Designing multivalent immunogens for alphavirus vaccine optimization.

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.

• Authors: C M Read, Kenneth Plante, Grace Rafael, Shannan L Rossi, Werner Braun, Scott C Weaver, Catherine H Schein
• Journal: Virology (Virology) Vol. 561 Pg. 117-124 (09 2021) ISSN: 1096-0341 [Electronic] United States
• PMID: 33823988 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2021 Elsevier Inc. All rights reserved.

Chemical References

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

Topics

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