By H. J. Bensted, W. Bulloch, L. Dudgeon, A. G. Gardner, E. D. W. Greig, D. Harvey, W. F. Harvey, T. J. Mackie, R. A. O'Brien, H. M. Perry, H. Scutze, P. Bruce White, W. J. Wilson. London, 1929. His Majesty's Stationery Office. Pp. 1–482
by A. Trevor Willis, M.D., B.S. (Melb.), Ph.D. (Leeds), M.C.Path., M.C.P.A., Reader in Microbiology, Monash University, formerly Lecturer in Bacteriology, University of Leeds. xiv + 234 pages, illustrated, second edition. Butterworth Inc., Washington. 1965. $8.50
Tropical Medicine Unit and Preclinical Research Departments, F. Hoffmann-La Roche & Co., Ltd., University Children's Hospital, Queensland Institute of Medical Research, Walter and Eliza Hall Institute of Medical Research, Biotech Australia Pty. Ltd., Commonwealth Serum Laboratories Ltd., Institute for Medical Informatics and Biostatistics, Basel, Switzerland
This study was part of a larger program to develop a vaccine effective against Plasmodium falciparum infection caused by sporozoites and clinical malaria caused by asexual blood stages. In a phase 1 study of safety and immunogenicity, two recombinant proteins (Ro 46–2717, a circumsporozoite [CS] protein) construct with a molecular mass of 35 kD, and Ro 46-2924, a merozoite surface antigen [MSA-2] construct with a molecular mass of 25 kD) adsorbed onto alum were injected in two low (20 µg) or two high (100 µg) doses in the right and left deltoid muscles of 33 healthy Swiss volunteers; six other volunteers received a placebo (alum alone). Twenty-six participants reported 51 immunization-related adverse events, mainly pain at the injection site. Mean antibody titers to CS protein and MSA-2 in an indirect immunofluorescence assay peaked four weeks after the second immunization without evidence of boosting (i.e., sharp increase in titer). By that time, 56% and 31% of the vaccinees seroconverted to CS protein and MSA-2, respectively, with the increase in MSA-2 titer being weaker than that for the CS protein. After a third immunization, five vaccinees volunteered to be challenged by three or four infective bites of Anopheles stephensi. Prepatent and incubation periods in all five were comparable with unvaccinated historic controls challenged under similar conditions, and all had symptoms of clinical falciparum malaria. We conclude that the vaccine components were safe and immunogenic but there was no evidence that this immunization regimen with the CS protein plus MSA-2 component was able to prevent infection. Because the protocol required treatment in ≤ 24 hr after detection of parasitemia, the contribution of MSA-2 as an anti-disease vaccine candidate will be further evaluated in a field trial.