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 - 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
UR - http://www.scopus.com/inward/record.url?scp=85103706163&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85103706163&partnerID=8YFLogxK
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 -