Laboratory of Nucleic Acid Vaccines, Department of Medicine; Program in Molecular Medicine
Immunology of Infectious Disease | Immunoprophylaxis and Therapy
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.
DNA vaccine, HIV-1, antibody, envelope glycoprotein, heterologous prime – boost, polyvalent, protein vaccine, vaccine
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Copyright © 2017 The Author(s). Published with license by Taylor and Francis. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way.
DOI of Published Version
Hum Vaccin Immunother. 2017 Dec 2;13(12):2996-3009. doi: 10.1080/21645515.2017.1380137. Epub 2017 Sep 21. Link to article on publisher's site
Human vaccines and immunotherapeutics
Wang S, Chou T, Hackett A, Efros V, Wang Y, Han D, Wallace A, Chen Y, Hu G, Liu S, Clapham PR, Arthos J, Montefiori D, Lu S. (2017). Screening of primary gp120 immunogens to formulate the next generation polyvalent DNA prime-protein boost HIV-1 vaccines. Open Access Publications by UMMS Authors. https://doi.org/10.1080/21645515.2017.1380137. Retrieved from https://escholarship.umassmed.edu/oapubs/3258
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This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.