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Read CM, Plante K, Rafael G, et al. Designing multivalent immunogens for alphavirus vaccine optimization. Virology. 2021;561:117-124doi: 10.1016/j.virol.2020.11.010.
Read, C. M., Plante, K., Rafael, G., Rossi, S. L., Braun, W., Weaver, S. C., & Schein, C. H. (2021). Designing multivalent immunogens for alphavirus vaccine optimization. Virology, 561117-124. https://doi.org/10.1016/j.virol.2020.11.010
Read, C M, et al. "Designing multivalent immunogens for alphavirus vaccine optimization." Virology vol. 561 (2021): 117-124. doi: https://doi.org/10.1016/j.virol.2020.11.010
Read CM, Plante K, Rafael G, Rossi SL, Braun W, Weaver SC, Schein CH. Designing multivalent immunogens for alphavirus vaccine optimization. Virology. 2021 Sep;561:117-124. doi: 10.1016/j.virol.2020.11.010. Epub 2021 Feb 05. PMID: 33823988; PMCID: PMC8277671.
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Virology. 2021 Sep;561:117-124. doi: 10.1016/j.virol.2020.11.010. Epub 2021 Feb 05.

Designing multivalent immunogens for alphavirus vaccine optimization.

Virology

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

Affiliations

  1. Department of Microbiology and Immunology, University of Texas Medical Branch at Galveston, 301 University Boulevard, Galveston, TX, 77555, USA.
  2. Department of Microbiology and Immunology, University of Texas Medical Branch at Galveston, 301 University Boulevard, Galveston, TX, 77555, USA; Institute for Human Infections and Immunity (IHII), University of Texas Medical Branch at Galveston, 301 University Boulevard, Galveston, TX, 77555, USA; World Reference Center for Emerging Viruses and Arboviruses, University of Texas Medical Branch at Galveston, 301 University Boulevard, Galveston, TX, 77555, USA.
  3. Department of Microbiology and Immunology, University of Texas Medical Branch at Galveston, 301 University Boulevard, Galveston, TX, 77555, USA; Department of Pathology, University of Texas Medical Branch at Galveston, 301 University Boulevard, Galveston, TX, 77555, USA; Institute for Human Infections and Immunity (IHII), University of Texas Medical Branch at Galveston, 301 University Boulevard, Galveston, TX, 77555, USA.
  4. Department of Biochemistry and Molecular Biology, University of Texas Medical Branch at Galveston, 301 University Boulevard, Galveston, TX, 77555, USA; Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch at Galveston, 301 University Boulevard, Galveston, TX, 77555, USA.
  5. Department of Microbiology and Immunology, University of Texas Medical Branch at Galveston, 301 University Boulevard, Galveston, TX, 77555, USA; Institute for Human Infections and Immunity (IHII), University of Texas Medical Branch at Galveston, 301 University Boulevard, Galveston, TX, 77555, USA; World Reference Center for Emerging Viruses and Arboviruses, University of Texas Medical Branch at Galveston, 301 University Boulevard, Galveston, TX, 77555, USA; Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch at Galveston, 301 University Boulevard, Galveston, TX, 77555, USA.
  6. Department of Biochemistry and Molecular Biology, University of Texas Medical Branch at Galveston, 301 University Boulevard, Galveston, TX, 77555, USA; Institute for Human Infections and Immunity (IHII), University of Texas Medical Branch at Galveston, 301 University Boulevard, Galveston, TX, 77555, USA. Electronic address: [email protected].

PMID: 33823988 PMCID: PMC8277671 DOI: 10.1016/j.virol.2020.11.010

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.

Copyright © 2021 Elsevier Inc. All rights reserved.

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

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