Manish Sadarangani

The overall goal of my research is to protect children from infections by improving vaccines, vaccination strategies, and building evidence-informed policy and public health initiatives. My research program encompasses laboratory, clinical, and population-based investigations in three complementary focus areas in an innovative molecule-to-population approach.

Focus 1 - Vaccine Development. Develop new highly immunogenic vaccines and a novel vaccine platform.

Focus 2 - Vaccine Immunity. Enhance immunity in individuals by optimizing immune responses to vaccines.

Focus 3 - Vaccine Effectiveness. Improve protection in the population by clinical vaccine evaluation.

Each focus targets a different area in the vaccine cycle, but these are inextricably linked, and my experience and training across methodologies enables me to bring these together in a transformative research program. I have develop­ed the unique repertoire of laboratory, clinical and epidemiologic expertise that is required for a research program in applied, translational vaccinology that will have significant global impact for decades:

Vaccine Development. To develop new highly immunogenic vaccines and a novel delivery system that will induce robust, persistent immunity and can be used with diverse antigens to target antibiotic-resistant pathogens. I have led studies to design new vaccines against S. pneumoniae, Klebsiella and N. meningitidis, using molecular biology, bacterial genetics, microbiology, cellular immunology and animal models. I have designed immunogenic novel vaccines, including one developed to a phase 1 clinical trial. My lab is developing and evaluating pneumococcal and Klebsiella vaccines, aiming to demonstrate immunogenicity and protection in mouse models of human infection and to complete a phase 1 first-in-human clinical trial with at least one novel vaccine.

Vaccine Immunity. To enhance vaccine-induced immunity in individuals by comprehensive understanding of immune responses and optimization by modification of immune responses – towards precision vaccinology. I have evaluated antibody (Ab) and T cell responses to vaccines, including with systems biology approaches. This involved development and use of assays to measure Ab response and Ab function after immunization in humans and mice. We are investigating effects of immune setpoint on responses to new and established vaccines in children, and using mouse models to determine if responses can be improved by manipulation with adju­vants administered before vaccine Ag. If so, it would lead to a new, innovative approach to infant immunization.

Vaccine Effectiveness. To improve vaccine-induced protection in the population by evaluation of vaccines in clinical trials and observational and epidemiological studies of vaccine impact. I have led multicentre national and international phase 1-4 clinical trials and observa­tional studies to evaluate vaccine effectiveness after implementation and across the age spectrum. We assess the full population impact of new and existing vaccines on the incidence and severity of vaccine-preventable diseases, and optimize vaccine schedules for children.