Non Progressors: a possible protective effect against disease progression Long lasting CCR5 internalization by antibodies in a subset of Long Term

Abstract Rationale: Exposure to HIV-1 does not necessarily result in infection and progression toward disease. Thus suggests that the control of viral infection may be achieved. Antibodies to CCR5 have been detected in HIV-exposed but uninfected subjects (ESN), thus they could be involved in HIV protection. Objectives: To assess whether anti-CCR5 antibodies may also contribute to slow HIV-disease progression, we searched for anti-CCR5 antibodies in 497 subjects, including 85 Long Term Non Progressors (LTNP), 70 Progressors, 135 HIV+ HAART treated, and 207 seronegative donors. Findings: We found anti-CCR5 antibodies in a fraction of LTNP (23.5%), but not in the other populations studied (p<0.0001). These antibodies recognized a conformational epitope within the first extramembrane loop of CCR5 and they induced a stable and long lasting down regulation of CCR5 on surface of T lymphocytes, which inhibited HIV entry. In addition, CD4+ lymphocytes from LTNP having anti CCR5 antibodies are resistance to R5 strains of HIV-1. Follow-up studies showed that the loss of anti-CCR5 antibodies occurred in some subjects and this loss was significantly associated with a progression toward disease, whereas subjects who retained anti CCR5 Abs maintained their LTNP status. Conclusions: Induction of anti-CCR5 Abs could be relevant to vaccine design and therapeutics. From bloodjournal.hematologylibrary.org by guest on June 3, 2013. For personal use only.