Multi Vaccine Development Program. Not For Profit Research Society

P.falciparum, JAIVAC-1

Candidate Malaria Vaccine: JAIVAC-1 Vaccine (PfMSP-119 and PfF2) formulated with Adjuvant Montanide ISA 720.

Route of administration: Intramuscular

Clinical Development Phase: Phase I (First-in-man) completed, Published PloS One 2015

Objectives: The overall objective of the project was to develop a recombinant bivalent erythrocytic stage malaria vaccine. Through the conduct of the Phase I trial, the aim was to evaluate the safety and immunogenicity of the vaccine candidate in healthy Indian adult male subjects.

Current Status: This first-in-man randomised, controlled, single blind clinical trial in healthy Indian male subjects aged between 18 to 45 years was completed in 2013 (CTRI/2010/091/000301). This was a dose-escalating study and involved testing of three (3) different dosages of JAIVAC-1 malaria vaccine (PfMSP-119 and PfF2) formulated with Montanide ISA 720 as adjuvant. The results of this study have been reported in PLoS One (2015).

Biological Rationale: Malaria is a serious tropical infectious disease which accounts for a large number of deaths in children under the age of 5 years, especially in sub-Saharan Africa. It is transmitted by the bite of infectious female Anopheline mosquito. There are four species of the protozoan Plasmodia that cause human disease namely, Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae and Plasmodium ovale.

With the emergence of drug resistant strains of Plasmodia and insecticide resistant mosquitoes, there is an urgent need to develop other effective tools that will help in achieving the target of malaria eradication. An effective malaria vaccine is likely to contribute towards the repertoire of the available tools to combat malaria. Further, since the majority of deaths caused by malaria are due to the falciparum species, the efforts of the malaria vaccine community have been largely focused on developing a vaccine against Plasmodium falciparum malaria.

Malaria vaccine approaches can be broadly grouped as pre-erythrocytic, blood stage and transmission blocking. There is a strong rational for developing an erythrocytic vaccine since the blood stage of the malaria parasite is primarily responsible for the clinical symptoms experienced by the host. The underlying principle towards developing an erythrocytic vaccine is that the antibodies generated after administering the vaccine are expected to prevent the merozoites liberated from the liver from invading the red blood cells in circulation. This is expected to prevent lysis of the erythrocytes thereby provide protection against clinical disease.

Most of the earlier efforts in developing a malaria vaccine have been focused on single antigens; this holds true for the blood stage vaccine candidates evaluated. The results of the early development studies with the blood stage candidates have been disappointing and none of these candidates have been able to progress beyond Phase II field trials. It is therefore expected that an effective blood stage malaria vaccine is likely to require the combination of multiple Plasmodium falciparum antigens.

At present, the leading blood stage candidates under development are those which are located either on the merozoite surface or contained within the apical organelles of merozoites. The major erythrocytic vaccine candidates are: PfMSP-1, PfMSP-2, PfMSP-3, PfAMA-1, PfEBA-175 and SERA-5. All of these proteins play important functional roles in red cell invasion and multiplication within the erythrocytes of Plasmodium falciparum merozoites.

JAIVAC-1 is a recombinant vaccine composed of two blood-stage P.falciparum antigens. The vaccine was developed by scientists at the International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi. The final vaccine formulation was 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. JAIVAC-1 is predicted to prevent malaria by targeting these two key parasite proteins that play important functional roles in invasion. This antigen combination is expected to provide an effective strategy to block red cell invasion, reduce blood-stage growth and prevent malaria.The phase I clinical trial in Indian adults was initiated in May 2010 and completed in 2013. The immunogenicity analysis of Phase I clinical trial serum samples of healthy adult male volunteers showed good antibody response to PfF2, as measured by Enzyme Linked Immunosorbent Assay (ELISA). However, majority of volunteers displayed very poor antibody response against PfMSP-119 (PLoS One. 2015*). Based on these results,it was concluded that PfF2 should be retained as a component of a recombinant malaria vaccine but PfMSP-119 construct needs to be optimised to improve its immunogenicity. An optimized version of this vaccine candidate (named JAIVAC-2) is being developed.*Chitnis CE, Mukherjee P, Mehta S, Yazdani SS, Dhawan S, Shakri AR, et al. (2015) Phase I Clinical Trial of a Recombinant Blood Stage Vaccine Candidate for Plasmodium falciparum Malaria Based on MSP1 and EBA175. PLoS ONE 10(4): e0117820.

Key Organizations

Organization Role
DBT, Government of India Co-Funded the project with EVI
International Centre for Genetic Engineering and Biotechnology, New-Delhi, India Discovered the candidate vaccine and also co-sponsors for the project with EVI
European Vaccine Initiative, Heidelberg, Germany Co-Funded the project with DBT and also co-sponsors for the project with ICGEB
Bharat Biotech International Limited, Hyderabad, India cGMP manufacture of JAIVAC-1
Seppic, France Manufacturer of Adjuvant Montanide ISA 720
Malaria Vaccine Development Program, New Delhi, India Sponsor's representative for overall management of the Phase I clinical trial
Diagnosearch Life Sciences Private Limited, Mumbai, India Contract Research Organization for clinical trial and data management of Phase I trial
Lotus Laboratories Private Limited, Bengaluru, India Study site for the Phase I trial