Background:  To determine the protective potential of the humoral immune response against HIV-1 in vivo we evaluated the potency of 3 neutralizing antibodies (2G12, 2F5, and 4E10) in suppressing viral rebound in 6 acutely and 8 chronically HIV-1-infected patients undergoing interruption ART.

Methods:  Starting 1 day before ART was stopped, patients received 13 passive immunizations with the 3 monoclonal antibodies over an 11-week period and were further followed until week 24 and closely monitored immunologically and virologically. Patients were selected according to the sensitivity of pre-treatment viral isolates to the 3 monoclonal antibodies.

Results:  Three chronically infected patients either totally suppressed viremia during the passive immunization or had a significantly delayed or lower rebound compared to previous treatment interruptions. Rebound in acutely infected individuals was compared to a control group of 12 patients with acute infection undergoing interruption of ART. Upon cessation of ART, antibody-treated, acutely infected individuals rebounded significantly later than patients of the control group (Kaplan–Meyer p = 0.0286; Fisher’s exact p = 0.0128). Four patients showed extended control at lower viral loads than before ART. Sequential viral isolates derived under antibody treatment showed no relevant changes in the sensitivity to monoclonal antibodies 2F5 and 4E10, nor were sequence changes in the epitopes of these antibodies apparent. In contrast, we observed a pronounced resistance of the rebounding virus to monoclonal antibody 2G12 in 11 of the 13 patients that carried initially 2G12-sensitive virus.  Moreover, ratios of plasma concentrations to in vitro inhibitory doses for 2G12 were much higher in responding than in non-responding patients (p = 0.0175) suggesting an  influence of 2G12 dosage and activity on the outcome of the trial.

Conclusions:  Of 14 patients, 7 responded to the antibody treatment with a clearly delayed or decreased rebound thus providing the first direct evidence that neutralizing antibodies can in principle contain viremia in human HIV-1 infection. By giving first insight on the potency, breadth, and titers of neutralizing antibodies required for in vivo activity, our data underline both the potential as also the limits of HIV-1 vaccines based on humoral immunity.

Keywords: neutralizing antibodies; passive immunization; vaccine