Towards the use of CD1 presented mycobacterial lipids in vaccines

Abstract

Diseases caused by mycobacteria, such as tuberculosis humans and ruminants occur worldwide and cause health problem in addition to major economic losses. Vaccines that are currently available, cause problems in diagnosis of other diseases and/or have limited efficacy. Most of the novel vaccine candidates against mycobacterial infections are MHC-presented protein antigens. Lipid, abundant components of mycobacteria, has not yet been considered as antigens to include as subunit in a vaccine against mycobacterial infections. During her doctoral research at the Faculty of Veterinary Medicine in Utrecht University, Thi Kim Anh Nguyen from Vietnam, performed research on inducing immune response against lipids, which may help protect against mycobacteria Unlike proteins, lipid antigens are known to be presented to T cells by CD1, an MHC-I like protein. This thesis describes CD1 restricted immunity against mycobacterial infections in cattle and demonstrates the immune responses of the host to natural mycobacterial infection and to vaccines produced from mycobacterial glycolipid either in separate antigen vaccine or in conjugate with protein vaccine. Initially, this study found that in cattle that are naturally infected with mycobacteria, strong immune responses against bacterial lipids could be detected. It is well known that mycobacterial proteins can induce strong responses, but that lipids perform equally well is a new finding. Experimental mmunization with a model mycobacterial lipid in the absence of mycobacterial infection showed differences between protein and lipid antigens.