Robert-Guroff, Marjorie (NCI)
Appella, Daniel (NIDDK)
Helmold Hait, Sabrina (NCI)
Rahman, Mohammed (NCI)
Bissa, Massimiliano (NCI)
Appella, Ettore (NCI)
Jenkins, Lisa Marie (NCI)
Silva De Castro, Isabela (NCI)
Human immunodeficiency virus (HIV) remains a major global health challenge despite the advancement made in development of effective antiretrovirals (ARVs). ARVs are effective at limiting replication and spread of the virus, and progression to acquired immuno-deficiency syndrome (AIDS). However, ARVs often lead to emergence of drug-resistant virus strains insensitive to treatment and with toxic effects following long-term usage. In addition, access to ARVs is limited in certain regions, particularly in sub-Saharan Africa – where the HIV epidemic continues unabated and disproportionately affects women and adolescent girls. There is a global health need for development of alternative approaches providing long-term protection from the virus, such as vaccines.
Researchers at the National Cancer Institute (NCI) previously demonstrated the efficacy of envelope glycoprotein 120 (gp120) variable region 1 (V1)-deleted simian immunodeficiency virus (SIV) vaccines against the highly pathogenic SIVmac251, which recapitulates human AIDS in animals. These SIV envelope V1-deleted vaccines increased the antigenicity of the envelope glycoprotein variable region 2 (V2) and were 65% effective in preventing vaginal SIVmac251 infection in the macaque animal model. However, the vaccine regimen was ineffective in about one third of animals. Therefore, the inventors added the SAMT-247 microbicide that disrupts the folded structure of the viral nucleocapsid protein NCp7 by interfering with zinc coordination in the protein. This resulted in the production of immature viral particles. Following 14 weekly exposures to SIVmac251, 80% of macaques vaccinated and treated with SAMT-247 remained uninfected – reducing infection risk >90%. SAMT-247 was administered 4 hours before each challenge exposure and dramatically augmented vaccine-induced protection via increased NK cytotoxicity, increased monocyte efferocytosis, and decreased T-cell activation (figure below).
NCI is seeking research co-development partners and/or licensees to evaluate, further develop or commercialize this high efficacy vaccine and microbicide combination for use against HIV.
Increased vaccine efficacy of up to 80%
Combination treatment – vaccine and SAMT-247 microbicide – significantly reducing risk of SIV infection
SAMT-247 microbicide is not toxic to human cervical tissue
SAMT-247 microbicide remains effective in cervical mucus
- Development of next generation HIV vaccines
- Prevention of HIV infection and AIDS