Overview of Vaccination Trials for Control of Tuberculosis in Cattle, Wildlife and Humans

Abstract

SummaryVaccination is a key strategy for control of tuberculosis (TB), and considerable progress has been made in the past 5 years to develop improved vaccines for humans and animals, differentiate vaccinated animals from those infected with Mycobacterium bovis and deliver vaccines to wildlife. Studies have moved from testing vaccines in small animal models to clinical trials in humans and from experimental challenge studies in cattle and wildlife to evaluation of vaccines in the field. Candidate vaccines undergoing testing in humans include live mycobacterial vaccines to replace bacille Calmette Gu erin (BCG), subunit vaccines (virus vector or protein) to boost BCG and therapeutic vaccines used as an adjunct to chemotherapy. In cattle, a number of diagnostic tests have been developed and successfully tested for differentiating infected from vaccinated animals, which will facilitate the use of BCG vaccine in cattle. Encouraging results have been obtained from recent field trials in cattle using BCG vaccine to protect against natural exposure to M. bovis. To date, no subunit TB vaccines have induced improved protection compared with that for BCG, but prime-boost combinations of BCG with DNA, protein or virus-vectored vaccines have induced better protection than BCG vaccine alone. Development of an oral bait BCG formulation has demonstrated the practicality of delivering TB vaccines to wildlife. Oral BCG preparations have induced protection against experimental challenge of M. bovis in possums, badgers, wild boar and white-tailed deer and against natural exposure to M. bovis in possums. Recent progress in TB vaccine development has provided much impetus for their future use.

Effect of the inoculation site of bovine purified protein derivative (PPD) on the skin fold thickness increase in cattle from officially tuberculosis free and tuberculosis-infected herds

“…This zoonotic disease affects cattle worldwide, causing economic losses due to the costs of implementation of eradication programs, trade limitations, and slaughter of positive animals (Pollock and Neill, 2002;Reviriego Gordejo and Vermeersch, 2006). Control and/or eradication programs worldwide are based on test-and-slaughter policy, due to the unavailability of effective vaccines (Buddle et al, 2013). The infection triggers predominantly a cell-mediated immunity (CMI) during early and intermediate phases of the infection, lead primarily by Th1 lymphocytes (Fifis et al, 1994;Barlow et al, 1997;Pollock and Andersen, 1997;Pollock et al, 2001Pollock et al, , 2005.…”

Applications of bacillus Calmette–Guerin and recombinant bacillus Calmette–Guerin in vaccine development and tumor immunotherapy

“…BCG is one of the most widely used human vaccines, being administered over 4 billion times [18]. It was developed by Albert Calmette and Camille Guerin in France between 1908 and 1921 from a virulent M. bovis strain, with more than 230 serial passages in vitro [19].…”

“…This can be readily addressed now by region-specific vaccine delivery. A major reason for the discontinuation of oral BCG vaccine is that when concentrated BCG vaccine is not swallowed, but drained into the cervical lymph nodes, a high frequency of lymphadenitis developed in children [18]. This will also not likely be an issue now if the vaccines are given to adults in well-designed coated capsules.…”

Display of Antigens on Polyester Inclusions Lowers the Antigen Concentration Required for a Bovine Tuberculosis Skin Test

“…Development of a more specific skin test reagent would be highly desirable. The use of BCG vaccine alone or as part of a heterologous prime-boost combination is currently being considered by a number of countries for control of bovine TB (3). BCG cannot be used currently, as it compromises interpretation of the tuberculin skin test, and development of a test to differentiate infected from vaccinated animals (DIVA) would be essential.…”