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

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

  2. Author Address

    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., Human Retrovirus Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702, USA., Thayer School of Engineering, Dartmouth College, Hanover, NH 03755, USA., 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., Duke Human Vaccine Institute, Duke University, Durham, NC 27710, USA., 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., Duke Human Vaccine Institute, Duke University, Durham, NC 27710, USA; Department of Surgery, Duke University, Durham, NC 27710, USA., 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., U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA., Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA., Infectious Disease Research Institute, Seattle, WA 98102, USA., Division of Comparative Pathology, Tulane National Primate Research Center, Covington, LA 70433, USA., Tulane National Primate Research Center, and Department of Tropical Medicine, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA 70112, USA., Biostatistics and Data Management Section, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA., Departments of Medicine and Microbiology, University of Pennsylvania, Philadelphia, PA 19104, USA., 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., Human Retrovirus Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702, USA. Electronic address: george.pavlakis@nih.gov.,
    1. Year: 2020
    2. Date: May 12
  2. Journal: Cell reports
    1. 31
    2. 6
    3. Pages: 107624
  4. Type of Article: Article
  5. Article Number: 107624
  6. ISSN: 2211-1247
  1. 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 Fc?RIIIa 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. Published by Elsevier Inc.

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External Sources

  1. View Full Text
  2. DOI: 10.1016/j.celrep.2020.107624
  3. PMID: 32402293
  4. View record in Web of Science®
  5. WOS: 000533147000007
  6. PII : S2211-1247(20)30577-5

Library Notes

  1. Fiscal Year: FY2019-2020
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