Technology ID

Dual-Germline Antibody Engager Chimeric HIV–1 Immunogens

Lead Inventor
Zhang, Ping (National Cancer Institute (NCI))
Lusso, Paolo (National Institute of Allergy and Infectious Diseases (NIAID/NIH))
Therapeutic Areas
Infectious Disease
Development Stages
Pre-Clinical (in vitro)
Lead IC

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.

Commercial Applications
  • 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.
Competitive Advantages
  • 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.
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