Screening of primary gp120 immunogens to formulate the next generation polyvalent DNA prime-protein boost HIV-1 vaccines

Hum Vaccin Immunother. 2017 Dec 2;13(12):2996-3009. doi: 10.1080/21645515.2017.1380137. Epub 2017 Sep 21.


Our previous preclinical studies and a Phase I clinical trial DP6-001 have indicated that a polyvalent Env formulation was able to elicit broadly reactive antibody responses including low titer neutralizing antibody responses against viral isolates of subtypes A, B, C and AE. In the current report, a panel of 62 gp120 immunogens were screened in a rabbit model to identify gp120 immunogens that can elicit improved binding and neutralizing antibody responses and some of them can be included in the next polyvalent formulation. Only about 19% of gp120 immunogens in this panel were able to elicit neutralizing antibodies against greater than 50% of the viruses included in a high throughput PhenoSense neutralization assay when these immuongens were tested as a DNA prime followed by a fixed 5-valent gp120 protein vaccine boost. The new polyvalent formulation, using five gp120 immunogens selected from this subgroup, elicited improved quality of antibody responses in rabbits than the previous DP6-001 formulation. More significantly, this new polyvalent formulation elicited higher antibody responses against a panel of gp70V1/V2 antigens expressing V1/V2 sequences from diverse subtypes. Bioinformatics analysis supports the design of a 4-valent or 5-valent formulation using gp120 immunogens from this screening study to achieve a broad coverage against 16 HIV-1 subtypes.

Keywords: DNA vaccine; HIV-1; antibody; envelope glycoprotein; heterologous prime – boost; polyvalent; protein vaccine; vaccine.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS Vaccines / administration & dosage
  • AIDS Vaccines / genetics
  • AIDS Vaccines / immunology*
  • Animals
  • Antibodies, Neutralizing / blood*
  • Drug Evaluation, Preclinical
  • HIV Antibodies / blood*
  • HIV Envelope Protein gp120 / genetics
  • HIV Envelope Protein gp120 / immunology*
  • Immunization Schedule
  • Neutralization Tests
  • Rabbits
  • Vaccines, DNA / administration & dosage
  • Vaccines, DNA / genetics
  • Vaccines, DNA / immunology*
  • Vaccines, Subunit / administration & dosage
  • Vaccines, Subunit / genetics
  • Vaccines, Subunit / immunology


  • AIDS Vaccines
  • Antibodies, Neutralizing
  • HIV Antibodies
  • HIV Envelope Protein gp120
  • Vaccines, DNA
  • Vaccines, Subunit
  • gp120 protein, Human immunodeficiency virus 1