Novel chimpanzee adenovirus-vectored respiratory mucosal tuberculosis vaccine: overcoming local anti-human adenovirus immunity for potent TB protection
| Autor: | Daniela Damjanovic, Hildegund C.J. Ertl, Jack Gauldie, X-D Yao, Xueya Feng, Kenneth L. Rosenthal, Rocky Lai, Sam Afkhami, Niroshan Thanthrige-Don, Anna Zganiacz, M Fe Medina, Zhou Xing, Mangalakumari Jeyanathan |
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| Rok vydání: | 2015 |
| Předmět: |
Pan troglodytes
viruses Genetic Vectors Immunology Chimpanzee adenovirus Enzyme-Linked Immunosorbent Assay Adenoviridae Mice Immunity Animals Humans Immunology and Allergy Medicine Respiratory system Tuberculosis Vaccines Tuberculosis Pulmonary Mice Inbred BALB C business.industry Flow Cytometry Antibodies Bacterial Antibodies Neutralizing Virology Disease Models Animal business Tuberculosis vaccines |
| Zdroj: | Mucosal Immunology. 8:1373-1387 |
| ISSN: | 1933-0219 |
| DOI: | 10.1038/mi.2015.29 |
| Popis: | Pulmonary tuberculosis (TB) remains to be a major global health problem despite many decades of parenteral use of Bacillus Calmette-Guérin (BCG) vaccine. Developing safe and effective respiratory mucosal TB vaccines represents a unique challenge. Over the past decade or so, the human serotype 5 adenovirus (AdHu5)-based TB vaccine has emerged as one of the most promising candidates based on a plethora of preclinical and early clinical studies. However, anti-AdHu5 immunity widely present in the lung of humans poses a serious gap and limitation to its real-world applications. In this study we have developed a novel chimpanzee adenovirus 68 (AdCh68)-vectored TB vaccine amenable to the respiratory route of vaccination. We have evaluated AdCh68-based TB vaccine for its safety, T-cell immunogenicity, and protective efficacy in relevant animal models of human pulmonary TB with or without parenteral BCG priming. We have also compared AdCh68-based TB vaccine with its AdHu5 counterpart in both naive animals and those with preexisting anti-AdHu5 immunity in the lung. We provide compelling evidence that AdCh68-based TB vaccine is not only safe when delivered to the respiratory tract but, importantly, is also superior to its AdHu5 counterpart in induction of T-cell responses and immune protection, and limiting lung immunopathology in the presence of preexisting anti-AdHu5 immunity in the lung. Our findings thus suggest AdCh68-based TB vaccine to be an ideal candidate for respiratory mucosal immunization, endorsing its further clinical development in humans. |
| Databáze: | OpenAIRE |
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