Extrapolating theoretical efficacy of inactivated influenza A/H5N1 virus vaccine from human immunogenicity studies.
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.
Department of Epidemiology, School of Public Health, University of Washington School, Seattle, WA, United States; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States.
Leora R
LR
Feldstein
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States; Center for Inference and Dynamics of Infectious Diseases, Fred Hutchinson Cancer Research Center, Seattle, WA, United States.
Laura
L
Matrajt
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States; Center for Inference and Dynamics of Infectious Diseases, Fred Hutchinson Cancer Research Center, Seattle, WA, United States; Department of Biostatistics, School of Public Health, University of Washington, Seattle, WA, United States.
M
M
Elizabeth Halloran
Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, United States; Department of Medicine, Baylor College of Medicine, Houston, TX, United States.
Wendy A
WA
Keitel
Center for Inference and Dynamics of Infectious Diseases, Fred Hutchinson Cancer Research Center, Seattle, WA, United States; Department of Biostatistics, College of Public Health and Health Professions and College of Medicine, University of Florida, Gainesville, FL, United States. Electronic address: ilongini@ufl.edu.
Ira M
IM
Longini
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000914:Antibodies, Viral / Q000097:blood; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D004306:Dose-Response Relationship, Immunologic; D004338:Drug Combinations; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D000071497:Immunogenicity, Vaccine; D053124:Influenza A Virus, H5N1 Subtype; D007252:Influenza Vaccines / Q000276:immunology* / Q000627:therapeutic use; D007251:Influenza, Human / Q000517:prevention & control*; D011136:Polysorbates / Q000008:administration & dosage; D016032:Randomized Controlled Trials as Topic; D013185:Squalene / Q000008:administration & dosage; D015164:Vaccines, Inactivated / Q000276:immunology / Q000627:therapeutic use; D024502:alpha-Tocopherol / Q000008:administration & dosage
D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D004338:Drug Combinations; D007252:Influenza Vaccines; C089950:MF59 oil emulsion; D011136:Polysorbates; D015164:Vaccines, Inactivated; D013185:Squalene; C550253:AS03 adjuvant; D024502:alpha-Tocopherol
Avian influenza; Influenza; Pandemic influenza; Vaccine efficacy; Vaccines