Dual-Germline Antibody Engager Chimeric HIV–1 Immunogens
Despite four decades of intensive research, a safe and effective HIV-1 vaccine remains elusive due to the extreme difficulty in eliciting broadly neutralizing antibodies (bNAbs), which recognize and block HIV-1 from entering healthy cells. Only rare natural HIV-1 envelopes (Envs) promote the activation and expansion of naive B cells expressing unmutated germline antibodies of various bNAb lineages, but they typically do so for a single lineage for the same neutralization site. To overcome this challenge, NIAID has designed and characterized two chimeric HIV-1 Env immunogens capable of simultaneously engaging multiple germline bNAb lineages. Both chimeric Env immunogens maintain native-like folding and engage two lineages of germline bNAbs directed against two independent sites of HIV–1 vulnerability.
- Immunization: The dual-germline engager HIV–1 immunogens could be employed during the priming phase of an HIV vaccine to trigger multiple bNAb lineages simultaneously, resulting in a multi-target protective antibody response.
- Clinical Treatment: The dualgermline engager HIV–1 immunogens could serve as an alternative to current anti-retrovirals or incorporated into current HIV treatment strategies.
- Dual-germline engager HIV–1 Env immunogens are inherently superior to the currently available single-germlineengagers for eliciting bNAbs.
- The chimeric design could be expanded to generate HIV–1 Env trimers with even more germline bNAbspecificities to enable a broader immunogenic response against HIV.