Alpha-defensin 5 differentially modulates adenovirus vaccine vectors from different serotypes in vivo

• Published in: PLoS pathogens Vol. 15; no. 12; p. e1008180
• Main Authors: Tartaglia, Lawrence J, Badamchi-Zadeh, Alexander, Abbink, Peter, Blass, Eryn, Aid, Malika, Gebre, Makda S, Li, Zhenfeng, Pastores, Kevin Clyde, Trott, Sebastien, Gupte, Siddhant, Larocca, Rafael A, Barouch, Dan H
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.12.2019; Public Library of Science (PLoS)
• Subjects: A549 Cells; Adaptive immunity; Adenoviridae - genetics; Adenoviridae - immunology; Adenoviruses; alpha-Defensins; Animals; Antigens; Biology and life sciences; CD8 antigen; Defensins; Drug delivery systems; Experiments; Expression vectors; Gene expression; Gene Expression Regulation, Viral - physiology; Genetic Vectors; Humans; Immune response; Immune system; Immunogenicity; Immunoglobulin G; Infections; Innate immunity; Listeria; Lymphocytes; Lymphocytes T; Medical research; Medical schools; Medicine and Health Sciences; Mice; Peptides; Proteins; Research and Analysis Methods; Serotypes; Species; Vaccines; Virology; Viruses; Boston Massachusetts; United States > US
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1008180

Adenoviral vectors have shown significant promise as vaccine delivery vectors due to their ability to elicit both innate and adaptive immune responses. α-defensins are effector molecules of the innate immune response and have been shown to modulate natural infection with adenoviruses, but the majority of α-defensin-adenovirus interactions studied to date have only been analyzed in vitro. In this study, we evaluated the role of α-defensin 5 (HD5) in modulating adenovirus vaccine immunogenicity using various serotype adenovirus vectors in mice. We screened a panel of human adenoviruses including Ad5 (species C), Ad26 (species D), Ad35 (species B), Ad48 (species D) and a chimeric Ad5HVR48 for HD5 sensitivity. HD5 inhibited transgene expression from Ad5 and Ad35 but augmented transgene expression from Ad26, Ad48, and Ad5HVR48. HD5 similarly suppressed antigen-specific IgG and CD8+ T cell responses elicited by Ad5 vectors in mice, but augmented IgG and CD8+ T cell responses and innate cytokine responses elicited by Ad26 vectors in mice. Moreover, HD5 suppressed the protective efficacy of Ad5 vectors but enhanced the protective efficacy of Ad26 vectors expressing SIINFEKL against a surrogate Listeria-OVA challenge in mice. These data demonstrate that HD5 differentially modulates adenovirus vaccine delivery vectors in a species-specific manner in vivo.