UMMS Affiliation
Laboratory of Nucleic Acid Vaccines, Department of Medicine; Program in Molecular Medicine
Publication Date
2017-12-02
Document Type
Article
Disciplines
Immunology of Infectious Disease | Immunoprophylaxis and Therapy
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
Rights and Permissions
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
10.1080/21645515.2017.1380137
Source
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
Journal/Book/Conference Title
Human vaccines and immunotherapeutics
Related Resources
PubMed ID
28933684
Repository Citation
Wang, Shixia; Chou, Te-Hui; Hackett, Anthony; Efros, Veronica; Wang, Yan; Han, Dong; Wallace, Aaron; Chen, Yuxin; Hu, Guangnan; Liu, Shuying; Clapham, Paul R.; Arthos, James; Montefiori, David; and Lu, Shan, "Screening of primary gp120 immunogens to formulate the next generation polyvalent DNA prime-protein boost HIV-1 vaccines" (2017). Open Access Articles. 3258.
https://escholarship.umassmed.edu/oapubs/3258
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.