HIV Glycoprotein 36 [Gold]

Twenty-five 13- to 35-amino-acid-long peptides representing regions of human immunodeficiency virus type 2 (HIV-2), strain SBL6669, envelope proteins were evaluated for their immunogenic activity in guinea pigs. The peptides were selected to provide homologous representation of sites in the HIV-1 envelope proteins that were previously documented to have a particular immunogenic importance. A number of the HIV-2 peptides were found to be capable of inducing strain SBL6669 neutralizing and antibody-dependent cellular cytotoxicity (ADCC) antibodies. Two overlapping peptides covering amino acids 311-337 representing the central and C-terminal part of the variable third (V3) region, terminology according to Modrow et al. [Modrow, S., Hahn, B., Shaw, G. M., Gallo, R. C., Wong-Staal, F. & Wolf, H. (1987) J. Virol. 61, 570-5781, showed the most pronounced capacity to induce neutralizing antibodies. One of the peptides (amino acids 318-337) also induced antibodies mediating ADCC. Two additional regions in the large glycoprotein, gpl25, containing linear sites reacting with neutralizing antibodies were identified (amino acids 119-137 and 472-509). The transmembrane protein, gp36, of HIV-2 harbored two regions of importance for induction of neutralizing antibodies (amino acids 595-614 and 714-729). ADCC activity was induced by two additional gpl25-specific peptides (amino acids 291-311 and 446-461). Thus, except for the single V3-specific site there was no correlation between linear immunogenic sites stimulating neutralizing antibody and ADCC activity. These findings pave the way for development of synthetic vaccines against HIV-2 and possibly also simian immunodeficiency virus infections. The capacity of such a product to induce protective immunity can be evaluated in macaque monkeys.

Objective: The ability to induce neutralizing antibodies may be the most important feature of an antiretroviral vaccine, preventing infection of target cells and subsequent integration of the virus into the cellular genome where the virus may persist. Broadly neutralizing antibodies directed against conserved epitopes in the membrane proximal external region (MPER) of the transmembrane envelope (TM) protein gp41 of HIV-1 such as the monoclonal antibodies (mAb) 2F5 and mAb 4E10 have been found in infected individuals; however, all attempts to induce such antibodies failed. In individuals infected with HIV-2 such antibodies were not yet reported. Methods: Two recombinant proteins corresponding to the ectodomain of the TM protein gp36 of HIV-2 were produced, rats were immunized and sera were analyzed for binding and neutralizing antibodies. Results: Although binding antibodies were induced, none of the sera neutralized HIV-2. Most interestingly, epitope mapping showed specific binding of the antibodies to the MPER of gp36, to a region homologous to the binding site of the mAb 4E10 in gp41 of HIV-1. Conclusions: Although MPER-specific antibodies were induced by vaccination with gp36, these antibodies did not neutralize HIV-2. This is similar to the situation with HIV-1, but in contrast to that with gammaretroviruses. Copyright (C) 2011 S. Karger AG, Basel