Monoclonal CCR5 Antibody: A Promising Therapy for HIV.

HIV is one of the world's most devastating viral infections and has claimed tens of millions of lives worldwide since it was first identified in the 1980s. There is no cure for HIV infection. However, with tremendous progress in HIV diagnosis, prevention, and treatment, HIV has become a manageable chronic health disease. CCR5 is an important coreceptor used by HIV to infect target cells, and genetic deficiency of the chemokine receptor CCR5 confers a significant degree of protection against HIV infection. In addition, since CCR5 deficiency does not appear to cause any adverse health effects, targeting this coreceptor is a promising strategy for the treatment and prevention of HIV. Monoclonal antibodies are frequently used as therapeutics for many diseases and therefore are being used as a potential therapy for HIV-1 infection. This review reports on CCR5 antibody research in detail and describes the role and advantages of CCR5 antibodies in HIV prevention or treatment, introduces several main CCR5 antibodies, and discusses the future strategy of antibody-conjugated nanoparticles including the potential challenges. CCR5 antibodies may be a novel therapy for treating HIV infection effectively and could overcome the limitations of the currently available options.

X-ray crystallographic studies of RoAb13 bound to PIYDIN, a part of the N-terminal domain of C-C chemokine receptor 5.

C-C chemokine receptor 5 (CCR5) is a major co-receptor molecule used by HIV-1 to enter cells. This led to the hypothesis that stimulating an antibody response would block HIV with minimal toxicity. Here, X-ray crystallographic studies of the anti-CCR5 antibody RoAb13 together with two peptides were undertaken: one peptide is a 31-residue peptide containing the PIYDIN sequence and the other is the PIDYIN peptide alone, where PIYDIN is part of the N-terminal region of CCR5 previously shown to be important for HIV entry. In the presence of the longer peptide (the complete N-terminal domain), difference electron density was observed at a site within a hypervariable CDR3 binding region. In the presence of the shorter core peptide PIYDIN, difference electron density is again observed at this CDR3 site, confirming consistent binding for both peptides. This may be useful in the design of a new biomimetic to stimulate an antibody response to CCR5 in order to block HIV infection.