JAIVAC-1 (project completed)

Malaria Recombinant Vaccine Candidate - PfMSP-119 and PfF2

Background

There is an urgent need to develop a vaccine to provide protection against Plasmodium falciparum malaria. An effective vaccine is likely to require the combination of multiple Plasmodium falciparum antigens. Leading candidates for development of blood-stage malaria vaccines include merozoite surface proteins such as PfMSP-1, PfMSP-2, PfMSP-4 and PfMSP-5, rhoptry proteins such as PfAMA-1, PfRAP-1 and PfRAP-2, and microneme proteins such as PfEBA-175. These proteins play important functional roles in red cell invasion by Plasmodium falciparum merozoites. The International Centre for Genetic Engineering and Biotechnology (ICGEB) has developed a recombinant combination vaccine, JAIVAC-1, based on two blood-stage Plasmodium falciparum antigens produced in E. coli. JAIVAC-1 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. Both PfMSP-119 and PfEBA- 175 play distinct yet significant functional roles in red cell invasion by Plasmodium falciparum merozoites. It is therefore inferred that antibodies directed against their functional regions may have a synergistic effect and block invasion efficiently thus providing significant protection against Plasmodium falciparum malaria.

This project is co-funded by EVI and the Indian Government.

Objectives

The overall aim of this project is to develop a bivalent malaria blood stage vaccine candidate, and to assess safety and immunogenicity in phase I clinical trials.

Major Milestones

  1. Development of methods to produce gram quantities of recombinant PfMSP-119, and recombinant PfF2, under current Good Manufacturing Practice (cGMP).
  2. Identification of the adjuvant to be used for formulation of the recombinant PfF2/PfMSP-119 combination vaccine.
  3. Development of methods to formulate recombinant PfF2/PfMSP-119 combination vaccine with selected adjuvant under cGMP.
  4. Production of recombinant PfMSP-119 and PfF2 under cGMP conditions for use in phase I safety and immunogenicity clinical trials in adults and children.
  5. The conduct of comprehensive safety and toxicology studies with recombinant PfF2/PfMSP-119 formulated with adjuvant selected for human use.
  6. The conduct of one seroprevalence study in potential investigational sites.
  7. The conduct of a phase I safety and immunogenicity clinical trial of recombinant PfF2/PfMSP-119.
  8. Combination vaccine formulated in the selected adjuvant.

Achievements

  • Technology transfer from ICGEB to Bharat Biotech Pvt. Ltd.
  • Production of three clinical batches
  • Finalisation of the Bedside Formulation
  • Approval from Drugs Controller General of India (DCGI)

A phase I clinical trial in Indian adults was initiated in May 2010. The final clinical trial report is expected by June 2013.

Publications

PLOS one, 30 April 2015, DOI: 10.1371/journal.pone.0117820