Safety profile of the viral vectors of attenuated fowlpox strain FP9 and modified vaccinia virus Ankara recombinant for either of 2 preerythrocytic malaria antigens, ME-TRAP or the circumsporozoite protein, in children and adults in Kenya.
BACKGROUND
We are developing a heterologous prime-boost vaccine strategy against malaria. This approach uses sequential immunization with different vectors to deliver a common preerythrocytic malaria antigen. Preliminary evidence of efficacy and safety has been previously documented in studies from an area where malaria is nonendemic. Additional safety data from an area where malaria is endemic are now required before larger-scale studies are undertaken to determine the efficacy of this vaccine strategy in the field. Other modified vaccinia virus Ankara (MVA) recombinants and prime-boost immunizations are being developed as vaccines against human immunodeficiency virus (HIV) infection, tuberculosis, and cancer, and MVA is a candidate attenuated smallpox vaccine.


METHODS
Candidate vaccines against malaria were intradermally administered to 73 adults (7 of whom were HIV positive) and 22 children in Kenya. These vaccines used the attenuated fowlpox strain FP9 and the MVA recombinant for either of 2 preerythrocytic malaria antigens, multiple preerythrocytic-stage epitopes joined with the preerythrocytic-stage antigen TRAP (ME-TRAP) and the circumsporozoite protein (CS). Adverse events were recorded.


RESULTS
Reactogenicity was mild. MVA caused less frequent and less severe cutaneous reaction if given after FP9 priming. Half doses reduced the frequency and the severity of systemic reactogenicity, and particular vaccine lots were associated with different reactogenicities. Unexpectedly, prior immunity to the ME-TRAP antigen appeared to be protective against local reactions after immunization.


CONCLUSIONS
Where the final intention is to use MVA after FP9 priming, previous testing of MVA alone overestimates reactogenicity. These recombinant vectors appear to be safe and suitable for use in larger-scale studies of children in Africa and of HIV-positive individuals.
Kenya Medical Research Institute, Centre for Geographical Medical Research (Coast), Kilifi, Kenya.
Philip
P
Bejon
Norbert
N
Peshu
Sarah C
SC
Gilbert
Brett S
BS
Lowe
Catherine S
CS
Molyneux
John
J
Forsdyke
Trudie
T
Lang
Adrian V S
AV
Hill
Kevin
K
Marsh
D016915:AIDS Vaccines; D000328:Adult; D000953:Antigens, Protozoan / Q000276:immunology*; D002648:Child; D005587:Fowlpox virus / Q000235:genetics / Q000276:immunology*; D005822:Genetic Vectors; D006679:HIV Seropositivity / Q000276:immunology; D006801:Humans; D007630:Kenya; D008288:Malaria / Q000276:immunology* / Q000635:transmission; D015800:Protozoan Proteins / Q000276:immunology*; D012449:Safety; D014613:Vaccines, Attenuated; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology*
D016915:AIDS Vaccines; D000953:Antigens, Protozoan; D015800:Protozoan Proteins; D014613:Vaccines, Attenuated; C041595:circumsporozoite protein, Protozoan