Non-replicating adenovirus based Mayaro virus vaccine elicits protective immune responses and cross protects against other alphaviruses.
Adenoviridae
/ genetics
Alphavirus
/ immunology
Animals
Antibodies, Neutralizing
/ immunology
Antibodies, Viral
/ immunology
Chikungunya Fever
/ prevention & control
Chikungunya virus
/ immunology
Cross Protection
/ immunology
Disease Models, Animal
Female
Genetic Engineering
/ methods
Genetic Vectors
/ genetics
Immunization
Male
Mice
Mice, Inbred C57BL
Viral Vaccines
/ administration & dosage
Journal
PLoS neglected tropical diseases
ISSN: 1935-2735
Titre abrégé: PLoS Negl Trop Dis
Pays: United States
ID NLM: 101291488
Informations de publication
Date de publication:
04 2021
04 2021
Historique:
received:
20
10
2020
accepted:
15
03
2021
revised:
16
04
2021
pubmed:
2
4
2021
medline:
30
7
2021
entrez:
1
4
2021
Statut:
epublish
Résumé
Mayaro virus (MAYV) is an alphavirus endemic to South and Central America associated with sporadic outbreaks in humans. MAYV infection causes severe joint and muscle pain that can persist for weeks to months. Currently, there are no approved vaccines or therapeutics to prevent MAYV infection or treat the debilitating musculoskeletal inflammatory disease. In the current study, a prophylactic MAYV vaccine expressing the complete viral structural polyprotein was developed based on a non-replicating human adenovirus V (AdV) platform. Vaccination with AdV-MAYV elicited potent neutralizing antibodies that protected WT mice against MAYV challenge by preventing viremia, reducing viral dissemination to tissues and mitigating viral disease. The vaccine also prevented viral-mediated demise in IFN⍺R1-/- mice. Passive transfer of immune serum from vaccinated animals similarly prevented infection and disease in WT mice as well as virus-induced demise of IFN⍺R1-/- mice, indicating that antiviral antibodies are protective. Immunization with AdV-MAYV also generated cross-neutralizing antibodies against two related arthritogenic alphaviruses-chikungunya and Una viruses. These cross-neutralizing antibodies were protective against lethal infection in IFN⍺R1-/- mice following challenge with these heterotypic alphaviruses. These results indicate AdV-MAYV elicits protective immune responses with substantial cross-reactivity and protective efficacy against other arthritogenic alphaviruses. Our findings also highlight the potential for development of a multi-virus targeting vaccine against alphaviruses with endemic and epidemic potential in the Americas.
Identifiants
pubmed: 33793555
doi: 10.1371/journal.pntd.0009308
pii: PNTD-D-20-01861
pmc: PMC8051823
doi:
Substances chimiques
Antibodies, Neutralizing
0
Antibodies, Viral
0
Viral Vaccines
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0009308Subventions
Organisme : NIAID NIH HHS
ID : R41 AI138964
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI109680
Pays : United States
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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