Co-immunization of DNA and Protein in the Same Anatomical Sites Induces Superior Protective Immune Responses against SHIV Challenge

Barbara K Felber; Zhongyan Lu; Xintao Hu; Antonio Valentin; Margherita Rosati; Christopher A L Remmel; Joshua A Weiner; Margaret C Carpenter; Katelyn Faircloth; Sherry Stanfield-Oakley; Wilton B Williams; Xiaoying Shen; Georgia D Tomaras; Celia C LaBranche; David Montefiori; Hung V Trinh; Mangala Rao; Munir S Alam; Nathan A Vandergrift; Kevin O Saunders; Yunfei Wang; Wes Rountree; Jishnu Das; Galit Alter; Steven G Reed; Pyone P Aye; Faith Schiro; Bapi Pahar; Jason P Dufour; Ronald S Veazey; Preston A Marx; David J Venzon; George M Shaw; Guido Ferrari; Margaret E Ackerman; Barton F Haynes; George N Pavlakis

doi:10.1016/j.celrep.2020.107624

Co-immunization of DNA and Protein in the Same Anatomical Sites Induces Superior Protective Immune Responses against SHIV Challenge

Cell Rep. 2020 May 12;31(6):107624. doi: 10.1016/j.celrep.2020.107624.

Authors

Barbara K Felber¹, Zhongyan Lu², Xintao Hu², Antonio Valentin³, Margherita Rosati³, Christopher A L Remmel⁴, Joshua A Weiner⁴, Margaret C Carpenter⁴, Katelyn Faircloth⁴, Sherry Stanfield-Oakley⁵, Wilton B Williams⁶, Xiaoying Shen⁶, Georgia D Tomaras⁷, Celia C LaBranche⁸, David Montefiori⁸, Hung V Trinh⁹, Mangala Rao¹⁰, Munir S Alam⁶, Nathan A Vandergrift⁶, Kevin O Saunders⁸, Yunfei Wang⁶, Wes Rountree⁶, Jishnu Das¹¹, Galit Alter¹¹, Steven G Reed¹², Pyone P Aye¹³, Faith Schiro¹³, Bapi Pahar¹³, Jason P Dufour¹³, Ronald S Veazey¹³, Preston A Marx¹⁴, David J Venzon¹⁵, George M Shaw¹⁶, Guido Ferrari⁵, Margaret E Ackerman⁴, Barton F Haynes¹⁷, George N Pavlakis¹⁸

Affiliations

¹ Human Retrovirus Pathogenesis Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702, USA. Electronic address: barbara.felber@nih.gov.
² Human Retrovirus Pathogenesis Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702, USA.
³ Human Retrovirus Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702, USA.
⁴ Thayer School of Engineering, Dartmouth College, Hanover, NH 03755, USA.
⁵ Duke Human Vaccine Institute, Duke University, Durham, NC 27710, USA; Department of Surgery, Duke University, Durham, NC 27710, USA; Department of Molecular Genetics and Microbiology, Duke University, Durham, NC 27710, USA.
⁶ Duke Human Vaccine Institute, Duke University, Durham, NC 27710, USA.
⁷ Duke Human Vaccine Institute, Duke University, Durham, NC 27710, USA; Department of Surgery, Duke University, Durham, NC 27710, USA; Department of Molecular Genetics and Microbiology, Duke University, Durham, NC 27710, USA; Department of Immunology, Duke University, Durham, NC 27710, USA.
⁸ Duke Human Vaccine Institute, Duke University, Durham, NC 27710, USA; Department of Surgery, Duke University, Durham, NC 27710, USA.
⁹ U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD 20817, USA.
¹⁰ U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
¹¹ Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
¹² Infectious Disease Research Institute, Seattle, WA 98102, USA.
¹³ Division of Comparative Pathology, Tulane National Primate Research Center, Covington, LA 70433, USA.
¹⁴ Tulane National Primate Research Center, and Department of Tropical Medicine, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA 70112, USA.
¹⁵ Biostatistics and Data Management Section, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
¹⁶ Departments of Medicine and Microbiology, University of Pennsylvania, Philadelphia, PA 19104, USA.
¹⁷ Duke Human Vaccine Institute, Duke University, Durham, NC 27710, USA; Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA. Electronic address: barton.haynes@duke.edu.
¹⁸ Human Retrovirus Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702, USA. Electronic address: george.pavlakis@nih.gov.

Abstract

We compare immunogenicity and protective efficacy of an HIV vaccine comprised of env and gag DNA and Env (Envelope) proteins by co-administration of the vaccine components in the same muscles or by separate administration of DNA + protein in contralateral sites in female rhesus macaques. The 6-valent vaccine includes gp145 Env DNAs, representing six sequentially isolated Envs from the HIV-infected individual CH505, and matching GLA-SE-adjuvanted gp120 Env proteins. Interestingly, only macaques in the co-administration vaccine group are protected against SHIV CH505 acquisition after repeated low-dose intravaginal challenge and show 67% risk reduction per exposure. Macaques in the co-administration group develop higher Env-specific humoral and cellular immune responses. Non-neutralizing Env antibodies, ADCC, and antibodies binding to FcγRIIIa are associated with decreased transmission risk. These data suggest that simultaneous recognition, processing, and presentation of DNA + Env protein in the same draining lymph nodes play a critical role in the development of protective immunity.

Keywords: ADCC; DNA; FcγR; HIV; Indian rhesus macaques; antibody; cellular immunity; humoral immunity; protein; vaccine.

Published by Elsevier Inc.

Publication types

Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Animals
DNA / genetics*
Humans
Immunization / methods*
Macaca / genetics*
Proteins / genetics*
Simian Immunodeficiency Virus / immunology*

Substances

Proteins
DNA

Abstract

Publication types

MeSH terms

Substances

Grants and funding