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

doi:10.1016/j.virol.2020.11.010

Designing multivalent immunogens for alphavirus vaccine optimization

Virology. 2021 Sep:561:117-124. doi: 10.1016/j.virol.2020.11.010. Epub 2021 Feb 5.

Authors

C M Read¹, Kenneth Plante², Grace Rafael¹, Shannan L Rossi³, Werner Braun⁴, Scott C Weaver⁵, Catherine H Schein⁶

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: chschein@utmb.edu.

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.

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

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Alphavirus / immunology*
Alphavirus Infections / immunology
Alphavirus Infections / prevention & control*
Amino Acids / chemistry
Animals
Antibodies, Neutralizing / blood
Antibodies, Neutralizing / immunology
Antibodies, Viral / blood
Antibodies, Viral / immunology
Encephalitis Virus, Eastern Equine / immunology
Encephalitis Virus, Venezuelan Equine / immunology*
Encephalomyelitis, Eastern Equine / immunology
Encephalomyelitis, Eastern Equine / prevention & control
Encephalomyelitis, Venezuelan Equine / immunology
Encephalomyelitis, Venezuelan Equine / prevention & control*
Female
Immunogenicity, Vaccine
Mice
Vaccine Development*
Vaccines, Attenuated / immunology
Vaccines, Synthetic / immunology
Viral Envelope Proteins / chemistry
Viral Envelope Proteins / genetics
Viral Envelope Proteins / immunology*
Viral Vaccines / immunology*

Substances

Amino Acids
Antibodies, Neutralizing
Antibodies, Viral
Vaccines, Attenuated
Vaccines, Synthetic
Viral Envelope Proteins
Viral Vaccines
glycoprotein E2, equine encephalitis virus

Abstract

Publication types

MeSH terms

Substances

Grants and funding