Designing multivalent immunogens for alphavirus vaccine optimization.
Alphavirus
/ immunology
Alphavirus Infections
/ immunology
Amino Acids
/ chemistry
Animals
Antibodies, Neutralizing
/ blood
Antibodies, Viral
/ blood
Encephalitis Virus, Eastern Equine
/ immunology
Encephalitis Virus, Venezuelan Equine
/ immunology
Encephalomyelitis, Eastern Equine
/ immunology
Encephalomyelitis, Venezuelan Equine
/ immunology
Female
Immunogenicity, Vaccine
Mice
Vaccine Development
Vaccines, Attenuated
/ immunology
Vaccines, Synthetic
/ immunology
Viral Envelope Proteins
/ chemistry
Viral Vaccines
/ immunology
Alphaviruses
Computational and structural vaccine design
Eastern equine encephalitis virus
Murine model
Physicochemical property (PCP) consensus
Venezuelan equine encephalitis virus
Journal
Virology
ISSN: 1096-0341
Titre abrégé: Virology
Pays: United States
ID NLM: 0110674
Informations de publication
Date de publication:
09 2021
09 2021
Historique:
received:
13
07
2020
revised:
15
10
2020
accepted:
22
11
2020
pubmed:
8
4
2021
medline:
24
12
2021
entrez:
7
4
2021
Statut:
ppublish
Résumé
There is a pressing need for vaccines against mosquito-borne alphaviruses such as Venezualen and eastern equine encephalitis viruses (VEEV, EEEV). We demonstrate an approach to vaccine development based on physicochemical properties (PCP) of amino acids to design a PCP-consensus sequence of the epitope-rich B domain of the VEEV major antigenic E2 protein. The consensus "spike" domain was incorporated into a live-attenuated VEEV vaccine candidate (ZPC/IRESv1). Mice inoculated with either ZPC/IRESv1 or the same virus containing the consensus E2 protein fragment (VEEVconE2) were protected against lethal challenge with VEEV strains ZPC-738 and 3908, and Mucambo virus (MUCV, related to VEEV), and had comparable neutralizing antibody titers against each virus. Both vaccines induced partial protection against Madariaga virus (MADV), a close relative of EEEV, lowering mortality from 60% to 20%. Thus PCP-consensus sequences can be integrated into a replicating virus that could, with further optimization, provide a broad-spectrum vaccine against encephalitic alphaviruses.
Identifiants
pubmed: 33823988
pii: S0042-6822(20)30236-1
doi: 10.1016/j.virol.2020.11.010
pmc: PMC8277671
mid: NIHMS1684848
pii:
doi:
Substances chimiques
Amino Acids
0
Antibodies, Neutralizing
0
Antibodies, Viral
0
Vaccines, Attenuated
0
Vaccines, Synthetic
0
Viral Envelope Proteins
0
Viral Vaccines
0
glycoprotein E2, equine encephalitis virus
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
117-124Subventions
Organisme : NIAID NIH HHS
ID : R01 AI137332
Pays : United States
Organisme : NIAID NIH HHS
ID : R24 AI120942
Pays : United States
Informations de copyright
Copyright © 2021 Elsevier Inc. All rights reserved.
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