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Immunogens for Use in a High Efficacy HIV Vaccine

Summary
Prevention and control of human immunodeficiency virus (HIV) infections require a vaccine providing long-lasting protection. The most promising vaccine up to date consists of a regimen of immunization with genetically engineered HIV proteins, including the surface glycoprotein gp120, with a resulting efficacy of ~30%. Recent evidence indicates antibodies produced against variable envelope region 2 (V2) of gp120 in primates are associated with higher levels of protection, while antibodies produced against variable envelope region 1 (V1) have an opposite and interfering effect. Researchers at the National Cancer Institute (NCI) and New York University (NYU) have developed V1-deleted gp120 immunogens using Simian immunodeficiency virus (SIV), and observed an increase in antibodies against V2 in macaques upon immunization. NCI is seeking parties interested in co-developing and/or licensing V1-deleted gp120 immunogens for their use in an improved HIV vaccine.
NIH Reference Number
E-160-2018
Product Type
Keywords
  • Vaccine, HIV, Human Immunodeficiency Virus, AIDS, Variable Envelope Region, V1, V2, Glycoprotein, Gp120, Franchini
Collaboration Opportunity
This invention is available for licensing and co-development.
Contact
Description of Technology

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.

Potential Commercial Applications
  • Human immunodeficiency virus (HIV) vaccine
Competitive Advantages
  • 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)

 

Inventor(s)

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)

Development Stage
Publications

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]

Patent Status
  • PCT: PCT Application Number 2019/057268, Filed 22 Oct 2018
Therapeutic Area
Updated
Wednesday, June 16, 2021