AUTHOR=Scholte F. E. M. , Karaaslan E. , O’Neal T. J. , Sorvillo T. E. , Genzer S. C. , Welch S. R. , Coleman-McCray J. D. , Spengler J. R. , Kainulainen M. H. , Montgomery J. M. , Pegan S. D. , Bergeron E. , Spiropoulou C. F. 

TITLE=Vaccination with the Crimean-Congo hemorrhagic fever virus viral replicon vaccine induces NP-based T-cell activation and antibodies possessing Fc-mediated effector functions

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=13

YEAR=2023

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2023.1233148

DOI=10.3389/fcimb.2023.1233148

ISSN=2235-2988

ABSTRACT=<p>Crimean-Congo hemorrhagic fever virus (CCHFV; family <italic>Nairoviridae</italic>) is a tick-borne pathogen that frequently causes lethal disease in humans. CCHFV has a wide geographic distribution, and cases have been reported in Africa, Asia, the Middle East, and Europe. Availability of a safe and efficacious vaccine is critical for restricting outbreaks and preventing disease in endemic countries. We previously developed a virus-like replicon particle (VRP) vaccine that provides complete protection against homologous and heterologous lethal CCHFV challenge in mice after a single dose. However, the immune responses induced by this vaccine are not well characterized, and correlates of protection remain unknown. Here we comprehensively characterized the kinetics of cell-mediated and humoral immune responses in VRP-vaccinated mice, and demonstrate that they predominantly target the nucleoprotein (NP). NP antibodies are not associated with protection through neutralizing activity, but VRP vaccination results in NP antibodies possessing Fc-mediated antibody effector functions, such as complement activation (ADCD) and antibody-mediated cellular phagocytosis (ADCP). This suggests that Fc-mediated effector functions may contribute to this vaccine’s efficacy.</p>