RhCMV serostatus and vaccine adjuvant impact immunogenicity of RhCMV/SIV vaccines

W. L.William Chang, Jesse D. Deere, Hung T. Kieu, Luis D. Castillo, Kawthar Machmach, Xiaoying Shen, Georgia D. Tomaras, Barbara Shacklett, Peter A. Barry, Dennis J. Hartigan-O’Connor, Ellen Elizabeth Sparger

Research output: Contribution to journalArticle

Abstract

Rhesus cytomegalovirus (RhCMV) strain 68-1-vectored simian immunodeficiency virus (RhCMV/SIV) vaccines are associated with complete clearance of pathogenic SIV challenge virus, non-canonical major histocompatibility complex restriction, and absent antibody responses in recipients previously infected with wild-type RhCMV. This report presents the first investigation of RhCMV/SIV vaccines in RhCMV-seronegative macaques lacking anti-vector immunity. Fifty percent of rhesus macaques (RM) vaccinated with a combined RhCMV-Gag, -Env, and -Retanef (RTN) vaccine controlled pathogenic SIV challenge despite high peak viremia. However, kinetics of viral load control by vaccinated RM were considerably delayed compared to previous reports. Impact of a TLR5 agonist (flagellin; FliC) on vaccine efficacy and immunogenicity was also examined. An altered vaccine regimen containing an SIV Gag-FliC fusion antigen instead of Gag was significantly less immunogenic and resulted in reduced protection. Notably, RhCMV-Gag and RhCMV-Env vaccines elicited anti-Gag and anti-Env antibodies in RhCMV-seronegative RM, an unexpected contrast to vaccination of RhCMV-seropositive RM. These findings confirm that RhCMV-vectored SIV vaccines significantly protect against SIV pathogenesis. However, pre-existing vector immunity and a pro-inflammatory vaccine adjuvant may influence RhCMV/SIV vaccine immunogenicity and efficacy. Future investigation of the impact of pre-existing anti-vector immune responses on protective immunity conferred by this vaccine platform is warranted.

Original languageEnglish (US)
Article number14056
JournalScientific reports
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2020

ASJC Scopus subject areas

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    Chang, W. L. W., Deere, J. D., Kieu, H. T., Castillo, L. D., Machmach, K., Shen, X., Tomaras, G. D., Shacklett, B., Barry, P. A., Hartigan-O’Connor, D. J., & Sparger, E. E. (2020). RhCMV serostatus and vaccine adjuvant impact immunogenicity of RhCMV/SIV vaccines. Scientific reports, 10(1), [14056]. https://doi.org/10.1038/s41598-020-71075-x