Friday, March 14, 2014

(Inovio) DNA and Protein Co-Immunization Improves the Magnitude and Longevity of Humoral Immune Responses in Macaques

Abstract 3/13/2014

We tested the concept of combining DNA with protein to improve anti-HIV Env systemic and mucosal humoral immune responses. Rhesus macaques were vaccinated with DNA, DNA&protein co-immunization or DNA prime followed by protein boost, and the magnitude and mucosal dissemination of the antibody responses were monitored in both plasma and mucosal secretions. We achieved induction of robust humoral responses by optimized DNA vaccination delivered by in vivo electroporation. These responses were greatly increased upon administration of a protein boost. Importantly, a co-immunization regimen of DNA&protein injected in the same muscle at the same time induced the highest systemic binding and neutralizing antibodies to homologous or heterologous Env as well as the highest Env-specific IgG in saliva. Inclusion of protein in the vaccine resulted in more immunized animals with Env-specific IgG in rectal fluids. Inclusion of DNA in the vaccine significantly increased the longevity of systemic humoral immune responses, whereas protein immunization, either as the only vaccine component or as boost after DNA prime, was followed by a great decline of humoral immune responses overtime. We conclude that DNA&protein co-delivery in a simple vaccine regimen combines the strength of each vaccine component, resulting in improved magnitude, extended longevity and increased mucosal dissemination of the induced antibodies in immunized rhesus macaques.

About the Authors

Rashmi Jalah, Viraj Kulkarni, Candido Alicea, Barbara K. Felber
Human Retrovirus Pathogenesis Section, National Cancer Institute, Frederick, Maryland, United States of America
Vainav Patel, Margherita Rosati, Jenifer Bear, Antonio Valentin, George N. Pavlakis
Human Retrovirus Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute, Frederick, Maryland, United States of America
Lei Yu, Yongjun Guan
Institute of Human Virology, Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, United States of America
Xiaoying Shen, Georgia D. Tomaras
Duke Human Vaccine Institute and Departments of Surgery and Immunology, Molecular Genetics and Microbiology, Duke University, Durham, North Carolina, United States of America
Celia LaBranche, David C. Montefiori
Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States of America
Rajasekhar Prattipati, Abraham Pinter
Public Health Research Institute, University of Medicine and Dentistry of New Jersey, Newark, New Jersey, United States of America
Julian Bess Jr, Jeffrey D. Lifson
AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, United States of America
Steven G. Reed
Infectious Disease Research Institute, Seattle, Washington, United States of America
Niranjan Y. Sardesai
Inovio Pharmaceuticals, Inc., Blue Bell, Pennsylvania, United States of America
David J. Venzon
Biostatistics and Data Management Section, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, United States of America

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