Immunogenicity and protective efficacy of Escherichia coli expressed Plasmodium falciparum merozoite surface protein-1(42) using human compatible adjuvants

The C-terminal 42-kDa fragment of the merozoite surface protein-1 of Plasmodium falciparum (PfMSP-1(42)) was expressed as a recombinant protein in Escherichia coli and purified to near homogeneity. We tested the immunogenicity of recombinant PfMSP-1(42) in three clinically acceptable adjuvants (Montanide ISA 720, alum and MF59) in mice and in rabbits. High antibody responses were obtained with two adjuvant formulations with IgGl being the predominant immunoglobulin isotype. Significant T-cell proliferation responses were also observed. Competitive enzyme linked immunosorbant assay (ELISA) showed the presence of both invasion and processing inhibitory antibodies in sera obtained from the immunized rabbits. Passive immunizations of mice with anti-PfMSP-1(42) IgG purified from the rabbit-sera were found to be protective against a parasite challenge with P. berghei/P. falciparum chimeric line (Pb-PfM19) that expresses Plasmodium falciparum MSP-1(19). These findings may be useful for the development of a malaria vaccine based on Plasmodium falciparum MSP-1(42).     

Development of a candidate DNA/MVA HIV-1 subtype C vaccine for India

Development of a vaccine against human immunodeficiency virus type-1 (HIV-1) is the mainstay for controlling the AIDS pandemic. An ideal HIV vaccine should induce neutralizing antibodies, CD4+ helper T cells, and CD8+ cytotoxic T cells. While the induction of broadly neutralizing antibodies remains a highly challenging goal, there are a number of technologies capable of inducing potent cell-mediated responses in animal models, which are now starting to be tested in humans. Naked DNA immunization is one of them. The present study focuses on the stimulation cell-mediated and humoral immune responses by recombinant DNA-MVA vaccines, the areas where this technology might assist either alone or as a part of more complex vaccine formulations in the HIV vaccine development. Candidate recombinant DNA-MVA vaccine formulations expressing the human immunodeficiency virus-1 env and gagprotease genes from HIV-1 Indian subtype C were constructed and characterized. A high level of expression of the respective recombinant MVA (rMVA) constructs was demonstrated in BHK-21 cells followed by the robust humoral as well as cell mediated immune (CMI) responses in terms of magnitude and breadth. The response to a single inoculation of the rDNA vaccine was boosted efficiently by rMVA in BALB/c mice. This is the first reported candidate HIV-1 DNA/MVA vaccine employing the Indian subtype C sequences and constitutes a part of a vaccine scheduled to enter a preclinical non-human primate evaluation in India.