Screening of primary gp120 immunogens to formulate the next generation polyvalent DNA prime-protein boost HIV-1 vaccines.
Journal Article (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
- PMC5718816
Electronic International Standard Serial Number (EISSN)
- 2164-554X
Digital Object Identifier (DOI)
- 10.1080/21645515.2017.1380137
Language
- eng
Conference Location
- United States