The neutralizing mAb mixture prevented acquisition whereas the non-neutralizing mAb mixture did not. On the other hand, this mixture afforded post-infection control of viraemia, suggesting that Fc-mediated effector function contributes to this type of protection. Similar results were reported for another antibody specific for the immunodominant region of gp41 but no functional

Saracatinib order data other than virus capture was provided in that study.[16] Post-infection control is also a common finding for neutralizing mAbs used at doses insufficient to block acquisition (summarized in ref. [19]). Given that the in vivo half-lives of mAbs are short, typically ranging from 3 days to 2 weeks, they must exert their activities early after passive immunization as post-infection control by Fiebig Stage VI.[19] The short-term effect probably is to protect components of the immune system early in infection such that they can mature and mediate post-infection control after mAb decay. This possibility is supported by studies in mice showing that NK-mediated lysis of target cells expressing a foreign antigen early in the immune response results in strong CD4+ T Ibrutinib ic50 cell, CD8+ T cell and antibody responses downstream to release of the foreign antigen.[73] It is reasonable to expect that a similar

phenomenon would follow ADCC-induced lysis of target cells early in infection. This form of Fc-mediated protection would be most important in limiting the expansion of the local also founder population or perhaps decreasing systemic viral spread (Fig. 3). Correlations have been reported repeatedly between ADCC or ADCVI and post-infection control in vaccinated NHPs,[74-78] supporting this possibility. Despite the repeated correlations between Fc-mediated effector function and post-infection control in both active and passive immunization studies in NHPs, no study shows that passive immunization with a non-neutralizing mAb can block acquisition. Until a definitive passive immunization study employing a non-neutralizing antibody with Fc-mediated effector function, including an attenuated LALA variant as a negative

control, either rules this possibility in or out, the field is left with correlations. Two recent NHP vaccine studies report an inverse correlation between reduced acquisition and ADCC titres.[79, 80] In addition to the NHP studies, increasingly solid support indicating a role of Fc-mediated protection in preventing acquisition is developing from studies of infected and vaccinated humans. A recent study in HIV-infected mothers with high viral loads showed an inverse correlation between ADCC titres in breast milk and probability of transmission to their infants.[81] No such correlation was found for neutralization.[81] The earliest vaccine study reported an inverse correlation between ADCVI titres and risk of infection in a subgroup of vaccines in the VAX004 Phase III efficacy trial, although no overall protection was observed.