The immunogenicity of an HIV-1 gag conserved element DNA vaccine in people with HIV and receiving antiretroviral therapy-Reference-Cited by-同舟云学术

The immunogenicity of an HIV-1 gag conserved element DNA vaccine in people with HIV and receiving antiretroviral therapy

Published:2023-12-04 Issue: Volume: Page:
ISSN:0269-9370
Container-title:AIDS
language:en
Short-container-title:

Author:

Jacobson Jeffrey M.¹,Felber Barbara K.²,Chen Huichao³,Pavlakis George N.⁴,Mullins James I.⁵,de Rosa Stephen C.⁶,Kuritzkes Daniel R.⁷,Tomaras Georgia D.⁸,Kinslow Jennifer⁹,Bao Yajing³,Olefsky Maxine³,Rosati Margherita⁴,Bear Jenifer²,Hannaman Drew¹⁰,Laird Gregory M.¹¹,Cyktor Joshua C.¹²,Heath Sonya L.¹³,Collier Ann C.¹⁴,Koletar Susan L.¹⁵,Taiwo Babafemi O.¹⁶,Tebas Pablo¹⁷,Wohl David A.¹⁸,belanzauran-Zamudio Pablo F.¹⁹,Mcelrath M. Juliana⁶,Landay Alan L.⁹

Affiliation:

1. Division of Infectious Diseases, Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH

2. Human Retrovirus Pathogenesis Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD

3. Harvard T.H. Chan School of Public Health, Boston, MA

4. Human Retrovirus Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD

5. Departments of Microbiology, Medicine, and Global Health, University of Washington

6. Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA

7. Division of Infectious Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA

8. Duke Center for Human Systems Immunology, Departments of Surgery, Immunology, Molecular Genetics and Microbiology, Durham, NC

9. Department of Internal Medicine, Rush University Medical Center, Chicago, IL

10. Ichor Medical Systems, San Diego, CA

11. Accelevir Diagnostics, Baltimore, MD

12. Division of Infectious Diseases, University of Pittsburgh, Pittsburgh, PA

13. Division of Infectious Disease, University of Alabama at Birmingham, Birmingham, AL

14. Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle

15. Division of Infectious Diseases, College of Medicine, The Ohio State University, Columbus, OH

16. Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, IL

17. Division of Infectious Diseases, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA

18. Division of Infectious Diseases, Department of Medicine, The University of North Carolina School of Medicine, NC

19. Contractor, Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

Abstract

Objective: The primary objective of the study was to assess the immunogenicity of an HIV-1 Gag conserved element DNA vaccine (p24CE DNA) in people with HIV (PWH) receiving suppressive antiretroviral therapy (ART). Design: AIDS Clinical Trials Group A5369 was a phase I/IIa, randomized, double-blind, placebo-controlled study of PWH receiving ART with plasma HIV-1 RNA less than 50 copies/ml, current CD4+ T-cell counts greater than 500 cells/μl, and nadir CD4+ T-cell counts greater than 350 cells/μl. Methods: The study enrolled 45 participants randomized 2 : 1 : 1 to receive p24CE DNA vaccine at weeks 0 and 4, followed by p24CE DNA admixed with full-length p55Gag DNA vaccine at weeks 12 and 24 (arm A); full-length p55Gag DNA vaccine at weeks 0, 4, 12, and 24 (arm B); or placebo at weeks 0, 4, 12, and 24 (arm c). The active and placebo vaccines were administered by intramuscular electroporation. Results: There was a modest, but significantly greater increase in the number of conserved elements recognized by CD4+ and/or CD8+ T cells in arm A compared with arm C (P = 0.014). The percentage of participants with an increased number of conserved elements recognized by T cells was also highest in arm A (8/18, 44.4%) vs. arm C (0/10, 0.0%) (P = 0.025). There were no significant differences between treatment groups in the change in magnitude of responses to total conserved elements. Conclusion: A DNA-delivered HIV-1 Gag conserved element vaccine boosted by a combination of this vaccine with a full-length p55Gag DNA vaccine induced a new conserved element-directed cellular immune response in approximately half the treated PWH on ART.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Infectious Diseases,Immunology,Immunology and Allergy