Our objective is to employ appropriate adjuvants in formulating subunit vaccines to induce protective immunity against Brucella abortus. An analysis will be performed of the immunogenicity of the vaccines and of the immune elements responsible for protection. Protection against B. abortus, a faculative intracellular parasite, requires a combination of cell mediated and humoral immunity. The BALB/c mouse can overcome infection with attenuated B. abortus strain 19 within 2 months, and there vaccination with complexes of B. abortus porin and smooth lipopolysaccharide (LPS) in adjuvants composed of a) muramyl dipeptide (MDP) and trehalose dimycolate; b) MDP and the nonionic block polymer L-121; and c) complexes with the glycoside Quil A (ISCOMS). The latter 2 adjuvants have potential for application to human as well as veterinary vaccines.
Our first aim i s to estabish the cellular and humoral immune mechanism whereby BALB/c mice eliminate strain 19. Quantitative assays will be performed throughout infection of splenic B cells, T cell subsets, activated macrophages, circulation antibodies, and delayed type hypersensitivity. This will be used as the basis for schedules of adoptive and passive transfer experiments to determine the independent and interrelated roles of antibodies and T cell subsets in conferring protection.
Our second aim i s to select subunit vaccines best able to protect mice against challenge infection with strain 19 and to analyze the components of protective immunity. Glycoproteins composed of porin covalently linked to purified O polysaccharide will be evaluated in adjuvants including MDP+L-121 and ISCOMS. The efficacy and duration of protection will be compared with that provided by convalescence from a primary infection. Immune responses induced by the subunit vaccines will be measured quantitatively and the immune elements operative in protective immunity will be established using strain 19 as a standard. This study will provide basic information on the quantitative and qualitative effects of selected adjuvants on both humoral and cell mediated immune responses induced by a bacterial glycoprotein. It will, furthermore, utilize a naturally occurring disease process in which the generation of humoral and cell mediated immune responses relevant to protection can be determined and compared with those brought about by a primary infection.
| Araya, L N; Elzer, P H; Rowe, G E et al. (1989) Temporal development of protective cell-mediated and humoral immunity in BALB/c mice infected with Brucella abortus. J Immunol 143:3330-7 |
