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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Wang, S; Chou, T-H; Hackett, A; Efros, V; Wang, Y; Han, D; Wallace, A; Chen, Y; Hu, G; Liu, S; Clapham, P; Arthos, J; Montefiori, D; Lu, S

Published Date

  • December 2, 2017

Published In

Volume / Issue

  • 13 / 12

Start / End Page

  • 2996 - 3009

PubMed ID

  • 28933684

Pubmed Central ID

  • 28933684

Electronic International Standard Serial Number (EISSN)

  • 2164-554X

Digital Object Identifier (DOI)

  • 10.1080/21645515.2017.1380137

Language

  • eng

Conference Location

  • United States