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© François Rodhain
Plasmodium malariae (un des quatre hématozoaires qui parasitent l'homme), agent du paludisme, dans un frottis de sang humain. Stade trophozoïte. Coloration de May-Grünwald Giemsa.
Publication : PloS one

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

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in PloS one - 30 Apr 2015

Chitnis CE, Mukherjee P, Mehta S, Yazdani SS, Dhawan S, Shakri AR, Bharadwaj R, Gupta PK, Hans D, Mazumdar S, Singh B, Kumar S, Pandey G, Parulekar V, Imbault N, Shivyogi P, Godbole G, Mohan K, Leroy O, Singh K, Chauhan VS

Link to Pubmed [PMID] – 25927360

PLoS ONE 2015;10(4):e0117820

BACKGROUND: 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.

METHOD: 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.

RESULTS: 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.

CONCLUSION: 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.

TRIAL REGISTRATION: Clinical Trial Registry, India CTRI/2010/091/000301.