Journal Article

Phase I Clinical Trial of a Recombinant Blood Stage Vaccine Candidate for Plasmodium falciparum Malaria Based on MSP1 and EBA175

Mehta, Shantanu, Singh, Bijender, Mazumdar, Suman, Kumar, Sanjeev, Mohan, Krishna, Shivyogi, Preethi, Dhawan, Shikha, Leroy, Odile, Shakri, Ahmad Rushdi, Gupta, Puneet Kumar, Hans, Dhiraj, Chitnis, Chetan E., Mukherjee, Paushali, Singh, Kavita, Pandey, Gaurav, Chauhan, Virander S., Imbault, Nathalie, Yazdani, Syed Shams, Parulekar, Varsha, Godbole, Girish, Bharadwaj, Rukmini

2015

Overview

A phase I randomised, controlled, single blind, dose escalation trial was conducted to evaluate safety and immunogenicity of JAIVAC-1, a recombinant blood stage vaccine candidate against Plasmodium falciparum malaria, composed of a physical mixture of two recombinant proteins, PfMSP-1(19), the 19 kD conserved, C-terminal region of PfMSP-1 and PfF2 the receptor-binding F2 domain of EBA175. Healthy malaria naïve Indian male subjects aged 18-45 years were recruited from the volunteer database of study site. Fifteen subjects in each cohort, randomised in a ratio of 2:1 and meeting the protocol specific eligibility criteria, were vaccinated either with three doses (10 μg, 25 μg and 50 μg of each antigen) of JAIVAC-1 formulated with adjuvant Montanide ISA 720 or with standard dosage of Hepatitis B vaccine. Each subject received the assigned vaccine in the deltoid muscle of the upper arms on Day 0, Day 28 and Day 180. JAIVAC-1 was well tolerated and no serious adverse event was observed. All JAIVAC-1 subjects sero-converted for PfF2 but elicited poor immune response to PfMSP-1(19). Dose-response relationship was observed between vaccine dose of PfF2 and antibody response. The antibodies against PfF2 were predominantly of IgG1 and IgG3 isotype. Sera from JAIVAC-1 subjects reacted with late schizonts in a punctate pattern in immunofluorescence assays. Purified IgG from JAIVAC-1 sera displayed significant growth inhibitory activity against Plasmodium falciparum CAMP strain. Antigen PfF2 should be retained as a component of a recombinant malaria vaccine but PfMSP-1(19) construct needs to be optimised to improve its immunogenicity. Clinical Trial Registry, India CTRI/2010/091/000301.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adolescent / Adult / Antibodies / Antibodies, Protozoan - immunology / Antibody response / Antigens, Protozoan - administration & dosage / Antigens, Protozoan - adverse effects / Antigens, Protozoan - immunology / Blood / Clinical trials / Dose-response relationship / Dose-Response Relationship, Drug / Dose-Response Relationship, Immunologic / Female / Hepatitis / Hepatitis B / Hepatitis B vaccines / Hepatitis B Vaccines - administration & dosage / Hepatitis B Vaccines - adverse effects / Hepatitis B Vaccines - immunology / Hepatitis B virus / Humans / Immune response / Immune system / Immunofluorescence / Immunogenicity / Immunoglobulin G / Immunoglobulin G - immunology / India / Malaria / Malaria vaccines / Malaria Vaccines - administration & dosage / Malaria Vaccines - adverse effects / Malaria Vaccines - immunology / Malaria, Falciparum - immunology / Malaria, Falciparum - prevention & control / Male / Mannitol - administration & dosage / Mannitol - adverse effects / Mannitol - analogs & derivatives / Merozoite Surface Protein 1 - administration & dosage / Merozoite Surface Protein 1 - adverse effects / Merozoite Surface Protein 1 - immunology / Middle Aged / Muscles / Oleic Acids - administration & dosage / Oleic Acids - adverse effects / Plasmodium / Plasmodium falciparum / Plasmodium falciparum - immunology / Proteins / Protozoan Proteins - administration & dosage / Protozoan Proteins - adverse effects / Protozoan Proteins - immunology / Randomization / Recombinant proteins / Schizonts / Vaccination / Vaccines / Vector-borne diseases