In humans, malaria parasite grows and multiplies first in the liver cells and then in the Red Blood Cells (RBCs). And it is the blood stage of the parasite life cycle, which is responsible for the clinical signs and symptoms of malaria. During the blood stage cycle Plasmodium merozoites invade and multiply within RBCs. The invasion of red cells by malaria parasites is a complex process that involves a series of specific molecular interactions between parasite proteins and red cell receptors that mediate different steps in the invasion process. It is expected that a blood stage malaria vaccine, which will block these receptor ligand interactions will have the potential to prevent clinical disease and decrease severity of an established infection. Research identifying these various families of parasite proteins has been supported by Department of Biotechnology (DBT).
International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi along with its translational research partner “Multi Vaccines Development Program” earlier known as “Malaria Vaccine Development Program” (a not-for-profit society formed and registered under the Societies Registration Act) has advanced the development of blood-stage vaccines for P. falciparum and P. vivax malaria over the last decade. Funding support through Vaccine Grand Challenge Program of Department of Biotechnology, Biotechnology Industry Research Assistance Council (BIRAC) and multiple international agencies including Malaria Vaccine Initiative (MVI), PATH and European Vaccine Initiative (EVI) has been received.
These recombinant protein-based adjuvanted malaria vaccines advanced through the translational development pathway of GMP production, pre-clinical immunogenicity testing, GLP compliant toxicity testing and Phase I trial after receiving all necessary regulatory approvals. All these translational development activities have been done with Indian partners or collaborators or through an out-sourced model. A brief of the three vaccine candidates, which have undergone development beyond lab bench are mentioned below:
JAIVAC-1 (P. falciparum vaccine candidate)
JAIVAC-1, the first malaria vaccine to undergo a clinical trial in India is composed of a physical mixture of two recombinant proteins, namely, PfMSP-119, the 19 kD conserved, C-terminal region of PfMSP-1, and PfF2, the conserved, Duffy-binding-like (DBL) receptor-binding domain of PfEBA-175. When administered with Montanide Adjuvant, this vaccine was found to be safe in humans. Though the vaccine demonstrated good antibody response to PfF2, majority of volunteers displayed very poor antibody response against PfMSP-119 (PLoSOne, 2015). Based on the immunogenicity results, JAIVAC-1 was not taken for further clinical development and instead ICGEB group developed a novel approach to improve the immunogenicity of PfMSP-119 through its next vaccine candidate JAIVAC-2.
JAIVAC-2 (Second generation P. falciparum vaccine candidate)
In its monovalent form JAIVAC-2 is an alhydrogel formulation of recombinant protein, MSP-Fu24 (a fusion chimera consisting of PfMSP-119 and an 11kd region of PfMSP3 (PfMSP-311). The fusion chimera contains both a T-helper (TH) epitope as well as B epitopes that are the target of antibody dependent cellular inhibition (ADCI). In its bivalent form JAIVAC-2 is an alhydrogel formulation of physical mixture of PfF2 and MSP-Fu24 protein. Presently both the formulations are undergoing acute and repeat dose toxicity studies after approval from Review Committee on Genetic Manipulation (RCGM) and Animal Ethics Committee.
Inputs from :
Dr. Viranders Chauhan, ICGEB
Dr. Chetan Chitnis, ICGEB
Dr. Kavita Singh, MVDP
Dr. Paushali Mukherjee, MVDP
Dr. TS Rao, DBT
Dr. Jyoti M Logani