Human immunodeficiency virus (HIV) infections remain a pandemic, most prevalent in Africa and the Americas. Anti-retroviral treatments have been effective in preventing spread of the virus and active outbreaks of acquired immune deficiency syndrome (AIDS). However, the development and deployment of an effective vaccine would provide long-lasting protection and alleviate the need to depend heavily on prevention methods that require continued access and adherence. Immunization with the genetically engineered versions of HIV surface glycoprotein gp120, along with env, gag, pol, has been a promising approach that needs improved efficacy (currently at ~30%).
Researchers at NCI have previously shown the levels and avidity of antibodies against variable envelope region 2 (V2) of gp120 correlate with protection of young macaques against the closely related simian immunodeficiency virus (SIV), while antibodies against V1 have an opposing effect on immunity. To improve the current HIV vaccine efforts, they deleted the V1 region from gp120, while preserving the V2 folded conformation, in a collaboration with researchers at NYU. They demonstrated increased antigenicity of V2 upon V1 deletion, as well as increased binding to soluble CD4 receptors. They further observed higher V2 responses in macaques with V1-deleted gp120 immunogen. Using SIV as a model, they could increase vaccine efficacy to nearly 70%.
The Vaccine Branch is seeking statements of capability or interest from parties interested in licensing this invention to further develop, evaluate, or commercialize V1-deleted immunogens for an improved HIV vaccine.
- Human immunodeficiency virus (HIV) vaccine
- Superior vaccine efficacy up to 70% using the closely related SIV as a model
- Increased antibody recognition of V2 via V1-deleted gp120 immunogens, previously associated with protection from SIV
- Increased V2 responses (in macaques, elicited via V1-deleted gp120 immunogens)
Genoveffa Franchini MD (NCI), Isabela Silva de Castro Ph.D (NCI), Giacomo Gorini Ph.D (NCI), Massimiliano Bissa Ph.D (NCI), Timothy Cardozo M.D. Ph.D (New York University)
Silva de Castro I, et al. Anti-V2 antibodies virus vulnerability revealed by envelope V1 deletion in HIV vaccine candidates. [DOI]
Vaccari M, et al. Adjuvant-dependent innate and adaptive immune signatures of risk of SIVmac251 acquisition. [PMID 27239761]
Gordon SN, et al. Boosting of ALVAC-SIV vaccine-primed macaques with the CD4-SIVgp120 fusion protein elicits antibodies to V2 associated with a decreased risk of SIVmac251 acquisition. [PMID 27591322]
- PCT: PCT Application Number 2019/057268, Filed 22 Oct 2018