Antibody responses to prime–boost vaccination with an HIV-1 gp145 envelope protein and chimpanzee adenovirus vectors expressing HIV-1 gp140. (23rd October 2016)

• Record Type: Journal Article
• Authors: Emmer, Kristel L.; Wieczorek, Lindsay; Tuyishime, Steven; Molnar, Sebastian; Polonis, Victoria R.; Ertl, Hildegund C.J.
• Is Part Of: AIDS. Volume 30:Number 16(2016)
• Publication Date: 2016-10-23
• Subjects: adenovirus vector -- antibodies -- envelope proteins -- HIV-1 -- neutralization -- vaccine; AIDS (Disease) -- Periodicals; Acquired Immunodeficiency Syndrome; AIDS (Disease); Periodicals; Periodicals; 616.9792005
• DOI: 10.1097/QAD.0000000000001224
• Languages: English
• ISSNs: 0269-9370

Abstract

Abstract : Objectives: Over 2 million individuals are infected with HIV type 1 (HIV-1) each year, yet an effective vaccine remains elusive. The most successful HIV-1 vaccine to date demonstrated 31% efficacy. Immune correlate analyses associated HIV-1 envelope (Env)-specific antibodies with protection, thus providing a path toward a more effective vaccine. We sought to test the antibody response from novel prime–boost vaccination with a chimpanzee-derived adenovirus (AdC) vector expressing a subtype C Env glycoprotein (gp)140 combined with either a serologically distinct AdC vector expressing gp140 of a different subtype C isolate or an alum-adjuvanted, partially trimeric gp145 from yet another subtype C isolate. Design: Three different prime–boost regimens were tested in mice: AdC prime–protein boost, protein prime–AdC boost, and AdC prime–AdC boost. Each regimen was tested at two different doses of AdC vector in a total of six experimental groups. Methods: Sera were collected at various time points and evaluated by ELISA for Env-specific antibody binding, isotype, and avidity. Antibody functionality was assessed by pseudovirus neutralization assay. Results: Priming with AdC followed by a protein boost or sequential immunizations with two AdC vectors induced HIV-1 Env-specific binding antibodies, including those to the variable region 2, whereas priming with protein followed by an AdC boost was relatively ineffective. Antibodies that cross-neutralized tier 1 HIV-1 from different subtypes were elicited with vaccine regimens that included immunizations with protein. Conclusion: Our study warrants further investigation of AdC vector and gp145 protein prime–boost vaccines and their ability to protect against acquisition in animal challenge studies. Abstract : Supplemental Digital Content is available in the text