|TURSE, JOSHUA - WASHINGTON STATE UNIVERSITY
|BROWN, WENDY - WASHINGTON STATE UNIVERSITY
|NORIMINE, JUNZO - WASHINGTON STATE UNIVERSITY
|PALMER, GUY - WASHINGTON STATE UNIVERSITY
Submitted to: Vaccine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/19/2013
Publication Date: 2/27/2013
Citation: Noh, S.M., Turse, J., Brown, W.C., Norimine, J., Palmer, G.H. 2013. Cross-linking of anaplasma marginale outer membrane proteins enhances immunogenicity, but is not required for protection from challenge. Vaccine. 20(5):651-656.
Interpretive Summary: Anaplasmosis, caused by Anaplasma marginale, is a tick transmitted disease of cattle, which is characterized by severe anemia, fever, and weight loss, and is a production-limiting disease. The methods currently available to control anaplasmosis are inadequate and rely on tick control and treatment of infected animals, both of which are difficult in extensive rearing conditions. Encouragingly, a well-defined group of outer membrane proteins induces protective immunity in cattle. However, both the specific antigenic components as well as the format in which those antigens are presented to the bovine immune system need to be determined in order to develop an economically viable vaccine. This research addresses the later knowledge gap, the vaccine format. It was determined that the proteins components of the vaccine do not need to be linked together to induce a protective immune response. This greatly simplifies vaccine formulation and testing.
Technical Abstract: Prevention of bacterial infections via immunization presents particular challenges. While outer membrane extracts are often protective; they are difficult and expensive to isolate and standardize, and thus often impractical for development and implementation in vaccination programs. In contrast, individual proteins, which are easily adapted for use in subunit vaccines, tend to be poorly protective. Consequently, identification of the specific characteristics of outer membrane-based immunogens, in terms of antigen content and context that are required for protective immunity represents a major gap in knowledge needed for bacterial vaccine development. Using Anaplasma marginale, a persistent tick-borne bacterial pathogen of cattle, as a model, we tested whether membrane context affected immunogenicity and capacity to induce protection using two sets of immunogens. The first immunogen was composed of a complex of outer membrane proteins linked by covalent bonds and known to be protective. The second immunogen was derived directly from the first but the proteins were individualized rather than linked. The antibody response induced by the linked immunogen was much greater than that induced by the unlinked immunogen. However, both immunogens induced protective immunity and an anamnestic response. These findings suggest that individual or combinations of proteins can be successfully tested for the ability to induce protective immunity with less regard for overall membrane context. Once protective antigens are identified, immunogenicity could be enhanced by cross-linking to allow reduced immunogen dose or fewer booster vaccinations.