© 2004 Blackwell Publishing Ltd 159 Parasite Immunology , 2004, 26, 159–165 Blackwell Publishing, Ltd. ORIGINAL ARTICLE Immunity to P. falciparumgametocytes in Gambian children Parasite infectivity and immunity to Plasmodium falciparum gametocytes in Gambian children C. J. DRAKELEY, 1,2,3 W. ELING, 3 K. TEELEN, 3 J. T. BOUSEMA, 3 R. SAUERWEIN, 3 B. M. GREENWOOD 1,2 & G. A. T. TARGETT 1 1 Department of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, Keppel St., London WC1E 7HT, UK, 2 Medical Research Council Laboratories, Fajara, PO Box 273, The Gambia and 3 Department of Medical Microbiology, University Medical Centre Nijmegen, P.O. Box 9101, 6500 HB, Nijmegen, the Netherlands SUMMARY Immunity to the sexual stages of Plasmodium falciparum can be induced during natural infections. Characterization of this immunity may facilitate the design of a transmission-blocking vaccine (TBV). This study aimed to assess the prevalence and serological correlates of functional transmission-blocking immunity in Gambian children (aged 1–4 years old) who were P. falciparum gametocyte carriers. Serological assays showed 100% response to fixed, whole parasites but only 42% to live gametes. Responses to the antigens Pfs230 and Pfs48/45 were 54·1% and 37·3%, respectively, in an IgG1 ELISA. 14/55 sera were capable of reducing the infectivity of laboratory isolate NF54 in a standard membrane-feeding assay (SMFA). This activity was strongly correlated with IgG1 responses to Pfs48/ 45 ( r = 0·49, P < 0·001) and to a serological reaction with epitopes of the same molecule (r = 0·38, P = 0·003). A weaker correlation was observed with IgG1 to Pfs230 (r = 0·29, P = 0·03). In direct membrane feeding assays (DMFA) with autologous isolates, sera from 4/29 children showed transmission- blocking activity. There was no correlation with serological assays and the DMFA or between the SMFA and DMFA. This may be caused by variation in sexual stage antigens and/or alternative modes of transmission-blocking immunity, both of which have implications for vaccine implementation. Keywords gametes, gametocytes, malaria, P. falciparum, Pfs230, Pfs48/45, transmission-blocking immunity INTRODUCTION The continuation of the malaria life cycle is critically depen- dent on the transmission of the sexual stages of the parasite from the mammalian host to the Anopheles mosquito vector. Vaccine-induced immunity to these sexual stages has the potential to reduce malaria transmission (1). Characteriza- tion of effective immunity against the sexual stages developed through natural exposure to P. falciparum and the identifica- tion of the targets of this immune response will help with the development of a transmission-blocking vaccine (TBV ). Transmission blocking immunity (TBI) has been demon- strated in both experimental (2) and natural situations (3–5). In the case of P. falciparum, antibodies to the principal pre-fertilization gametocyte antigens, Pfs230 and Pfs48/45, have been documented in sera from individuals exposed to various intensities of transmission (3,6 –9). Importantly, the transmission-blocking ability of immune human sera has been correlated with the presence of antibodies to both of these antigens (3,8,10). However, there is little consistency in the pattern of this response. Thus, whilst a good correlation between transmission-blocking and antibodies to Pfs230 was documented for Gambian (10) and Papua New Guinean (PNG) sera (3), this was not seen with Cameroonian blocking sera, which reacted more strongly with Pfs48/45 (8). In contrast, the transmission-blocking ability of Sri-Lankan sera corre- lated with antibodies to neither Pfs230 nor Pfs48/45 (11). The sexual stages of Plasmodium falciparum are most pre- valent in children, who also support the highest densities of asexual and sexual parasites. We have examined the immune recognition of the sexual stages of P. falciparum by sera from young Gambian gametocyte carriers. Responses to whole parasite and native and synthetic antigens were measured and compared with natural and experimental parasite infec- tivity. The data are discussed with reference to the predictive ability of sero-reactivity for transmission-blocking activity, the comparison of natural vs. experimental infectivity and the epidemiology of sexual stage immunity. Correspondence: C. J. Drakeley, Joint Malaria Programme, Box 2228, Moshi, Tanzania (e-mail: chris.drakeley@lshtm.ac.uk). Accepted for publication: 21 June 2004