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


METHODS
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.


CONCLUSIONS
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.


BACKGROUND
Clinical Trial Registry, India CTRI/2010/091/000301.
International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India.
Chetan E
CE
Chitnis
International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India.
Paushali
P
Mukherjee
Malaria Vaccine Development Program (MVDP), New Delhi, India.
Shantanu
S
Mehta
International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India.
Syed Shams
SS
Yazdani
International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India.
Shikha
S
Dhawan
International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India.
Ahmad Rushdi
AR
Shakri
Rukmini
R
Bhardwaj
International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India.
Rukmini
R
Bharadwaj
International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India.
Puneet Kumar
PK
Gupta
International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India.
Dhiraj
D
Hans
International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India.
Suman
S
Mazumdar
International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India.
Bijender
B
Singh
International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India.
Sanjeev
S
Kumar
Malaria Vaccine Development Program (MVDP), New Delhi, India.
Gaurav
G
Pandey
Diagnosearch Laboratory Services, Mumbai, India.
Varsha
V
Parulekar
European Vaccine Initiative (EVI), Heidelberg, Germany.
Nathalie
N
Imbault
Lotus Laboratories, Bangalore, India.
Preethi
P
Shivyogi
Lotus Laboratories, Bangalore, India.
Girish
G
Godbole
Bharat Biotech International Ltd. (BBIL), Hyderabad, India.
Krishna
K
Mohan
European Vaccine Initiative (EVI), Heidelberg, Germany.
Odile
O
Leroy
Malaria Vaccine Development Program (MVDP), New Delhi, India.
Kavita
K
Singh
International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India.
Virander S
VS
Chauhan
D000293:Adolescent; D000328:Adult; D000913:Antibodies, Protozoan / Q000276:immunology; D000953:Antigens, Protozoan / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D017325:Hepatitis B Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007194:India; D017780:Malaria Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D016778:Malaria, Falciparum / Q000276:immunology / Q000517:prevention & control*; D008297:Male; D008353:Mannitol / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D020066:Merozoite Surface Protein 1 / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D008875:Middle Aged; D009829:Oleic Acids / Q000008:administration & dosage / Q000009:adverse effects; D010963:Plasmodium falciparum / Q000276:immunology*; D015800:Protozoan Proteins / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D017325:Hepatitis B Vaccines; D007074:Immunoglobulin G; D017780:Malaria Vaccines; D020066:Merozoite Surface Protein 1; D009829:Oleic Acids; D015800:Protozoan Proteins; C065668:erythrocyte-binding antigen 175, Plasmodium; C001681:mannide monooleate; D008353:Mannitol