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

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

Author information

1
a Laboratory of Nucleic Acid Vaccines, Department of Medicine , University of Massachusetts Medical School , Worcester , MA , USA.
2
b Department of Molecular Medicine , University of Massachusetts Medical School , Worcester , MA , USA.
3
c Immunopathogenesis Section, NIAID, NIH , Bethesda , MD , USA.
4
d Department of Surgery , Duke University School of Medicine , Durham , NC , USA.

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 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

PMID:
28933684
PMCID:
PMC5718816
DOI:
10.1080/21645515.2017.1380137
[Indexed for MEDLINE]
Free PMC Article

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