Journal article
Type I IFN Induced by Adenovirus Serotypes 28 and 35 Has Multiple Effects on T Cell Immunogenicity
The Journal of immunology (1950), v 188(12), pp 6109-6118
15 Jun 2012
PMID: 22586038
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Recombinant adenovirus (rAd) vectors are being investigated as vaccine delivery vehicles in preclinical and clinical studies. rAds constructed from different serotypes differ in receptor usage, tropism, and ability to activate cells, aspects of which likely contribute to their different immunogenicity profiles. In this study, we compared the infectivity and cell stimulatory capacity of recombinant adenovirus serotype 5 (rAd5), recombinant adenovirus serotype 28 (rAd28), and recombinant adenovirus serotype 35 (rAd35) in association with their respective immunogenicity profiles. We found that rAd28 and rAd35 infected and led to the in vitro maturation and activation of both human and mouse dendritic cells more efficiently compared with rAd5. In stark contrast to rAd5, rAd28 and rAd35 induced production of IFN-alpha and stimulated IFN-related intracellular pathways. However, the in vivo immunogenicity of rAd28 and rAd35 was significantly lower than that of rAd5. Deletion of IFN-alpha signaling during vaccination with rAd28 and rAd35 vectors increased the magnitude of the insert-specific T cell response to levels induced by vaccination with rAd5 vector. The negative impact of IFN-alpha signaling on the magnitude of the T cell response could be overcome by increasing the vaccine dose, which was also associated with greater polyfunctionality and a more favorable long-term memory phenotype of the CD8 T cell response in the presence of IFN-alpha signaling. Taken together, our results demonstrate that rAd-induced IFN-alpha production has multiple effects on T cell immunogenicity, the understanding of which should be considered in the design of rAd vaccine vectors. The Journal of Immunology, 2012, 188: 6109-6118.
Metrics
Details
- Title
- Type I IFN Induced by Adenovirus Serotypes 28 and 35 Has Multiple Effects on T Cell Immunogenicity
- Creators
- Matthew J. Johnson - NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USAConstantinos Petrovas - Vaccine Research CenterTakuya Yamamoto - Vaccine Research CenterRoss W. B. Lindsay - International AIDS Vaccine InitiativeKarin Lore - Karolinska InstitutetJason G. D. Gall - GenVecEmma Gostick - Cardiff UniversityFrancois Lefebvre - Vaccine & Gene Therapy Institute of FloridaMark J. Cameron - Vaccine & Gene Therapy Institute of FloridaDavid A. Price - Cardiff UniversityElias Haddad - Vaccine & Gene Therapy Institute of FloridaRafick-Pierre Sekaly - Vaccine & Gene Therapy Institute of FloridaRobert A. Seder - Vaccine Research CenterRichard A. Koup - Vaccine Research Center
- Publication Details
- The Journal of immunology (1950), v 188(12), pp 6109-6118
- Publisher
- American Association of Immunologists
- Number of pages
- 10
- Grant note
- ZIAAI005073 / NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- College of Medicine; Infectious Diseases (and HIV Medicine); Drexel University
- Web of Science ID
- WOS:000305077900036
- Scopus ID
- 2-s2.0-84862621203
- Other Identifier
- 991020111096604721
UN Sustainable Development Goals (SDGs)
This publication has contributed to the advancement of the following goals:
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Collaboration types
- Industry collaboration
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Immunology