The eluted and neutralized samples were combined, diluted to 20ml with MilliQ water and subsequently concentrated to the original starting volume using centrifugal concentration tubes [Vivaspin 20, Sartorius AG, Goettingen, Germany: Code no VS2021]. 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/Significance In a longitudinal study, anti-Pfs230 and Pf48/45 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. Introduction Recent successes in eliciting transmission-reducing immune responses with malaria transmission-blocking vaccines (MTBV) in animal models , , ,  have fuelled interest in future deployment Rabbit Polyclonal to TCF7 of these vaccines as part of malaria control and elimination strategies , . Understanding the dynamics of naturally acquired transmission reducing immune responses will assist in the future deployment of MTBV in endemic populations. The transmission of malaria depends on the presence of mature sexual stage parasites, gametocytes, in the human peripheral blood. Once ingested by a mosquito taking a blood meal, gametocytes will form male microgametes and female macrogametes that after fertilization and zygote formation develop into ookinetes that penetrate the mosquito midgut wall to form an oocyst underneath the basal lamina of the midgut. Each oocyst produces thousands of sporozoites, rendering the mosquito infectious to humans. The infectiousness of gametocytes to mosquitoes depends on their density Givinostat hydrochloride , ,  and level of maturation  but also on mosquito  and human immune responses . Human transmission-reducing antibodies are ingested by Anopheline mosquitoes together with gametocytes and can interfere with zygote formation and, as a consequence, further development of parasites in the mosquito vector. MTBV are designed to induce such antibody responses to reduce the infectiousness of gametocytes to mosquitoes or even block transmission completely , , . The three most promising MTBV candidates for so far are based on the induction of antibody responses against parasite antigens Pfs230, Pfs48/45 and Pfs25 , , , , . Pfs48/45 and Pfs230 are expressed on the surface of gametes and are involved in the fertilization of macrogametocytes by microgametes ; Pfs25 is a postfertilisation antigen expressed on the surface of ookinetes , and Givinostat hydrochloride plays a role in the traversal of the mosquito midgut epithelium . The gamete surface molecules Pfs48/45 and Pfs230 are also expressed in gametocytes circulating Givinostat hydrochloride in the human blood and antibody responses against these antigens are detected in naturally exposed individuals , , . This makes it possible to study the nature and duration of sexual-stage specific immunity in naturally infected individuals . Naturally acquired sexual stage-specific antibody responses may be acquired after exposure to gametocytes  and rapidly induced as part of the initial response to infection , . In contrast to antibodies against pre-erythrocytic and blood-stage antigens , , , the prevalence of sexual-stage specific antibodies does not increase with age , . Little is known about the rate of induction or longevity of sexual-stage antibody responses and this may be important for natural boosting of any vaccine induced response. Here, we determine the acquisition, longevity and functionality of sexual stage specific antibody responses in a longitudinal study in an area of low endemicity in Tanzania. Methods Ethics permission was received from the ethical committees of the National Institute for Medical Research, the Kilimanjaro Christian Medical Centre, and the London School of Hygiene and Tropical Medicine. Written consent was obtained from all participants or their parents/guardians prior to enrolment in the study. Individuals were recruited from January 2003 till December 2004 at the health centre in Msitu wa Tembo.