1992;256:1687C1690. induced with a prime-boost regimen in chimpanzees. The data suggest that in chimpanzees, the presence of neutralizing Abs correlates with protection for animals challenged intravenously with a high dose of a homologous strain of HIV-1, and they demonstrate for the first time the induction of neutralizing Abs to homologous and heterologous primary isolates. Most viral vaccines induce immunity which limits virus replication, prevents disease, and facilitates clearance of the contamination. Few, if any, induce sterilizing immunity, defined as the ability to completely prevent virus contamination (19). Protection is usually achieved by stimulating the humoral and cellular arms of the immune response, both of which are needed to eliminate free virus and infected cells. It has been ML224 postulated that to prevent and contain human immunodeficiency virus type 1 (HIV-1) contamination, stimulation of cellular immunity is more critical than induction of antibodies (Abs) because contamination is thought to occur as the result of contact with infected cells as well as with free virions. Support for this concept comes from the findings that many uncovered but uninfected subjects display cellular responses in the absence of Abs (reviewed in reference 37) and Tnf that vaccine-induced immunity to certain other retroviral infections, such as feline leukemia virus, does not correlate with the presence of neutralizing Abs (NAbs) (12). Moreover, in the absence of sterilizing immunity, cellular immunity is believed to be necessary if eradication of contamination is to be achieved. The need for Abs to protect against HIV-1 and other viruses is also well documented. Most efficacious viral vaccines ML224 in current clinical use induce NAbs, which play a crucial role in prophylaxis (33). Abs are essential for the elimination of free virus particles and thus for reduction of the magnitude of the infectious inoculum. Furthermore, effective levels of functional Abs also help to contain virus spread as virions are produced by infected cells. Indeed, an important role for Abs has been documented in studies of HIV-1 contamination with humans and chimpanzees in which Abs have been shown, directly or by association, to be involved in preventing, delaying, and decreasing the extent of HIV-1 contamination (8, 9, 15, 31, 36, 38). Chimpanzees ML224 represent a particularly valuable model for the study of HIV-1 prophylaxis because they are the only nonhuman primates that can be readily infected with HIV-1 and because they can be immunized and challenged with HIV-1 under controlled conditions. Numerous studies have been conducted with either passive or active immunization and challenge with free or cell-associated virus. In most of these studies, protection has been correlated with the presence of NAbs (3, 9C11, 15) and, when sterilizing immunity was not achieved, the presence of NAbs was frequently associated with delayed onset or reduced parameters of contamination (9, 15, 38). Like sera from human recipients of various candidate HIV-1 vaccines, sera from immunized chimpanzees have been shown to display significant levels of ML224 NAbs for the immunizing HIV-1 strains, but the detection of NAbs to primary isolates has been difficult to achieve (4, 16, 38). This failure to demonstrate primary isolate NAbs could be due to the inability of ML224 a particular vaccine to induce such Abs, to an antigenic mismatch.