Priming with a Potent HIV-1 DNA Vaccine Frames the Quality of Immune Responses prior to a Poxvirus and Protein Boost

Author:

Asbach Benedikt1,Kibler Karen V.2,Köstler Josef3,Perdiguero Beatriz4,Yates Nicole L.5,Stanfield-Oakley Sherry5,Tomaras Georgia D.5,Kao Shing-Fen6,Foulds Kathryn E.6,Roederer Mario6,Seaman Michael S.7,Montefiori David C.5,Parks Robert5,Ferrari Guido5,Forthal Donald N.8,Phogat Sanjay9,Tartaglia James9,Barnett Susan W.10,Self Steven G.11,Gottardo Raphael11,Cristillo Anthony D.12,Weiss Deborah E.12,Galmin Lindsey12,Ding Song13,Heeney Jonathan L.14,Esteban Mariano4,Jacobs Bertram L.2,Pantaleo Giuseppe15,Wagner Ralf13

Affiliation:

1. Institute of Medical Microbiology and Hygiene, University of Regensburg, Regensburg, Germany

2. Biodesign Institute, Arizona State University, Tempe, Arizona, USA

3. Institute of Clinical Microbiology and Hygiene, University of Regensburg, Regensburg, Germany

4. Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, Madrid, Spain

5. Duke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA

6. Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA

7. Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA

8. Division of Infectious Diseases, Department of Medicine, University of California, Irvine, School of Medicine, Irvine, California, USA

9. Sanofi Pasteur, Swiftwater, Pennsylvania, USA

10. Novartis Vaccines and Diagnostics, Inc., Cambridge, Massachusetts, USA

11. Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, USA

12. Advanced BioScience Laboratories, Inc., Rockville, Maryland, USA

13. EuroVacc Foundation, Lausanne, Switzerland

14. Lab of Viral Zoonotics, Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom

15. Division of Immunology and Allergy, Department of Medicine, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland

Abstract

The evaluation of HIV vaccine efficacy trials indicates that protection would most likely correlate with a polyfunctional immune response involving several effector functions from all arms of the immune system. Heterologous prime-boost regimens have been shown to elicit vigorous T cell and antibody responses in nonhuman primates that, however, qualitatively and quantitatively differ depending on the respective vector systems used. The present study evaluated a DNA prime and poxvirus and protein boost regimen and compared how two poxvirus vectors with various degrees of replication capacity and two different delivery modalities—conventional intramuscular delivery and percutaneous delivery by scarification—impact several immune effectors. It was found that despite the different poxvirus boosts, the overall immune responses in the three groups were similar, suggesting the potent DNA priming as the major determining factor of immune responses. These findings emphasize the importance of selecting optimal priming agents in heterologous prime-boost vaccination settings.

Funder

DAIDS-NIAID-NIH

Bill and Melinda Gates Foundation

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

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