Anti-idiotypic antibodies elicit anti-HIV-1-specific B cell responses

Human anti-HIV-1 broadly neutralizing antibodies (bNAbs) protect against infection in animal models. However, bNAbs have not been elicited by vaccination in diverse wild-type animals or humans, in part because B cells expressing the precursors of these antibodies do not recognize most HIV-1 envelopes (Envs). Immunogens have been designed that activate these B cell precursors in vivo, but they also activate competing off-target responses. Here we report on a complementary approach to expand specific B cells using an anti-idiotypic antibody, iv8, that selects for naive human B cells expressing immunoglobulin light chains with 5–amino acid complementarity determining region 3s, a key feature of anti-CD4 binding site (CD4bs)–specific VRC01-class antibodies. In mice, iv8 induced target cells to expand and mature in the context of a polyclonal immune system and produced serologic responses targeting the CD4bs on Env. In summary, the results demonstrate that an anti-idiotypic antibody can specifically recognize and expand rare B cells that express VRC01-class antibodies against HIV-1.

Source: The Journal of Experimental Medicine - October 6, 2019 Category: Internal Medicine Authors: Dosenovic, P., Pettersson, A.-K., Wall, A., Thientosapol, E. S., Feng, J., Weidle, C., Bhullar, K., Kara, E. E., Hartweger, H., Pai, J. A., Gray, M. D., Parks, K. R., Taylor, J. J., Pancera, M., Stamatatos, L., Nussenzweig, M. C., McGuire, A. T. Tags: Infectious Disease and Host Defense Articles Source Type: research