Rapid Onset of Transmission-Reducing Antibodies in Javanese Migrants Exposed to Malaria in Papua, Indonesia

Abstract

Transmission of Plasmodium falciparum malaria is initiated by sexual stages in the mosquito. Anti-Pfs48/45 and anti-Pfs230 sexual stage antibodies that are ingested together with parasites can reduce parasite development and subsequently malaria transmission. Acquisition of sexual stage immunity was studied in a cohort of 102 non-immune Javanese individuals migrating to hyperendemic Papua Indonesia. Seroprevalence of antibodies against Pfs48/45 and Pfs230 and functional transmission-reducing activity (TRA) were measured upon arrival and at 6, 12, and 24 months. Asexual parasitemia and gametocytemia were assessed every two weeks. The TRA and seroreactivity increased with the number of P. falciparum infections. The longitudinally sustained association between TRA and antibodies against Pfs48/45 (odds ratio [OR] = 3.74, 95% confidence interval [CI] = 1.51-9.29) and Pfs230 (OR = 3.72, 95% CI = 1.36-10.17) suggests that functional transmission reducing immunity is acquired after limited exposure to infection.

Naturally Acquired Immune Responses to Plasmodium falciparum Sexual Stage Antigens Pfs48/45 and Pfs230 in an Area of Seasonal Transmission

“…As in previous studies (6,9,18,23,26,43,44), we found evidence for naturally acquired immunity against P. falciparum sexual stages. Overall, 22 to 28% of our samples were positive for sexual stage-specific antibodies, while 54 to 65% were positive for preerythrocyte-and asexual blood stage-specific antibodies.…”

“…However, the seasonality of sexual stage-specific immune responses (28) has been rarely studied, making any comparison difficult. The importance of recent exposure to infection for the acquisition of sexual stage-specific immunity has been reported from previous studies in which the prevalence of anti-Pfs48/45 and anti-Pfs230 antibodies increased in migrants from an area of nonendemicity to an area of endemicity (9) and where functional transmission-reducing immunity was shown to increase during the transmission season (12). We did not determine functional transmission-reducing immune responses in the current data set.…”

“…Spearman's rank correlation test was used to assess association between antibody levels of tested antigens. The association between Pfs230 and Pfs48/45 antibody responses and functional transmission-reducing activity (TRA) in the standard membrane feeding assay (SMFA) in previous studies (9,11,18) was presented after categorization of TRA as Ͼ50% and Ͼ90% reduction (9,11,18) and calculating odds ratios (OR) with 95% confidence intervals (95% CI). The level of significance was set at a two-tailed P value of Ͻ0.05.…”

“…The volume of plasma that remained from this study was insufficient to study functional transmission-reducing activity in the standard membrane feeding assay (SMFA). To aid interpretation of the current results, paired ELISA-SMFA data from three studies (9,11,18) were combined and are presented in Table 4. Sexual stage antibody responses were determined using exactly the same ELISA methodology as used in the current study.…”

N-Terminal Prodomain of Pfs230 Synthesized Using a Cell-Free System Is Sufficient To Induce Complement-Dependent Malaria Transmission-Blocking Activity

“…(3) reported that the antibody response to Pfs230 is boosted by exposure to gametocytes. To date, most of those studies used the sandwich ELISA method using anti-Pfs230 MAbs in combination with cultured P. falciparum gametocyte crude lysates (2). In the case of TBV application in future field trials, seroepidemiological surveillance of such naturally existing transmission-reducing immunity seems to be essential; however, the availability of crude parasite antigen for such a large-scale study is one of the hurdles to be overcome.…”