Immunology and Vaccine Development
At the JHMRI a number of researchers are actively working in the area of vaccine immunology and vaccine development.
These studies aim at characterizing the humoral and T-cell mediated mechanisms involved in anti-plasmodial immune responses induced by parasite exposure or after immunization with sub-unit vaccines. A significant effort is dedicate to the evaluation of new vaccine platforms and immunization procedures based on the use synthetic constructs or attenuated microbes. It is expected these studies will help in the development of new innovative vaccine formulations that may greatly help in the development of efficient anti-malaria vaccines to be used for the immunization of human living in malaria endemic areas.
Dr. Rhoel Dinglasan’s laboratory is focused on preclinical development of a mosquito-based malaria transmission-blocking vaccine (mTBV) candidate. The vaccine, formulated with alum, is designed to safely induce a high titer antibody response to a highly conserved anopheline midgut enzyme, alanyl aminopeptidase N (AnAPN1), which mediates malaria parasite establishment in the mosquito vector. Proof-of-concept demonstrations of the potential utility of anti-AnAPN1 antibodies to block transmission of both P. falciparum and P. vivax in diverse anopheline vector species and feasibility studies for mTBV process development were supported by the PATH-Malaria Vaccine Initiative (MVI) and JHMRI. The current NIH funded research program in his lab is focused on developing the next generation AnAPN1 vaccine formulation using a novel virus-like nanoparticle platform.
Dr. Gary Ketner's laboratory is exploring use of adenovirus and adeno-associated virus (AAV) vectors to induce immunity to malaria infection. Approaches under study include use of live recombinant adenovirus recombinants expressing malaria transgenes and/or displaying malaria epitopes on their surfaces to induce conventional immune responses, and use of recombinant AAV vectors to introduce cDNAs encoding protective monoclonal antibodies directly into animals.
Dr. Richard Markham’s laboratory has developed novel DNA and protein vaccine platforms that combine use of an adjuvant with a malaria vaccine construct that directs the malaria antigens in the vaccine to the immature dendritic cells that initiate an immune response. The effectiveness of this approach is demonstrated by challenge studies in immunized mice using transgenic parasites expressing P. falciparum the circumsporozoite protein. These studies demonstrate the ability of this vaccine to provide complete protection, which can be sustained for an extended period. The efficacy of the vaccine appears attributable to its ability to elicit very high concentrations of specific antibody.
Dr. Alan Scott studies the regulation of immunity in the lung and the mechanisms by which antecedent infection or injury influences innate and adaptive responses associated with chronic/progressive pulmonary disease. The Scott lab employs a murine model for the study of the pathogenesis of pulmonary malaria to define the role of lung-resident macrophages and recruited monocytes in the control of malaria-induced lung injury.
Dr. Fidel Zavala’s laboratory studies the role of CD8 T cells against malaria livers stages. The focus of these studies is the characterization of the molecular mechanisms leading to CD8+ T cell differentiation and development of memory T cell populations in the liver. A second focus of this laboratory is the development of transgenic rodent parasites expressing antigens from Plasmodium that infect humans, to develop models for preclinical trials aimed at characterizing immune mechanisms against infection, to evaluate new vaccine platforms and different vaccine strategies .