Mucosal Immunology and Vaccine Development

Biography

Biography: Mehfuz Zaman

Abstract

Group A streptococcus (GAS) infections are extremely important clinical problems due to their global health burden. Rheumatic fever and rheumatic heart disease are responsible for the majority of morbidity and mortality (estimated at 12 million cases annually with 380,000 fatalities). Current leading GAS vaccine candidates are challenged by their limited efficacy against primary GAS infections of the upper respiratory tract (URT) due to lack of mucosal antibody responses. This is due in large part to the lack of human approved mucosal adjuvants. We describe an innovative vaccine strategy to induce mucosal and serum antibodies against GAS in animal models based on an important neutralizing antibody determinant from the cell surface GAS M protein. Incorporation of carrier protein and M protein-based B-cell epitopes onto liposomal vesicles induce potent serum and mucosal antibodies without the need for an additional adjuvant. Immunized mice were capable of preventing GAS infection post-challenge. The size of liposomes influenced the immune response and antigen-specific inflammatory response. Liposomes could be lyophilized to a powder form negating cold-chain storage and stability issues, highlighting the promise to translate from murine studies to application in humans as a vaccine candidate. The study provides important mechanistic insights into how liposomal particulate delivery systems can collectively induce the desired mucosal immune responses to combat GAS infection. The strategy reported here is relevant to the development of subunit mucosal vaccines against other pathogenic organisms.