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

Screening of primary gp120 immunogens to formulate the next generation polyvalent DNA prime-protein boost HIV-1 vaccines.
Author Information (click to view)

Wang S, Wu TH, Hackett A, Efros V, Wang Y, Han D, Wallace A, Chen Y, Hu G, Liu S, Clapham P, Arthos J, Montefiori D, Lu S,


Wang S, Wu TH, Hackett A, Efros V, Wang Y, Han D, Wallace A, Chen Y, Hu G, Liu S, Clapham P, Arthos J, Montefiori D, Lu S, (click to view)

Wang S, Wu TH, Hackett A, Efros V, Wang Y, Han D, Wallace A, Chen Y, Hu G, Liu S, Clapham P, Arthos J, Montefiori D, Lu S,

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Human vaccines & immunotherapeutics 2017 09 21() 0 doi 10.1080/21645515.2017.1380137

Abstract

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 gp70V1V2 antigens expressing V1V2 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.

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