The Dynamics of Naturally Acquired Immune Responses to Plasmodium falciparum Sexual Stage Antigens Pfs230 & Pfs48/45 in a Low Endemic Area in Tanzania.


Bousema, T; Roeffen, W; Meijerink, H; Mwerinde, H; Mwakalinga, S; van Gemert, GJ; van de Vegte-Bolmer, M; Mosha, F; Targett, G; Riley, EM; Sauerwein, R; Drakeley, C; (2010) The Dynamics of Naturally Acquired Immune Responses to Plasmodium falciparum Sexual Stage Antigens Pfs230 & Pfs48/45 in a Low Endemic Area in Tanzania. PLoS One, 5 (11). e14114. ISSN 1932-6203 DOI: https://doi.org/10.1371/journal.pone.0014114

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Abstract

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. METHODOLOGY/PRINCIPAL FINDINGS: 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/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.

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Immunology and Infection
Research Centre: Malaria Centre
PubMed ID: 21124765
Web of Science ID: 284686500006
URI: http://researchonline.lshtm.ac.uk/id/eprint/1970

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