Naturally acquired immunity to sexual stageP. falciparumparasites

Abstract

Gametocytes are the specialized form of Plasmodium parasites that are responsible for human-to-mosquito transmission of malaria. Transmission of gametocytes is highly effective, but represents a biomass bottleneck for the parasite that has stimulated interest in strategies targeting the transmission stages separately from those responsible for clinical disease. Studying targets of naturally acquired immunity against transmission-stage parasites may reveal opportunities for novel transmission reducing interventions, particularly the development of a transmission blocking vaccine (TBV). In this review, we summarize the current knowledge on immunity against the transmission stages of Plasmodium. This includes immune responses against epitopes on the gametocyte-infected erythrocyte surface during gametocyte development, as well as epitopes present upon gametocyte activation in the mosquito midgut. We present an analysis of historical data on transmission reducing immunity (TRI), as analysed in mosquito feeding assays, and its correlation with natural recognition of sexual stage specific proteins Pfs48/45 and Pfs230. Although high antibody titres towards either one of these proteins is associated with TRI, the presence of additional, novel targets is anticipated. In conclusion, the identification of novel gametocyte-specific targets of naturally acquired immunity against different gametocyte stages could aid in the development of potential TBV targets and ultimately an effective transmission blocking approach.

Prevalence of Plasmodium falciparum transmission reducing immunity among primary school children in a malaria moderate transmission region in Zimbabwe

“…However, when analyzed by nested PCR analysis, it was astonishing to observe widespread prevalence of apparently asymptomatic malaria in this population. Generally, it is believed that such asymptomatic status is achieved in adults who have had repeat exposure to malaria resulting in induction of partially protective clinical immunity (Achtman et al, 2005; Baird, 1998; Langhorne et al, 2008; STONE et al, 2016). It was rather unexpected to find as much as 66% PCR positivity in the participants for two reasons.…”

“…First the perception in the area is that the malaria is not a serious risk factor in this population (malaria incidence 46/1000, Ministry of Health, Zimbabwe). Second, all the study participants were school age children between 6–16 years of age, showing unlikely development of protective immunity which requires repeated exposures over a long time period (Baird, 1998; STONE et al, 2016). Clearly, similar PCR analysis needs to be established in other parts of Zimbabwe and other areas pursuing malaria elimination goal to ensure sufficient treatment coverage and complete absence of asymptomatic malaria (Bousema et al, 2016; Schneider et al, 2006; Shekalaghe et al, 2007a).…”

“…Although some of the plasma samples showed blocking to an extent that was commensurate with the anti-Pfs48/45 antibody determinations, others though with higher antibody reactivity were not as effective in blocking. Differences in the recognition of epitopes and in the presence of antibodies against other sexual stage specific target antigens may contribute to these differences (Graves et al, 1988; Skinner et al, 2015; STONE et al, 2016). Additional studies are needed to determination a detailed correlation between antibody titers, antigen specificity and transmission blocking activity.…”

“…Gametocytes are crucial for transmission of malaria from an infected person to mosquito vector. Upon ingestion, gametocytes undergo gametogenesis into male and female gametes which undergo fertilization and further sporogonic development (Dantzler et al, 2015; Nilsson et al, 2015; STONE et al, 2016). …”

Naturally acquired immunity to malaria

“…The decision of the parasite to undergo gametocytogenesis enables transmission to the mosquito vector and subsequently, to other human hosts. Stone et al (2015) provide a thorough overview of evidence for natural immune responses to both the developing gametocyte inside human erythrocytes and activated gametocyte forms within the mosquito midgut. These immune responses, thought to include both humoral and cellular responses, reduce transmission by acting directly on intraerythrocytic gametocytes.…”