Vaccines with MF59 adjuvant expand the antibody repertoire to target protective sites of pandemic avian H5N1 influenza virus

• Published in: Science translational medicine Vol. 2; no. 15; p. 15ra5
• Main Authors: Khurana, Surender, Chearwae, Wanida, Castellino, Flora, Manischewitz, Jody, King, Lisa R, Honorkiewicz, Agnieszka, Rock, Michael T, Edwards, Kathryn M, Del Giudice, Giuseppe, Rappuoli, Rino, Golding, Hana
• Format: Journal Article
• Language: English
• Published: United States 20.01.2010
• Subjects: Adjuvants, Immunologic - administration & dosage; Adjuvants, Immunologic - pharmacology; Adsorption - drug effects; Animals; Antibodies, Monoclonal - immunology; Antibodies, Neutralizing - immunology; Antibodies, Viral - immunology; Antibody Formation - drug effects; Birds - immunology; Birds - virology; Disease Outbreaks - prevention & control; Epitopes - chemistry; Epitopes - immunology; Humans; Hydrogen-Ion Concentration - drug effects; Influenza A Virus, H5N1 Subtype - drug effects; Influenza A Virus, H5N1 Subtype - immunology; Influenza in Birds - epidemiology; Influenza in Birds - immunology; Influenza in Birds - prevention & control; Influenza in Birds - virology; Influenza Vaccines - immunology; Influenza, Human - epidemiology; Influenza, Human - immunology; Influenza, Human - prevention & control; Influenza, Human - virology; Kinetics; Models, Molecular; Peptide Library; Polysorbates - pharmacology; Protein Folding - drug effects; Protein Structure, Tertiary; Squalene - immunology; Squalene - pharmacology; Vaccination
• DOI: 10.1126/scitranslmed.3000624

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.