Designing multivalent immunogens for alphavirus vaccine optimization

C. M. Read, Kenneth Plante, Grace Rafael, Shannan L. Rossi, Werner Braun, Scott C. Weaver, Catherine H. Schein

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
JournalVirology
DOIs
StateAccepted/In press - 2021

Keywords

  • Alphaviruses
  • Computational and structural vaccine design
  • Eastern equine encephalitis virus
  • Murine model
  • Physicochemical property (PCP) consensus
  • Venezuelan equine encephalitis virus

ASJC Scopus subject areas

  • Virology

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