Safety, Reactogenicity, and Immunogenicity of Inactivated Monovalent Influenza A(H5N1) Virus Vaccine Administered With or Without AS03 Adjuvant.
BACKGROUND
The national stockpile for influenza pandemic preparedness includes vaccines against an array of strains and adjuvants that could be utilized to induce immunologic priming as a pandemic wave emerges. We assessed the feasibility of a strategy that allows the flexibility of postmanufacture mixture of vaccine and adjuvant at the point of care.


METHODS
We conducted a randomized, double-blind, multicenter trial among healthy adults aged 18-49 years who received 2 doses of inactivated influenza A/Indonesia/05/2005 (H5N1 clade 2.2.3) virus vaccine containing either 3.75, 7.5, or 15 µg of hemagglutinin (HA) with or without AS03 adjuvant, administered 21 days apart. Subjects were observed for local (injection site) and systemic reactogenicity and adverse events. Sera were tested for hemagglutination inhibition (HAI) and microneutralization (MN) antibody levels against the homologous strain and 4 heterologous avian strains.


RESULTS
Vaccine containing ASO3 adjuvant was associated with significantly more local reactions compared with nonadjuvanted vaccine, but these were short-lived and resolved spontaneously. Although the immune response to nonadjuvanted vaccine was poor, 2 doses of AS03-adjuvanted vaccine containing as little as 3.75 µg of HA elicited robust immune responses resulting in seroprotective titers (≥1:40) to the homologous strain in ≥86% of subjects by HAI and in 95% of subjects by MN. Cross-clade antibody responses were also observed with AS03-adjuvanted vaccine, but not nonadjuvanted vaccine.


CONCLUSIONS
AS03 adjuvant formulated with inactivated vaccine at the administration site significantly enhanced the immune responses to H5N1 vaccine and has the potential to markedly improve vaccine responses and accelerate delivery during an influenza pandemic.


BACKGROUND
NCT01317758.
Center for Vaccine Development , University of Maryland School of Medicine , Baltimore.
Wilbur H
WH
Chen
Group Health Research Institute , Seattle, Washington.
Lisa A
LA
Jackson
Vanderbilt Vaccine Research Program , Vanderbilt University School of Medicine , Nashville, Tennessee.
Kathryn M
KM
Edwards
Baylor College of Medicine , Houston, Texas.
Wendy A
WA
Keitel
EMMES Corporation , Rockville, Maryland.
Heather
H
Hill
Southern Research , Birmingham, Alabama.
Diana L
DL
Noah
Vanderbilt Vaccine Research Program , Vanderbilt University School of Medicine , Nashville, Tennessee.
C Buddy
CB
Creech
Baylor College of Medicine , Houston, Texas.
Shital M
SM
Patel
EMMES Corporation , Rockville, Maryland.
Brian
B
Mangal
Center for Vaccine Development , University of Maryland School of Medicine , Baltimore.
Karen L
KL
Kotloff
adjuvants; avian influenza; pandemic influenza vaccine