Designing multivalent immunogens for alphavirus vaccine optimization.
Virology
; 561: 117-124, 2021 09.
Article
en En
| MEDLINE
| ID: mdl-33823988
ABSTRACT
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Vacunas Virales
/
Proteínas del Envoltorio Viral
/
Infecciones por Alphavirus
/
Alphavirus
/
Virus de la Encefalitis Equina Venezolana
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Encefalomielitis Equina Venezolana
/
Desarrollo de Vacunas
Límite:
Animals
Idioma:
En
Revista:
Virology
Año:
2021
Tipo del documento:
Article
País de afiliación:
Estados Unidos