Progress in the development of mastitis vaccines

Abstract

Mastitis is a combination of clinical signs caused by the infection of the mammary gland with one or more different micro-organisms. These pathogens have been the subject of vaccine experimentation for almost a century. However, vaccine development has been difficult because the immune response to a natural infection does not protect efficiently against a subsequent infection. Recent advances in both molecular biology and the understanding of bovine immunology have lead to important progress in the generation of more efficient vaccines. In the past two years, reports have been published which described prototype vaccines against Streptococcus uberis, Streptococcus agalactiae, Escherichia coli and Staphylococcus aureus. These vaccines are based either on the use of a bacterial extract which contains antigens from the most common bacterial serotypes, or on purified antigens which may or may not be conjugated to carriers in order to increase their immunological efficiency. However, these vaccines are not yet in common use because of problems associated with their lack of widespread efficiency, their production costs and, in some cases, their stability. In addition, chronic forms of mastitis have been associated with intracellular forms of bacteria that are protected from some immune mechanisms and are often not a reachable target for these vaccines. A more recent strategy is to use DNA expression vector plasmids as vaccines which express virulence-associated antigens in vivo. These plasmids, once introduced into the animal, lead to the activation of both humoral and cellular immune responses to the antigen. The type of plasmid, the route of injection and the inclusion of genetic adjuvants can all be adjusted so as to achieve the type of immune response desired. S. aureus mastitis has been particularly difficult to control and in some areas of the world it causes over 50% of the reported cases of mastitis. S. aureus expresses and secretes a large number of proteins that are essential for the virulence of the bacteria and these have been the focus of recent interest for vaccine production. In the last few years, in order to identify the antigens that can be used to induce a protective immune response by a DNA vaccine in cattle; we have produced a series of plasmids and recombinant proteins that represent some of the major virulence factors of this bacterium. The most promising antigen candidates currently being tested are the bacterial adhesion molecules, the extra-cellular processing enzymes and the extra-cellular quorum sensing molecules. Results demonstrate that high titres of antibodies can be obtained by DNA vaccination, and that these antibodies can have an effect on the clearance of the bacteria. It is expected that the successful composition of an S. aureus vaccine will include a combination of DNA-expressed antigens with a booster injection of either recombinant protein or virally vectored antigen.