TY - JOUR
T1 - Designing multivalent immunogens for alphavirus vaccine optimization
AU - Read, C. M.
AU - Plante, Kenneth
AU - Rafael, Grace
AU - Rossi, Shannan L.
AU - Braun, Werner
AU - Weaver, Scott C.
AU - Schein, Catherine H.
N1 - Funding Information:
We thank the many others who assisted in these studies and/or supplied materials, especially Mathilda Guerbois Galla, Surendra Negi, Rafael Campos, Jianying Liu, Divya Mirchandani, Jessica Plante, Brandon James Trent, Karly Jade Catto and members of the World Reference Center for Emerging Viruses and Arboviruses and the Animal Resource Center. This work was funded by NIH grants R01 AI137332–02 and R24 AI120942 .
Publisher Copyright:
© 2021 Elsevier Inc.
PY - 2021/9
Y1 - 2021/9
N2 - 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.
AB - 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.
KW - Alphaviruses
KW - Computational and structural vaccine design
KW - Eastern equine encephalitis virus
KW - Murine model
KW - Physicochemical property (PCP) consensus
KW - Venezuelan equine encephalitis virus
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U2 - 10.1016/j.virol.2020.11.010
DO - 10.1016/j.virol.2020.11.010
M3 - Article
C2 - 33823988
AN - SCOPUS:85103706163
SN - 0042-6822
VL - 561
SP - 117
EP - 124
JO - Virology
JF - Virology
ER -