AUTHOR=Lassaunière Ria , Tiemessen Caroline T. 

TITLE=FcγR Genetic Variation and HIV-1 Vaccine Efficacy: Context And Considerations

JOURNAL=Frontiers in Immunology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.788203

DOI=10.3389/fimmu.2021.788203

ISSN=1664-3224

ABSTRACT=<p>Receptors for the crystallisable fragment (Fc) of immunoglobulin (Ig) G, Fcγ receptors (FcγRs), link the humoral and cellular arms of the immune response, providing a diverse armamentarium of antimicrobial effector functions. Findings from HIV-1 vaccine efficacy trials highlight the need for further study of Fc-FcR interactions in understanding what may constitute vaccine-induced protective immunity. These include host genetic correlates identified within the low affinity Fcγ-receptor locus in three HIV-1 efficacy trials – VAX004, RV144, and HVTN 505. This perspective summarizes our present knowledge of FcγR genetics in the context of findings from HIV-1 efficacy trials, and draws on genetic variation described in other contexts, such as mother-to-child HIV-1 transmission and HIV-1 disease progression, to explore the potential contribution of <italic>FcγR</italic> variability in modulating different HIV-1 vaccine efficacy outcomes. Appreciating the complexity and the importance of the collective contribution of variation within the <italic>FCGR</italic> gene locus is important for understanding the role of FcγRs in protection against HIV-1 acquisition.</p>