Vaccine efficacy and immune interference: co-administering COVID-19 and influenza vaccines

ABSTRACT Influenza is a global public health problem. Current seasonal influenza vaccines have highly variable efficacy, and thus attempts to develop broadly protective universal influenza vaccines with durable protection are under way. While much attention is given to the virus-related factors contributing to inconsistent vaccine responses, host-associated factors are often neglected. Growing evidences suggest that host factors including age, biological sex, pregnancy, and immune history play important roles as modifiers of influenza virus vaccine efficacy. We hypothesize that host genetics, the hormonal milieu, and gut microbiota contribute to host-related differences in influenza virus vaccine efficacy. This review highlights the current insights and future perspectives into host-specific factors that impact influenza vaccine-induced immunity and protection. Consideration of the host factors that affect influenza vaccine-induced immunity might improve influenza vaccines by providing empirical evidence for optimizing or even personalizing vaccine type, dose, and use of adjuvants for current seasonal and future universal influenza vaccines.

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Relative vaccine efficacy of high-dose versus standard-dose influenza vaccines in preventing probable influenza in a Medicare Fee-for-Service population

Vaccine ◽

10.1016/j.vaccine.2020.05.020 ◽

2020 ◽

Vol 38 (29) ◽

pp. 4548-4556 ◽

Cited By ~ 1

Author(s):

Misti Paudel ◽

Salah Mahmud ◽

Ami Buikema ◽

Stephanie Korrer ◽

Damon Van Voorhis ◽

...

Keyword(s):

Vaccine Efficacy ◽

Standard Dose ◽

Influenza Vaccines ◽

High Dose ◽

Fee For Service

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Distinguishing Causation from Correlation in the Use of Correlates of Protection to Evaluate and Develop Influenza Vaccines

American Journal of Epidemiology ◽

10.1093/aje/kwz227 ◽

2019 ◽

Vol 189 (3) ◽

pp. 185-192 ◽

Cited By ~ 1

Author(s):

Wey Wen Lim ◽

Nancy H L Leung ◽

Sheena G Sullivan ◽

Eric J Tchetgen Tchetgen ◽

Benjamin J Cowling

Keyword(s):

Vaccine Efficacy ◽

Vaccine Development ◽

Influenza Vaccines ◽

Protective Effects ◽

Immune Markers ◽

Immune Marker ◽

Correlates Of Protection ◽

Rational Vaccine Design ◽

Individual Protection ◽

Protection Against Infection

Abstract There is increasing attention to the need to identify new immune markers for the evaluation of existing and new influenza vaccines. Immune markers that could predict individual protection against infection and disease, commonly called correlates of protection (CoPs), play an important role in vaccine development and licensing. Here, we discuss the epidemiologic considerations when evaluating immune markers as potential CoPs for influenza vaccines and emphasize the distinction between correlation and causation. While an immune marker that correlates well with protection from infection can be used as a predictor of vaccine efficacy, it should be distinguished from an immune marker that plays a mechanistic role in conferring protection against a clinical endpoint—the latter might be a more reliable predictor of vaccine efficacy and a more appropriate target for rational vaccine design. To clearly distinguish mechanistic and nonmechanistic CoPs, we suggest using the term “correlates of protection” for nonmechanistic CoPs, and ‘‘mediators of protection’’ for mechanistic CoPs. Furthermore, because the interactions among and relative importance of correlates or mediators of protection can vary according to age or prior vaccine experience, the effect sizes and thresholds for protective effects for CoPs could also vary in different segments of the population.

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A new approach to estimate vaccine efficacy based on immunogenicity data applied to influenza vaccines administered by the intradermal or intramuscular routes

Human Vaccines ◽

10.4161/hv.6.10.12636 ◽

2010 ◽

Vol 6 (10) ◽

pp. 841-848 ◽

Cited By ~ 17

Author(s):

Laurent Coudeville ◽

Philippe Andre ◽

Fabrice Bailleux ◽

Françoise Weber ◽

Stanley Plotkin

Keyword(s):

Vaccine Efficacy ◽

Influenza Vaccines ◽

New Approach

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Strategies Targeting Hemagglutinin as a Universal Influenza Vaccine

Vaccines ◽

10.3390/vaccines9030257 ◽

2021 ◽

Vol 9 (3) ◽

pp. 257

Author(s):

Brianna L. Bullard ◽

Eric A. Weaver

Keyword(s):

Influenza Virus ◽

Influenza Vaccine ◽

Vaccine Efficacy ◽

Influenza Season ◽

Surface Protein ◽

Antigenic Drift ◽

Influenza Vaccines ◽

Viral Diversity ◽

Universal Influenza Vaccine ◽

Ha Protein

Influenza virus has significant viral diversity, both through antigenic drift and shift, which makes development of a vaccine challenging. Current influenza vaccines are updated yearly to include strains predicted to circulate in the upcoming influenza season, however this can lead to a mismatch which reduces vaccine efficacy. Several strategies targeting the most abundant and immunogenic surface protein of influenza, the hemagglutinin (HA) protein, have been explored. These strategies include stalk-directed, consensus-based, and computationally derived HA immunogens. In this review, we explore vaccine strategies which utilize novel antigen design of the HA protein to improve cross-reactive immunity for development of a universal influenza vaccine.

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Relative Vaccine Efficacy of High-Dose Versus Standard-Dose Influenza Vaccines in Preventing Probable Influenza in a Medicare Fee-for-Service Population

SSRN Electronic Journal ◽

10.2139/ssrn.3487817 ◽

2019 ◽

Author(s):

Misti Paudel ◽

Salah Mahmud ◽

Ami Buikema ◽

Stephanie Korrer ◽

Damon Van Voorhis ◽

...

Keyword(s):

Vaccine Efficacy ◽

Standard Dose ◽

Influenza Vaccines ◽

High Dose ◽

Fee For Service

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Protective Efficacy of Recombinant Influenza Hemagglutinin Ectodomain Fusions

Viruses ◽

10.3390/v13091710 ◽

2021 ◽

Vol 13 (9) ◽

pp. 1710

Author(s):

Nidhi Mittal ◽

Nayanika Sengupta ◽

Sameer Kumar Malladi ◽

Poorvi Reddy ◽

Madhuraj Bhat ◽

...

Keyword(s):

Vaccine Efficacy ◽

Influenza A ◽

Protective Efficacy ◽

Neutralizing Antibody ◽

Surface Proteins ◽

Influenza Vaccines ◽

High Yield ◽

Suspension Cells ◽

Water Emulsion ◽

Antibody Titers

In current seasonal influenza vaccines, neutralizing antibody titers directed against the hemagglutinin surface protein are the primary correlate of protection. These vaccines are, therefore, quantitated in terms of their hemagglutinin content. Adding other influenza surface proteins, such as neuraminidase and M2e, to current quadrivalent influenza vaccines would likely enhance vaccine efficacy. However, this would come with increased manufacturing complexity and cost. To address this issue, as a proof of principle, we have designed genetic fusions of hemagglutinin ectodomains from H3 and H1 influenza A subtypes. These recombinant H1-H3 hemagglutinin ectodomain fusions could be transiently expressed at high yield in mammalian cell culture using Expi293F suspension cells. Fusions were trimeric, and as stable in solution as their individual trimeric counterparts. Furthermore, the H1-H3 fusion constructs were antigenically intact based on their reactivity with a set of conformation-specific monoclonal antibodies. H1-H3 hemagglutinin ectodomain fusion immunogens, when formulated with the MF59 equivalent adjuvant squalene-in-water emulsion (SWE), induced H1 and H3-specific humoral immune responses equivalent to those induced with an equimolar mixture of individually expressed H1 and H3 ectodomains. Mice immunized with these ectodomain fusions were protected against challenge with heterologous H1N1 (Bel/09) and H3N2 (X-31) mouse-adapted viruses with higher neutralizing antibody titers against the H1N1 virus. Use of such ectodomain-fused immunogens would reduce the number of components in a vaccine formulation and allow for the inclusion of other protective antigens to increase influenza vaccine efficacy.

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Safety, Immunogenicity, and Efficacy of a COVID-19 Vaccine (NVX-CoV2373) Co-administered With Seasonal Influenza Vaccines

10.1101/2021.06.09.21258556 ◽

2021 ◽

Author(s):

Paul Heath ◽

Seth Toback ◽

Eva Galiza ◽

Catherine Cosgrove ◽

James Galloway ◽

...

Keyword(s):

Influenza Vaccine ◽

Vaccine Efficacy ◽

Seasonal Influenza ◽

Haemagglutination Inhibition ◽

Influenza Vaccines ◽

Main Study ◽

Electronic Diary ◽

Open Label ◽

Age Appropriate ◽

Study Participants

Background The safety and immunogenicity profile of COVID-19 vaccines when administered concomitantly with seasonal influenza vaccines has not yet been reported. Methods A sub-study on influenza vaccine co-administration was conducted as part of the phase 3 randomized trial of the safety and efficacy of NVX-CoV2373. The first ~400 participants meeting main study entry criteria and with no contraindications to influenza vaccination were invited to join the sub-study. After randomization in a 1:1 ratio to receive NVX-CoV2373 (n=217) or placebo (n=214), sub-study participants received an age-appropriate, licensed, open-label influenza vaccine with dose 1 of NVX-CoV2373. Reactogenicity was evaluated via electronic diary for 7 days post-vaccination in addition to monitoring for unsolicited adverse events (AEs), medically-attended AEs (MAAEs), and serious AEs (SAEs). Influenza haemagglutination inhibition and SARS-CoV-2 anti-spike IgG assays were performed. Vaccine efficacy against PCR-confirmed, symptomatic COVID-19 was assessed. Comparisons were made between sub-study and main study participants. Findings Sub-study participants were younger, more racially diverse, and had fewer comorbid conditions than main study participants. Reactogenicity events more common in the co-administration group included tenderness (70.1% vs 57.6%) or pain (39.7% vs 29.3%) at injection site, fatigue (27.7% vs 19.4%), and muscle pain (28.3% vs 21.4%). Rates of unsolicited AEs, MAAEs, and SAEs were low and balanced between the two groups. Co-administration resulted in no change to influenza vaccine immune response, while a reduction in antibody responses to the NVX-CoV2373 vaccine was noted. Vaccine efficacy in the sub-study was 87.5% (95% CI: -0.2, 98.4) while efficacy in the main study was 89.8% (95% CI: 79.7, 95.5). Interpretation This is the first study to demonstrate the safety, immunogenicity, and efficacy profile of a COVID-19 vaccine when co-administered with seasonal influenza vaccines. The results suggest concomitant vaccination may be a viable immunisation strategy. Funding This study was funded by Novavax, Inc.

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