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Vaccines with MF59 adjuvant expand the antibody repertoire to target protective sites of pandemic avian H5N1 influenza virus.Sci Transl Med. 2010 Jan 20; 2(15):15ra5.ST
Abstract
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.
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MeSH
Adjuvants, ImmunologicAdsorptionAnimalsAntibodies, MonoclonalAntibodies, NeutralizingAntibodies, ViralAntibody FormationBirdsDisease OutbreaksEpitopesHumansHydrogen-Ion ConcentrationInfluenza A Virus, H5N1 SubtypeInfluenza VaccinesInfluenza in BirdsInfluenza, HumanKineticsModels, MolecularPeptide LibraryPolysorbatesProtein FoldingProtein Structure, TertiarySqualeneVaccination
Pub Type(s)
Journal Article
Research Support, N.I.H., Extramural
Language
eng
PubMed ID
20371470
Citation
Khurana, Surender, et al. "Vaccines With MF59 Adjuvant Expand the Antibody Repertoire to Target Protective Sites of Pandemic Avian H5N1 Influenza Virus." Science Translational Medicine, vol. 2, no. 15, 2010, pp. 15ra5.
Khurana S, Chearwae W, Castellino F, et al. Vaccines with MF59 adjuvant expand the antibody repertoire to target protective sites of pandemic avian H5N1 influenza virus. Sci Transl Med. 2010;2(15):15ra5.
Khurana, S., Chearwae, W., Castellino, F., Manischewitz, J., King, L. R., Honorkiewicz, A., Rock, M. T., Edwards, K. M., Del Giudice, G., Rappuoli, R., & Golding, H. (2010). Vaccines with MF59 adjuvant expand the antibody repertoire to target protective sites of pandemic avian H5N1 influenza virus. Science Translational Medicine, 2(15), 15ra5. https://doi.org/10.1126/scitranslmed.3000624
Khurana S, et al. Vaccines With MF59 Adjuvant Expand the Antibody Repertoire to Target Protective Sites of Pandemic Avian H5N1 Influenza Virus. Sci Transl Med. 2010 Jan 20;2(15):15ra5. PubMed PMID: 20371470.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR
T1 - Vaccines with MF59 adjuvant expand the antibody repertoire to target protective sites of pandemic avian H5N1 influenza virus.
AU - Khurana,Surender,
AU - Chearwae,Wanida,
AU - Castellino,Flora,
AU - Manischewitz,Jody,
AU - King,Lisa R,
AU - Honorkiewicz,Agnieszka,
AU - Rock,Michael T,
AU - Edwards,Kathryn M,
AU - Del Giudice,Giuseppe,
AU - Rappuoli,Rino,
AU - Golding,Hana,
PY - 2010/4/8/entrez
PY - 2010/4/8/pubmed
PY - 2010/6/29/medline
SP - 15ra5
EP - 15ra5
JF - Science translational medicine
JO - Sci Transl Med
VL - 2
IS - 15
N2 - 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.
SN - 1946-6242
UR - https://www.unboundmedicine.com/medline/citation/20371470/Vaccines_with_MF59_adjuvant_expand_the_antibody_repertoire_to_target_protective_sites_of_pandemic_avian_H5N1_influenza_virus_
L2 - https://stm.sciencemag.org/cgi/pmidlookup?view=short&pmid=20371470
DB - PRIME
DP - Unbound Medicine
ER -
