Topical gel formulation of broadly neutralizing anti-HIV-1 monoclonal antibody VRC01 confers protection against HIV-1 vaginal challenge in a humanized mouse model

Virology. 2012 Oct 25;432(2):505-10. doi: 10.1016/j.virol.2012.06.025. Epub 2012 Jul 24.

Abstract

The new generation broadly neutralizing antibody VRC01 against HIV-1 shows great potential as a topically administered microbicide to prevent sexual transmission. We evaluated its efficacy in a RAG-hu humanized mouse model of vaginal HIV-1 transmission. Mice were challenged vaginally with R5 tropic HIV-1 BaL an hour after intravaginal application of the VRC01 (1 mg/ml concentration) gel. A combination of four first generation bNAbs, namely b12, 2F5, 4E10 and 2G12, was used as a positive efficacy control whereas a non-specific dengue MAb 4G2 was used as negative control. Our results showed that seven out of nine VRC01 antibody administered mice and all of the mice receiving the four bNAb antibody combination were protected against HIV-1 challenge. These findings demonstrate the efficacy of the new bNAb VRC01 as a topical microbicide to protect against HIV-1 vaginal transmission and highlight the use of the RAG-hu mouse model for testing HIV prevention strategies.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Topical
  • Animals
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal / immunology
  • Antibodies, Neutralizing / administration & dosage*
  • Antibodies, Neutralizing / immunology
  • Chemistry, Pharmaceutical
  • DNA-Binding Proteins
  • Disease Models, Animal*
  • Female
  • Gels / administration & dosage
  • HIV Antibodies / administration & dosage*
  • HIV Antibodies / immunology
  • HIV Infections / immunology
  • HIV Infections / prevention & control*
  • HIV Infections / virology
  • HIV-1 / immunology
  • Homeodomain Proteins
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Vagina / drug effects
  • Vagina / virology*

Substances

  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • DNA-Binding Proteins
  • Gels
  • HIV Antibodies
  • Homeodomain Proteins
  • Rag2 protein, mouse
  • RAG-1 protein