Vaccines with MF59 adjuvant expand the antibody repertoire to target protective sites of pandemic avian H5N1 influenza virus.
Vaccines against influenza viruses with pandemic potential, including H5N1, are under development. Because of a lack of preexisting immunity to these viruses, adjuvants (immune potentiators or enhancers) are needed to improve immune responses, to conserve scarce vaccine, and for cross-protection against strains that have drifted evolutionarily from the original. Aluminum-based adjuvants do not improve vaccine immunogenicity for influenza subunit vaccines, whereas oil-in-water adjuvants are effective, especially with H5N1-inactivated vaccines. We used whole-genome-fragment phage display libraries followed by surface plasmon resonance (SPR) technologies to elucidate the effect of different adjuvants on the antibody repertoire against H5N1 vaccine in humans. The oil-in-water adjuvant MF59 induced epitope spreading from HA2 to HA1 in hemagglutinin (HA) and neuraminidase relative to unadjuvanted or aluminum-adjuvanted vaccines. Moreover, we observed an increase by a factor of 20 in the frequency of HA1-to-HA2-specific phage clones in sera after MF59-adjuvanted vaccine administration and a factor of 2 to 3 increase in the avidity of antibodies binding to properly folded HA1(28-319), as measured by SPR. The adjuvant-dependent increase in binding to conformational HA1 epitopes correlated with broadening of cross-clade neutralization and predicted improved in vivo protection. Thus, MF59 adjuvant improves the immune response to a H5N1 vaccine by inducing qualitative and quantitative expansion of the antibody repertoires with protective potential.
Khurana
Surender
S
Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA.
Chearwae
Wanida
W
Castellino
Flora
F
Manischewitz
Jody
J
King
Lisa R
LR
Honorkiewicz
Agnieszka
A
Rock
Michael T
MT
Edwards
Kathryn M
KM
Del Giudice
Giuseppe
G
Rappuoli
Rino
R
Golding
Hana
H
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology*; D000327:Adsorption / Q000187:drug effects; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology*; D000917:Antibody Formation / Q000187:drug effects; D001717:Birds / Q000276:immunology / Q000821:virology; D004196:Disease Outbreaks / Q000517:prevention & control*; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D006801:Humans; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D053124:Influenza A Virus, H5N1 Subtype / Q000187:drug effects / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D005585:Influenza in Birds / Q000453:epidemiology / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D007251:Influenza, Human / Q000453:epidemiology / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D007700:Kinetics; D008958:Models, Molecular; D019151:Peptide Library; D011136:Polysorbates / Q000494:pharmacology*; D017510:Protein Folding / Q000187:drug effects; D017434:Protein Structure, Tertiary; D013185:Squalene / Q000276:immunology / Q000494:pharmacology*; D014611:Vaccination
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000939:Epitopes; D007252:Influenza Vaccines; C089950:MF59 oil emulsion; D019151:Peptide Library; D011136:Polysorbates; D013185:Squalene