Rhesus macaque cytomegalovirus deploys viral Fcγ receptors to evade antibody-mediated cellular immunity

Abstract Cytomegalovirus (CMV) is a top priority in vaccine development due to the high burden of disease immunocompromised populations and congenitally infected infants. Evidence suggests that CMV-specific Fc-mediated antibody effector responses, such as dependent cellular phagocytosis cytotoxicity, are key for prevention multiple CMV outcomes. However, human expresses three Fcγ receptors have been shown vitro synergistically interfere with anti-CMV IgG engagement host (FcγRs). We recently identified functionally homologous viral (vFcγRs) rhesus macaque (RM) (RhCMV), which allow us validate function vFcγRs vivo. Using full-length (FL) RhCMV backbone (Taher, et al. 2020), we produced mutant lacking all (ΔvFcγR) compared infection CMV-seronegative male RMs ΔvFcγR (n=4) FL (n=3). experienced similar peak DNAemia levels 1 week post but was contained by 3 while remained detectable plasma through 9. The observed early control concurrent RhCMV-specific responses 3–4 weeks both groups. kinetics binding neutralizing were between two groups RMs, suggesting anti-RhCMV may more effective against deleted vFcγRs. Thus, promising candidates immunogens improve Fc mediated efficacy reduce incidence CMV-associated birth defects transplant complications. Supported grants from NIH P01-AI129859 P01-AI129859_S1, T32-CA009111, National Foundation ECRA