Adjuvant selection impacts the correlates of vaccine protection against Ebola infection.


Journal

Vaccine
ISSN: 1873-2518
Titre abrégé: Vaccine
Pays: Netherlands
ID NLM: 8406899

Informations de publication

Date de publication:
15 06 2020
Historique:
received: 10 10 2019
revised: 23 02 2020
accepted: 04 05 2020
pubmed: 19 5 2020
medline: 28 4 2021
entrez: 19 5 2020
Statut: ppublish

Résumé

The establishment of correlates of protection is particularly relevant in the context of rare, highly lethal pathogens such as filoviruses. We previously demonstrated that an Ebola glycoprotein virus-like particle (VLP) vaccine, when given as two intramuscular doses, conferred protection from challenge in a murine challenge model. In this study, we compared the ability of Advax inulin-based adjuvant formulations (Advax1-4) to enhance Ebola VLP vaccine protection in mice. After two immunizations, Advax-adjuvants that included a TLR9 agonist component induced high IgG responses, with complete protection against Ebola virus challenge. Although anti-Ebola IgG levels waned over time, protection was durable and was still evident 150 days post-immunization. Mice were protected after just a single VLP immunization with Advax-2 or -4 adjuvants. Advax-adjuvanted VLPs induced a stronger IFN-γ, TNF and IL-12 signature and serum transferred from Advax-adjuvanted vaccinees was able to transfer protection to naïve animals, showing that Ebola protection can be achieved by antibodies in the absence of cellular immunity. By contrast, serum from vaccinees incorporating a pICLC adjuvant did not transfer protection despite high IgG levels on ELISA. These data highlight the importance of adjuvant selection for development of a successful Ebola VLP vaccine.

Identifiants

pubmed: 32418798
pii: S0264-410X(20)30627-7
doi: 10.1016/j.vaccine.2020.05.009
pmc: PMC7272269
mid: NIHMS1591464
pii:
doi:

Substances chimiques

Adjuvants, Immunologic 0
Antibodies, Viral 0
Inulin 9005-80-5

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

4601-4608

Subventions

Organisme : NIAID NIH HHS
ID : HHSN272200800039C
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI061142
Pays : United States

Informations de copyright

Copyright © 2020 Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest NP is affiliated with Vaxine Pty Ltd, a company having a financial interest in Advax adjuvants. The other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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Auteurs

Sabrina M Stronsky (SM)

Molecular and Translational Sciences, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, United States.

Christopher L Cooper (CL)

Molecular and Translational Sciences, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, United States.

Jesse Steffens (J)

Molecular and Translational Sciences, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, United States.

Sean Van Tongeren (S)

Molecular and Translational Sciences, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, United States.

Sina Bavari (S)

Molecular and Translational Sciences, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, United States.

Karen A Martins (KA)

Molecular and Translational Sciences, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, United States.

Nikolai Petrovsky (N)

Vaxine Pty Ltd., Bedford Park, Adelaide 5042, Australia; Flinders University, Adelaide 5042, Australia. Electronic address: nikolai.petrovsky@flinders.edu.au.

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Classifications MeSH