Fc Functions and Anti-HIV Neutralizing Antibodies: A Perspective

Controversy exists around the relative merits of Fc functions in controlling or preventing HIV-1 infection. Proponents point to general correlations of Fc functions with control of HIV, indicating that non-neutralizing antibodies could force immune escape, as observed in the early experiments with Fc mutants of the b12-neutralizing monoclonal antibody. Nay-sayers point to the primary role of neutralization in the control of HIV, the general failure of vaccine trials including antibodies with Fc functions, and the lack of additional benefit with newer broadly neutralizing monoclonal antibodies, such as PGT121. The truth may lie somewhere in between and there are lessons to be learned from the utility of Fc functions in other viral infections. In general, however, the additional benefit of Fc function over and above robust anti-HIV neutralizing antibodies may be modest. The intense primary research focus on delivering and inducing potent and broadly neutralizing antibodies, regardless of their Fc function potential, is justified.