Qualitative and Quantitative Variables that Affect the Potency of Fc-Mediated Effector Function In Vitro and In Vivo: Considerations for Passive Immunization Using Non-Neutralizing Antibodies

Passive immunization studies in non-human primates have established unequivocally that virus neutralization can prevent infection, providing the impetus for current intense efforts to identify immunogens that elicit broadly neutralizing antibodies in humans. Although Fc-mediated effector function may also contribute to protection by neutralizing antibodies, its role in protection by non-neutralizing antibodies is controversial. Here, I review the literature suggesting a role for Fc-mediated effector by non-neutralizing antibodies in protective immunity against HIV-1 with a primary focus on antibody mediated cellular cytotoxicity (ADCC) and related responses such as antibody-dependent cellular viral inhibition (ADCVI). Special emphasis is placed on qualitative and quantitative variables including antibody specificity and dose-response behavior in vitro and in vivo, which I propose as key variables in future passive immunization studies. Properly configured, these studies should clarify the role of Fc-mediated effector function by nonneutralizing antibodies in protection against HIV-1.