Vaccines with MF59 Adjuvant Expand the Antibody Repertoire to Target Protective Sites of Pandemic Avian H5N1 Influenza Virus

被引：229

作者：

Khurana, Surender ^{[1
]}

Chearwae, Wanida ^{[1
]}

Castellino, Flora ^{[2
]}

Manischewitz, Jody ^{[1
]}

King, Lisa R. ^{[1
]}

Honorkiewicz, Agnieszka ^{[1
]}

Rock, Michael T. ^{[3
]}

Edwards, Kathryn M. ^{[3
]}

Del Giudice, Giuseppe ^{[2
]}

Rappuoli, Rino ^{[2
]}

Golding, Hana ^{[1
]}

机构：

[1] US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD 20892 USA

[2] Novartis Vaccines & Diagnost Res Ctr, I-53100 Siena, Italy

[3] Vanderbilt Univ, Med Ctr, Div Pediat Infect Dis, Nashville, TN 37232 USA

来源：

SCIENCE TRANSLATIONAL MEDICINE | 2010年 / 2卷 / 15期

关键词：

A VIRUSES; IMMUNOGENICITY; HEMAGGLUTININ; SAFETY; BINDING; MEMORY; ADULTS;

D O I：

10.1126/scitranslmed.3000624

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页数：7

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