Priming with DNA Expressing Trimeric HIV V1V2 Alters the Immune Hierarchy Favoring the Development of V2-Specific Antibodies in Rhesus Macaques

Author:

Devasundaram Santhi1,Rosati Margherita2ORCID,Valentin Antonio2,Weiss Svenja3,Itri Vincenza3,Trinh Hung V.45,Bear Jenifer1ORCID,Chowdhury Bhabadeb2,LaBranche Celia C.6ORCID,Montefiori David67,Ferrari Guido678,Rao Mangala4,Kong Xiang-Peng9,Zolla-Pazner Susan3ORCID,Pavlakis George N.2ORCID,Felber Barbara K.1ORCID

Affiliation:

1. Human Retrovirus Pathogenesis Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, Maryland, USA

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

3. Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, New York, USA

4. U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA

5. Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, Maryland, USA

6. Department of Surgery, Duke University, Durham, North Carolina, USA

7. Duke Human Vaccine Institute, Duke University, Durham, North Carolina, USA

8. Department of Molecular Genetics and Microbiology, Duke University, Durham, North Carolina, USA

9. Department of Biochemistry and Molecular Pharmacology, NYU School of Medicine, New York, New York, USA

Abstract

The aim of this work was to design and test a vaccine regimen focusing the immune response on targets associated with infection prevention. We demonstrated that priming with a DNA vaccine expressing only the HIV Env V1V2 region induces Ab responses targeting the critical region in V2 associated with protection. This work shows that V1V2 scaffold DNA priming immunization provides a method to focus immune responses to the desired target region, in the absence of immune interference by other epitopes. This induced immune responses with improved recognition of epitopes important for protective immunity, namely, V2-specific humoral immune responses inversely correlating with HIV risk of infection in the RV144 trial.

Funder

HHS | NIH | National Cancer Institute

HHS | NIH | National Institute of Allergy and Infectious Diseases

Henry M. Jackson Foundation

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

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