Adjuvants and the vaccine response to the DS-Cav1-stabilized fusion glycoprotein of respiratory syncytial virus

Sastry, Mallika; Zhang, Baoshan; Chen, Man; Joyce, M. Gordon; Kong, Wing-Pui; Chuang, Gwo-Yu; Ko, Kiyoon; Kumar, Azad; Silacci, Chiara; Thom, Michelle; Salazar, Andres M.; Corti, Davide; Lanzavecchia, Antonio; Taylor, Geraldine; Mascola, John R.; Graham, Barney S.; Kwong, Peter D.

doi:10.1371/journal.pone.0186854

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Adjuvants and the vaccine response to the DS-Cav1-stabilized fusion glycoprotein of respiratory syncytial virus

Sastry, Mallika Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America
Zhang, Baoshan Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America
Chen, Man Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America
Joyce, M. Gordon Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America
Kong, Wing-Pui Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America
Chuang, Gwo-Yu Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America
Ko, Kiyoon Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America
Kumar, Azad Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America
Silacci, Chiara Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Thom, Michelle The Pirbright Institute, Ash Road, Pirbright, Woking, Surrey GU24 0NF, United Kingdom
Salazar, Andres M. Oncovir Inc., Washington, D.C, United States of America
Corti, Davide Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland - Humabs BioMed SA, Bellinzona, Switzerland
Lanzavecchia, Antonio Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Taylor, Geraldine The Pirbright Institute, Ash Road, Pirbright, Woking, Surrey GU24 0NF, United Kingdom
Mascola, John R. Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America
Graham, Barney S. Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America
Kwong, Peter D. Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America

26.10.2017

Published in:

Plos one. - 2017, vol. 12, no. 10, p. e0186854

English Appropriate adjuvant selection may be essential to optimize the potency and to tailor the immune response of subunit vaccines. To induce protective responses against respiratory syncytial virus (RSV)—a highly prevalent childhood pathogen without a licensed vaccine—we previously engineered a pre-fusion-stabilized trimeric RSV F (pre-F) “DS-Cav1” immunogen, which induced high titer RSV-neutralizing antibodies, in mice and non-human primates, when formulated with adjuvants Poly (I:C) and Poly (IC:LC), respectively. To assess the impact of different adjuvants, here we formulated RSV F DS-Cav1 with multiple adjuvants and assessed immune responses. Very high RSV-neutralizing antibody responses (19,006 EC50) were observed in naïve mice immunized with 2 doses of DS-Cav1 adjuvanted with Sigma adjuvant system (SAS), an oil-in-water adjuvant, plus Carbopol; high responses (3658–7108) were observed with DS-Cav1 adjuvanted with Alum, SAS alone, Adjuplex, Poly (I:C) and Poly (IC:LC); and moderate responses (1251–2129) were observed with DS-Cav1 adjuvanted with the TLR4 agonist MPLA, Alum plus MPLA or AddaVax. In contrast, DS-Cav1 without adjuvant induced low-level responses (6). A balanced IgG1 and IgG2a (Th2/Th1) immune response was elicited in most of the high to very high response groups (all but Alum and Adjuplex). We also tested the immune response induced by DS-Cav1 in elderly mice with pre-existing DS-Cav1 immunity; we observed that DS-Cav1 adjuvanted with SAS plus Carbopol boosted the response 2-3-fold, whereas DS-Cav1 adjuvanted with alum boosted the response 5-fold. Finally, we tested whether a mixture of ISA 71 VG and Carbopol would enhanced the antibody response in DS-Cav1 immunized calves. While pre-F-stabilized bovine RSV F induced very high titers in mice when adjuvanted with SAS plus Carbopol, the addition of Carbopol to ISA 71 VG did not enhance immune responses in calves. The vaccine response to pre-F-stabilized RSV F is augmented by adjuvant, but the degree of adjuvant-induced enhancement appears to be both context-dependent and species-specific.

Language

English

Classification

Medicine

License

CC BY

Open access status

gold

Identifiers

RERO DOC 327192
DOI 10.1371/journal.pone.0186854
ARK ark:/12658/srd1319065

Persistent URL

https://n2t.net/ark:/12658/srd1319065

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