Transmission-blocking activity induced by malaria vaccine candidates Pfs25/Pvs25 is a direct and predictable function of antibody titer.
BACKGROUND
Mosquito stage malaria vaccines are designed to induce an immune response in the human host that will block the parasite's growth in the mosquito and consequently block transmission of the parasite. A mosquito membrane-feeding assay (MFA) is used to test transmission-blocking activity (TBA), but in this technique cannot accommodate many samples. A clear understanding of the relationship between antibody levels and TBA may allow ELISA determinations to be used to predict TBA and assist in planning vaccine development.


METHODS
Rabbit anti-Pfs25 sera and monkey anti-Pvs25 sera were generated and the antibody titers were determined by a standardized ELISA. The biological activity of the same sera was tested by MFA using Plasmodium gametocytes (cultured Plasmodium falciparum or Plasmodium vivax from malaria patients) and Anopheles mosquitoes.


RESULTS
Anti-Pfs25 and anti-Pvs25 sera showed that ELISA antibody units correlate with the percent reduction in the oocyst density per mosquito (Spearman Rank correlations: 0.934 and 0.616, respectively), and fit a hyperbolic curve when percent reduction in oocyst density is plotted against antibody units of the tested sample. Antibody levels also correlated with the number of mosquitoes that failed to become infected, and this proportion can be calculated from the reduction in oocyst numbers and the distribution of oocysts per infected mosquito in control group.


CONCLUSIONS
ELISA data may be used as a surrogate for the MFA to evaluate transmission-blocking vaccine efficacy. This will facilitate the evaluation of transmission-blocking vaccines and implementation of this malaria control strategy.
Miura
Kazutoyo
K
Malaria Vaccine Development Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, USA. kmiura@niaid.nih.gov
Keister
David B
DB
Muratova
Olga V
OV
Sattabongkot
Jetsumon
J
Long
Carole A
CA
Saul
Allan
A
D000818:Animals; D000852:Anopheles / Q000469:parasitology / Q000502:physiology; D000913:Antibodies, Protozoan / Q000097:blood* / Q000502:physiology*; D000953:Antigens, Protozoan / Q000276:immunology*; D000954:Antigens, Surface / Q000276:immunology*; D002452:Cell Count; D009033:Culicidae / Q000469:parasitology / Q000502:physiology; D018562:Disease Transmission, Infectious / Q000517:prevention & control; D005260:Female; D006801:Humans; D007114:Immunization; D007115:Immunization Schedule; D007273:Injections, Intramuscular; D008253:Macaca mulatta; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000276:immunology*; D016778:Malaria, Falciparum / Q000097:blood* / Q000517:prevention & control / Q000635:transmission; D016780:Malaria, Vivax / Q000097:blood* / Q000517:prevention & control / Q000635:transmission; D008297:Male; D009865:Oocytes / Q000166:cytology; D010963:Plasmodium falciparum / Q000276:immunology*; D010966:Plasmodium vivax / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology*; D011817:Rabbits; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D000954:Antigens, Surface; D017780:Malaria Vaccines; C071284:Pfs25 protein, Plasmodium falciparum; D015800:Protozoan Proteins; C121473:Pvs25 protein, P vivax; D014614:Vaccines, Synthetic