Potent immune responses and in vitro pro-inflammatory cytokine suppression by a novel adenovirus vaccine vector based on rare human serotype 28

• Published in: Vaccine Vol. 28; no. 35; pp. 5691 - 5702
• Main Authors: Kahl, Christoph A, Bonnell, Jessica, Hiriyanna, Suja, Fultz, Megan, Nyberg-Hoffman, Cassandra, Chen, Ping, King, C. Richter, Gall, Jason G.D
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 09.08.2010; Elsevier; Elsevier Limited
• Subjects: Adenovirus; Adenoviruses, Human - immunology; Adolescent; Adult; Aged; Allergy and Immunology; Animal vaccines; Animals; Antibody Formation; Applied microbiology; Biological and medical sciences; CD8-Positive T-Lymphocytes - immunology; Cell Line; Cytokines - immunology; Deoxyribonucleic acid; DNA; Female; Fundamental and applied biological sciences. Psychology; Genetic Vectors; Genomes; Human vaccine; Humans; Immune system; Immunity, Cellular; Immunogenicity; Influenza; Leukocytes, Mononuclear - immunology; Lymphocytes; Male; Membrane Cofactor Protein - immunology; Mice; Mice, Inbred BALB C; Microbiology; Middle Aged; Miscellaneous; Neutralization Tests; Proteins; Rodents; Seroepidemiologic Studies; Seroprevalence; Studies; United States; Vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Vector; Viral Vaccines - immunology; Virology; Young Adult; Human vaccine; Adenovirus; Vector; Seroprevalence; Human; Adenoviridae; Prevalence; Immune response; Suppression; Cytokine; Serology; Vaccine; Epidemiology; In vitro; Virus; Serotype
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2010.06.050

Abstract Adenovirus vaccine vectors derived from rare human serotypes have been shown to be less potent than serotype 5 (Ad5) at inducing immune responses to encoded antigens. To identify highly immunogenic adenovirus vectors, we assessed pro-inflammatory cytokine expression, binding to the CD46 receptor, and immunogenicity. Species D adenoviruses uniquely suppressed pro-inflammatory cytokines and induced high levels of type I interferon. Thus, it was unexpected that a vector derived from a representative serotype, Ad28, induced significantly higher transgene-specific T cell responses than an Ad35 vector. Prime–boost regimens with Ad28, Ad35, Ad14, or Ad5 significantly boosted T cell and antibody responses. The seroprevalence of Ad28 was confirmed to be <10% in the United States. Together, this shows that a rare human serotype-based vector can elicit strong immune responses, which was not predicted by in vitro results.