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

Shixia WangLaboratory of Nucleic Acid Vaccines, Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA

Te-hui ChouLaboratory of Nucleic Acid Vaccines, Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA

Anthony HackettLaboratory of Nucleic Acid Vaccines, Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA

Veronica EfrosLaboratory of Nucleic Acid Vaccines, Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA

Yan WangLaboratory of Nucleic Acid Vaccines, Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA

Dong HanLaboratory of Nucleic Acid Vaccines, Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA

Aaron WallaceLaboratory of Nucleic Acid Vaccines, Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA

Yuxin ChenLaboratory of Nucleic Acid Vaccines, Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA

Guangnan HuLaboratory of Nucleic Acid Vaccines, Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA

Shuying LiuLaboratory of Nucleic Acid Vaccines, Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA

Paul ClaphamDepartment of Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, USA

James ArthosImmunopathogenesis Section, NIAID, NIH, Bethesda, MD, USA

David MontefioriDepartment of Surgery, Duke University School of Medicine, Durham, NC, USA

Shan LuLaboratory of Nucleic Acid Vaccines, Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USACorrespondence[email protected]

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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:

Abbreviations

DP6-001	=	an HIV-1 DNA prime-protein boost vaccine
Env	=	HIV-1 envelope glycoprotein
ELISA	=	enzyme-linked immunosorbent assay
HIV-1	=	human immunodeficiency virus type 1

Disclosure of potential conflicts of interest

No potential conflicts of interest were disclosed.

Funding

This study was supported in part by NIH grants R01 AI065250, 5 U19 AI082676, 5 P01AI082274 and 5R21/R33AI087191, and Bill and Melinda Gates Foundation grant OPP1033112.

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

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

ABSTRACT

Abbreviations

Disclosure of potential conflicts of interest

Funding

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