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Designing multivalent immunogens for alphavirus vaccine optimization.

C M Read1, Kenneth Plante2, Grace Rafael1

  • 1Department of Microbiology and Immunology, University of Texas Medical Branch at Galveston, 301 University Boulevard, Galveston, TX, 77555, USA.

Virology
|April 7, 2021
PubMed
Summary
This summary is machine-generated.

Developing a novel vaccine strategy using physicochemical properties (PCP) of amino acids shows promise for combating mosquito-borne alphaviruses like Venezuelan equine encephalitis virus (VEEV) and eastern equine encephalitis virus (EEEV). This approach offers potential for broad-spectrum protection against these dangerous encephalitic viruses.

Keywords:
AlphavirusesComputational and structural vaccine designEastern equine encephalitis virusMurine modelPhysicochemical property (PCP) consensusVenezuelan equine encephalitis virus

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Area of Science:

  • Virology
  • Immunology
  • Vaccine Development

Background:

  • Mosquito-borne alphaviruses, including Venezuelan equine encephalitis virus (VEEV) and eastern equine encephalitis virus (EEEV), pose significant public health threats.
  • There is an urgent requirement for effective vaccines against these encephalitic viruses.

Purpose of the Study:

  • To explore a novel vaccine development strategy based on physicochemical properties (PCP) of amino acids.
  • To design and test a VEEV vaccine candidate incorporating a PCP-consensus sequence of the E2 protein's epitope-rich B domain.

Main Methods:

  • A PCP-consensus sequence was designed for the VEEV E2 protein's B domain.
  • This consensus sequence was incorporated into a live-attenuated VEEV vaccine candidate (ZPC/IRESv1) and a variant (VEEVconE2).
  • Mice were vaccinated and subsequently challenged with lethal strains of VEEV, Mucambo virus (MUCV), and Madariaga virus (MADV).

Main Results:

  • Both vaccine candidates conferred protection against lethal VEEV and MUCV challenge in mice.
  • Vaccinated mice exhibited comparable neutralizing antibody titers against VEEV, MUCV, and related alphaviruses.
  • Partial protection was observed against Madariaga virus (MADV), reducing mortality from 60% to 20%.

Conclusions:

  • Physicochemical property-consensus sequences can be integrated into live-attenuated viruses for vaccine development.
  • This strategy holds potential for creating broad-spectrum vaccines against encephalitic alphaviruses.
  • Further optimization may lead to enhanced efficacy and wider protection against related viruses.