Extrapolating theoretical efficacy of inactivated influenza A/H5N1 virus vaccine from human immunogenicity studies

Leora R Feldstein; Laura Matrajt; M Elizabeth Halloran; Wendy A Keitel; Ira M Longini; H5N1 Vaccine Working Group

doi:10.1016/j.vaccine.2016.05.067

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Extrapolating theoretical efficacy of inactivated influenza A/H5N1 virus vaccine from human immunogenicity studies

Journal article

Open access

Peer reviewed

Extrapolating theoretical efficacy of inactivated influenza A/H5N1 virus vaccine from human immunogenicity studies

Leora R Feldstein, Laura Matrajt, M Elizabeth Halloran, Wendy A Keitel, Ira M Longini and H5N1 Vaccine Working Group

Vaccine, Vol.34(33), pp.3796-3802

07/19/2016

DOI: 10.1016/j.vaccine.2016.05.067

PMCID: PMC5168719

PMID: 27268778

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Abstract

•Adjuvanted vaccines provided the highest vaccine efficacy after 1 and 2 doses.•Vaccine efficacy of adjuvanted vaccines was 17% higher than unadjuvanted vaccines.•Proportion of overall maximum efficacy obtained after 1 dose of vaccine was computed.•This proportion ranged from 0.32 to 0.57 in adjuvanted vaccines. Influenza A virus subtype H5N1 has been a public health concern for almost 20years due to its potential ability to become transmissible among humans. Phase I and II clinical trials have assessed safety, reactogenicity and immunogenicity of inactivated influenza A/H5N1 virus vaccines. A shortage of vaccine is likely to occur during the first months of a pandemic. Hence, determining whether to give one dose to more people or two doses to fewer people to best protect the population is essential. We use hemagglutination–inhibition antibody titers as an immune correlate for avian influenza vaccines. Using an established relationship to obtain a theoretical vaccine efficacy from immunogenicity data from thirteen arms of six phase I and phase II clinical trials of inactivated influenza A/H5N1 virus vaccines, we assessed: (1) the proportion of theoretical vaccine efficacy achieved after a single dose (defined as primary response level), and (2) whether theoretical efficacy increases after a second dose, with and without adjuvant. Participants receiving vaccine with AS03 adjuvant had higher primary response levels (range: 0.48–0.57) compared to participants receiving vaccine with MF59 adjuvant (range: 0.32–0.47), with no observed trends in primary response levels by antigen dosage. After the first and second doses, vaccine with AS03 at dosage levels 3.75, 7.5 and 15mcg had the highest estimated theoretical vaccine efficacy: Dose (1) 45% (95% CI: 36–57%), 53% (95% CI: 42–63%) and 55% (95% CI: 44–64%), respectively and Dose (2) 93% (95% CI: 89–96%), 97% (95% CI: 95–98%) and 97% (95% CI: 96–100%), respectively. On average, the estimated theoretical vaccine efficacy of lower dose adjuvanted vaccines (AS03 and MF59) was 17% higher than that of higher dose unadjuvanted vaccines, suggesting that including an adjuvant is dose-sparing. These data indicate adjuvanted inactivated influenza A/H5N1 virus vaccine produces high theoretical efficacy after two doses to protect individuals against a potential avian influenza pandemic.

Influenza

Vaccines

Avian influenza

Pandemic influenza

Vaccine efficacy

Details

Title: Subtitle: Extrapolating theoretical efficacy of inactivated influenza A/H5N1 virus vaccine from human immunogenicity studies
Creators: Leora R Feldstein - Department of Epidemiology, School of Public Health, University of Washington School, Seattle, WA, United States
Laura Matrajt - Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States
M Elizabeth Halloran - Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States
Wendy A Keitel - Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, United States
Ira M Longini - Center for Inference and Dynamics of Infectious Diseases, Fred Hutchinson Cancer Research Center, Seattle, WA, United States
H5N1 Vaccine Working Group
Contributors: P L Winokur (Contributor) - University of Iowa, Internal Medicine
Resource Type: Journal article
Publication Details: Vaccine, Vol.34(33), pp.3796-3802
DOI: 10.1016/j.vaccine.2016.05.067
PMID: 27268778
PMCID: PMC5168719
NLM abbreviation: Vaccine
ISSN: 0264-410X
eISSN: 1873-2518
Publisher: Elsevier Ltd
Grant note: DOI: 10.13039/100004319, name: Pfizer; DOI: 10.13039/100004336, name: Novartis; DOI: 10.13039/100000057, name: National Institute of General Medical Sciences, award: U01-GM070749, U54-GM111274-01; DOI: 10.13039/100000060, name: National Institute of Allergy and Infectious Diseases, award: R37-AI032042
Language: English
Date published: 07/19/2016
Academic Unit: Infectious Diseases; Medicine Administration; Internal Medicine
Record Identifier: 9984094343402771

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