HIV neutralizing antibodies: clinical correlates and implications for vaccines.

Neutralizing humoral immunity has been the subject of intense investigation since early human immunodeficiency virus (HIV) research. Although virtually all HIV-positive patients have antibodies capable of binding to HIV envelope protein, only a subset of these antibodies, termed neutralizing antibodies, are able to block viral entry into target cells. Neutralizing antibodies develop later than other immune responses, у12 weeks after infection [1, 2], and initially target only the infecting strain. Over time, in many patients this response broadens to allow recognition of heterologous strains [3, 4]. It is generally thought that neutralizing antibodies will be a critical component of a successful vaccine-elicited immune response. Given the immense diversity of HIV strains worldwide, vaccine-elicited neutralizing antibodies would ideally be broadly cross-reactive. To date, the anti-bodies elicited by candidate vaccines have had no or weak neutralizing activity, mainly against laboratory-adapted strains and with very limited breadth [5–7]. However , many HIV-infected individuals produce neutralizing antibodies, and a small fraction produce extremely potent neutralizing antibodies with activity against diverse clinical (primary) isolates [3, 4, 8– 11]. Understanding how broad neutralizing antibodies develop naturally in some HIV-1–infected patients should provide guidance for vaccine design. The prevalence of broadly reactive neutralizing an-tibodies in serum and the associated clinical parameters have been the subject of several recent studies [10, 12–14]. Euler and colleagues, in an article appearing in this issue of Journal [15], examined these findings in a European cohort. Euler et al [15] evaluated samples from 82 patients participating in the Amster-dam Cohort Studies. Because this cohort has been followed from seroconversion onward, the authors were able to look for associations between neutralizing antibod-ies and clinical outcomes, as well as im-munological parameters. They chose samples from 3 years after infection, allowing time for broad neutralizing antibodies to have developed. Neutralizing activity in serum was measured using the well-accepted TZM-bl assay and pseudo-viruses derived from primary isolates [2, 16]. They found that neutralizing antibody breadth varies widely among chronically infected patients. Consistent with findings in studies of other cohorts in multiple geographic areas [10–14], the authors observed that 33% of their patients with chronic HIV infection had broad neutralizing antibodies. An important finding was the lack of association between breadth of neutralizing antibodies and the time from seroconversion to diagnosis with AIDS, AIDS-related death, or the survival time after AIDS diagnosis. This agrees with findings in a Kenyan cohort [13]. The authors also noted a positive …