title: DNA and protein co-immunization improves the magnitude and longevity of humoral immune responses in macaques.
abstract: 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.
authors.affiliation: Human Retrovirus Pathogenesis Section, National Cancer Institute, Frederick, Maryland, United States of America.
authors.forename: Rashmi
authors.initials: R
authors.lastname: Jalah
authors.affiliation: Human Retrovirus Pathogenesis Section, National Cancer Institute, Frederick, Maryland, United States of America.
authors.forename: Viraj
authors.initials: V
authors.lastname: Kulkarni
authors.affiliation: Human Retrovirus Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute, Frederick, Maryland, United States of America.
authors.forename: Vainav
authors.initials: V
authors.lastname: Patel
authors.affiliation: Human Retrovirus Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute, Frederick, Maryland, United States of America.
authors.forename: Margherita
authors.initials: M
authors.lastname: Rosati
authors.affiliation: Human Retrovirus Pathogenesis Section, National Cancer Institute, Frederick, Maryland, United States of America.
authors.forename: Candido
authors.initials: C
authors.lastname: Alicea
authors.affiliation: Human Retrovirus Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute, Frederick, Maryland, United States of America.
authors.forename: Jenifer
authors.initials: J
authors.lastname: Bear
authors.affiliation: Institute of Human Virology, Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Lei
authors.initials: L
authors.lastname: Yu
authors.affiliation: Institute of Human Virology, Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Guan
authors.affiliation: Duke Human Vaccine Institute and Departments of Surgery and Immunology, Molecular Genetics and Microbiology, Duke University, Durham, North Carolina, United States of America.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Shen
authors.affiliation: Duke Human Vaccine Institute and Departments of Surgery and Immunology, Molecular Genetics and Microbiology, Duke University, Durham, North Carolina, United States of America.
authors.forename: Georgia D
authors.initials: GD
authors.lastname: Tomaras
authors.affiliation: Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States of America.
authors.forename: Celia
authors.initials: C
authors.lastname: LaBranche
authors.affiliation: Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States of America.
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.affiliation: Public Health Research Institute, University of Medicine and Dentistry of New Jersey, Newark, New Jersey, United States of America.
authors.forename: Rajasekhar
authors.initials: R
authors.lastname: Prattipati
authors.affiliation: Public Health Research Institute, University of Medicine and Dentistry of New Jersey, Newark, New Jersey, United States of America.
authors.forename: Abraham
authors.initials: A
authors.lastname: Pinter
authors.affiliation: AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, United States of America.
authors.forename: Julian
authors.initials: J
authors.lastname: Bess
authors.affiliation: AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, United States of America.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Lifson
authors.affiliation: Infectious Disease Research Institute, Seattle, Washington, United States of America.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Reed
authors.affiliation: Inovio Pharmaceuticals, Inc., Blue Bell, Pennsylvania, United States of America.
authors.forename: Niranjan Y
authors.initials: NY
authors.lastname: Sardesai
authors.affiliation: Biostatistics and Data Management Section, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, United States of America.
authors.forename: David J
authors.initials: DJ
authors.lastname: Venzon
authors.affiliation: Human Retrovirus Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute, Frederick, Maryland, United States of America.
authors.forename: Antonio
authors.initials: A
authors.lastname: Valentin
authors.affiliation: Human Retrovirus Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute, Frederick, Maryland, United States of America.
authors.forename: George N
authors.initials: GN
authors.lastname: Pavlakis
authors.affiliation: Human Retrovirus Pathogenesis Section, National Cancer Institute, Frederick, Maryland, United States of America.
authors.forename: Barbara K
authors.initials: BK
authors.lastname: Felber
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D004279:DNA, Viral / Q000235:genetics; D018274:Electroporation; D005260:Female; D015686:Gene Products, env / Q000276:immunology*; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007074:Immunoglobulin G / Q000276:immunology; D008253:Macaca mulatta; D008297:Male; D018449:SAIDS Vaccines / Q000276:immunology*; D015302:Simian Immunodeficiency Virus; D019444:Vaccines, DNA / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D004279:DNA, Viral; D015686:Gene Products, env; D007074:Immunoglobulin G; D018449:SAIDS Vaccines; D019444:Vaccines, DNA