The dynamics of naturally acquired immune responses to Plasmodium falciparum sexual stage antigens Pfs230 & Pfs48/45 in a low endemic area in Tanzania.
BACKGROUND
Naturally acquired immune responses against sexual stages of P. falciparum can reduce the transmission of malaria from humans to mosquitoes. These antigens are candidate transmission-blocking vaccines but little is known about the acquisition of sexual stage immunity after exposure to gametocytes, or their longevity and functionality. We conducted a longitudinal study on functional sexual stage immune responses.


RESULTS
Parasitaemic individuals (n = 116) were recruited at a health centre in Lower Moshi, Tanzania. Patients presented with gametocytes (n = 16), developed circulating gametocytes by day 7 (n = 69) or between day 7 and 14 (n = 10) after treatment or did not develop gametocytes (n = 21). Serum samples were collected on the first day of gametocytaemia and 28 and 84 days post-enrolment (or d7, 28, 84 after enrolment from gametocyte-negative individuals). Antibody responses to sexual stage antigens Pfs230 and Pfs48/45 were detected in 20.7% (72/348) and 15.2% (53/348) of the samples, respectively, and were less prevalent than antibodies against asexual stage antigens MSP-1(19) (48.1%; 137/285) and AMA-1 (52.4%; 129/246)(p<0.001). The prevalence of anti-Pfs230 (p = 0.026) and anti-Pfs48/45 antibodies (p = 0.017) increased with longer duration of gametocyte exposure and had an estimated half-life of approximately 3 months. Membrane feeding experiments demonstrated a strong association between the prevalence and concentration of Pfs230 and Pfs48/45 antibodies and transmission reducing activity (TRA, p<0.01).


CONCLUSIONS
In a longitudinal study, anti-Pfs230 and Pfs48/45 antibodies developed rapidly after exposure to gametocytes and were strongly associated with transmission-reducing activity. Our data indicate that the extent of antigen exposure is important in eliciting functional transmission-reducing immune responses.
Department of Immunology & Infection, Faculty of Infectious & Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom.
Teun
T
Bousema
Will
W
Roeffen
Hinta
H
Meijerink
Harry
H
Mwerinde
Steve
S
Mwakalinga
Geert-Jan
GJ
van Gemert
Marga
M
van de Vegte-Bolmer
Frank
F
Mosha
Geoffrey
G
Targett
Eleanor M
EM
Riley
Robert
R
Sauerwein
Chris
C
Drakeley
D000293:Adolescent; D000328:Adult; D000913:Antibodies, Protozoan / Q000097:blood / Q000276:immunology; D000953:Antigens, Protozoan / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D019353:Endemic Diseases; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D016778:Malaria, Falciparum / Q000453:epidemiology / Q000276:immunology*; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology*; D008875:Middle Aged; D010963:Plasmodium falciparum / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology*; D013636:Tanzania / Q000453:epidemiology; D013997:Time Factors; D055815:Young Adult
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D008562:Membrane Glycoproteins; C430263:Pfs230 antigen, Plasmodium falciparum; D015800:Protozoan Proteins; C084847:pfs48-45 protein, Plasmodium falciparum