Viral Booster Vaccines Improve Mycobacterium bovis BCG-Induced Protection against Bovine Tuberculosis ▿
| Autor: | Paul J. Cockle, Tyler C. Thacker, Adrian V. S. Hill, Zhou Xing, Sarah C. Gilbert, R. Glyn Hewinson, Martin McAulay, H. Martin Vordermeier, Bernardo Villarreal-Ramos, Helen McShane, Shelley G. Rhodes |
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| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Tuberculosis
Immunology Genetic Vectors Immunization Secondary Vaccinia virus Microbiology complex mixtures Severity of Illness Index Adenoviridae chemistry.chemical_compound Immunity medicine Animals Tuberculosis Vaccines Lung Mycobacterium bovis Antigens Bacterial biology Errata business.industry Interleukin-17 Vaccine efficacy medicine.disease biology.organism_classification Virology Vaccination Infectious Diseases chemistry Microbial Immunity and Vaccines Leukocytes Mononuclear Parasitology Cattle Lymph Nodes Vaccinia Tuberculosis vaccines business BCG vaccine Tuberculosis Bovine Acyltransferases |
| Popis: | Previous work with small-animal laboratory models of tuberculosis has shown that vaccination strategies based on heterologous prime-boost protocols using Mycobacterium bovis bacillus Calmette-Guérin (BCG) to prime and modified vaccinia virus Ankara strain (MVA85A) or recombinant attenuated adenoviruses (Ad85A) expressing the mycobacterial antigen Ag85A to boost may increase the protective efficacy of BCG. Here we report the first efficacy data on using these vaccines in cattle, a natural target species of tuberculous infection. Protection was determined by measuring development of disease as an end point after M. bovis challenge. Either Ad85A or MVA85A boosting resulted in protection superior to that given by BCG alone: boosting BCG with MVA85A or Ad85A induced significant reduction in pathology in four/eight parameters assessed, while BCG vaccination alone did so in only one parameter studied. Protection was particularly evident in the lungs of vaccinated animals (median lung scores for naïve and BCG-, BCG/MVA85A-, and BCG/Ad85A-vaccinated animals were 10.5, 5, 2.5, and 0, respectively). The bacterial loads in lymph node tissues were also reduced after viral boosting of BCG-vaccinated calves compared to those in BCG-only-vaccinated animals. Analysis of vaccine-induced immunity identified memory responses measured by cultured enzyme-linked immunospot assay as well as in vitro interleukin-17 production as predictors of vaccination success, as both responses, measured before challenge, correlated positively with the degree of protection. Therefore, this study provides evidence of improved protection against tuberculosis by viral booster vaccination in a natural target species and has prioritized potential correlates of vaccine efficacy for further evaluation. These findings also have implications for human tuberculosis vaccine development. |
| Databáze: | OpenAIRE |
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