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PLoS One. 2015 Apr 30;10(4):e0117820. doi: 10.1371/journal.pone.0117820. eCollection 2015.

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

Author information

1
International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India.
2
Malaria Vaccine Development Program (MVDP), New Delhi, India.
3
Diagnosearch Laboratory Services, Mumbai, India.
4
European Vaccine Initiative (EVI), Heidelberg, Germany.
5
Lotus Laboratories, Bangalore, India.
6
Bharat Biotech International Ltd. (BBIL), Hyderabad, India.

Abstract

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.

PMID:
25927360
PMCID:
PMC4415778
DOI:
10.1371/journal.pone.0117820
[Indexed for MEDLINE]
Free PMC Article

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