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Villarreal-Ramos B.,Bovine TB | Berg S.,Bovine TB | Chamberlain L.,Bovine TB | McShane H.,University of Oxford | And 3 more authors.
Vaccine | Year: 2014

Vaccination is being considered as part of a sustainable strategy for the control of bovine tuberculosis (BTB) in the UK. The live attenuated Mycobacterium bovis bacillus Calmette-Guerin (BCG) has been used experimentally to vaccinate cattle against BTB. However, BCG confers partial protection against BTB and therefore, there is a need to develop improved vaccines. BTB vaccine efficacy experiments require the use of biosafety level 3 facilities which are expensive to maintain, generally oversubscribed and represent a bottle neck for the testing of vaccine candidates. One indicator of the induction of protective responses would be the ability of the host's immune response to control/kill mycobacteria. In this work we have evaluated an intranodal BCG challenge for the selection of vaccine candidates at biosafety level 2 which are capable of inducing mycobactericidal responses. To our knowledge, this is the first such report. Whilst BCG only confers partial protection, it is still the standard against which other vaccines are judged. Therefore we tested the BCG intranodal challenge in BCG (Danish strain) vaccinated cattle and showed that vaccinated cattle had lower BCG cfu counts than naïve cattle at 14 and 21 days after intranodal challenge with BCG (Tokyo strain). This model could help prioritize competing TB vaccine candidates and exploration of primary and secondary immune responses to mycobacteria. © 2014. Source


Dean G.,Bovine TB | Whelan A.,Bovine TB | Whelan A.,UK Defence Science and Technology Laboratory | Clifford D.,Bovine TB | And 7 more authors.
Vaccine | Year: 2014

There is a requirement for vaccines or vaccination strategies that confer better protection against TB than the current live attenuated Mycobacterium bovis Bacillus Calmette-Guerin (BCG) vaccine for use in cattle. Boosting with recombinant viral vectors expressing mycobacterial proteins, such as Ag85A, has shown a degree of promise as a strategy for improving on the protection afforded by BCG. Experiments in small animal models have indicated that broadening the immune response to include mycobacterial antigens other than Ag85A, such as Rv0288, induced by boosting with Ad5 constructs has a direct effect on the protection afforded against TB. Here, we compared the immunogenicity and protection against challenge with M. bovis afforded by boosting BCG-vaccinated cattle with a human type 5 (Ad5)-based vaccine expressing the mycobacterial antigens Ag85A (Ad5-85A); or Ag85A, Rv0251, Rv0287 and Rv0288 (Ad5-TBF); or with protein TBF emulsified in adjuvant (Adj-TBF). Boosting with TBF broaden the immune response. The kinetics of Ad5-TBF and Adj-TBF were shown to be different, with effector T cell responses from the latter developing more slowly but being more durable than those induced by Ad5-TBF. No increase in protection compared to BCG alone was afforded by Ad5-TBF or Adj-TBF by gross pathology or bacteriology. Using histopathology, as a novel parameter of protection, we show that boosting BCG vaccinated cattle with Ad5-85A induced significantly better protection than BCG alone. © 2013. Source


Villarreal-Ramos B.,Bovine TB | Berg S.,Bovine TB | Chamberlain L.,Bovine TB | McShane H.,Roosevelt University | And 3 more authors.
Vaccine | Year: 2014

Vaccination is being considered as part of a sustainable strategy for the control of bovine tuberculosis (BTB) in the UK. The live attenuated Mycobacterium bovis bacillus Calmette-Guerin (BCG) has been used experimentally to vaccinate cattle against BTB. However, BCG confers partial protection against BTB and therefore, there is a need to develop improved vaccines. BTB vaccine efficacy experiments require the use of biosafety level 3 facilities which are expensive to maintain, generally oversubscribed and represent a bottle neck for the testing of vaccine candidates. One indicator of the induction of protective responses would be the ability of the host's immune response to control/kill mycobacteria. In this work we have evaluated an intranodal BCG challenge for the selection of vaccine candidates at biosafety level 2 which are capable of inducing mycobactericidal responses. To our knowledge, this is the first such report. Whilst BCG only confers partial protection, it is still the standard against which other vaccines are judged. Therefore we tested the BCG intranodal challenge in BCG (Danish strain) vaccinated cattle and showed that vaccinated cattle had lower BCG cfu counts than naïve cattle at 14 and 21 days after intranodal challenge with BCG (Tokyo strain). This model could help prioritize competing TB vaccine candidates and exploration of primary and secondary immune responses to mycobacteria. Crown Copyright © 2014. Source


Dean G.,Bovine TB | Clifford D.,Bovine TB | Gilbert S.,University of Oxford | McShane H.,University of Oxford | And 3 more authors.
Veterinary Immunology and Immunopathology | Year: 2014

BCG is used experimentally as a vaccine against tuberculosis (TB), induced by Mycobacterium bovis, in cattle (bTB). However, the efficacy of BCG is variable in humans, cattle and guinea pigs. An adenoviral vector expressing Antigen 85A (Ad5Ag85A) has enhanced protection against TB in mice when used in combination with BCG for prime-boost experiments. However, the route of immunisation affects the degree of protection seen. This work examines the immunogenicity of a new vectored vaccine (Ad5-TBF) that expresses Ag85A, Rv0287, Rv0288 and Rv0251c to explore the effects of dose of adenoviral boost and route of inoculation on immunogenicity. We found that 2×109 infectious units (iu) delivered intradermally conferred the most consistent and strongest responses of the different regimes tested. © 2014 . Source

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