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

Abstract

Acquisition of immunity to Plasmodium falciparum sexual stages is a key determinant for reducing humanmosquito transmission by preventing the fertilization and the development of the parasite in the mosquito midgut. Naturally acquired immunity against sexual stages may therefore form the basis for the development of transmission-blocking vaccines, but studies conducted to date offer little in the way of consistent findings. Here, we describe the acquisition of antigametocyte immune responses in malaria-exposed individuals in Burkina Faso. A total of 719 blood samples were collected in a series of three cross-sectional surveys at the start, peak, and end of the wet season. The seroprevalence of antibodies with specificity for the sexual stage antigens Pfs48/45 and Pfs230 was 2-fold lower (22 to 28%) than that for an asexual blood stage antigen glutamate-rich protein (GLURP) (65%) or for the preerythrocytic stage antigen circumsporozoite protein (CSP) (54%). The youngest children responded at frequencies similar to those for all four antigens but, in contrast with the immune responses to GLURP and CSP that increased with age independently of season and area of residence, there was no evidence for a clear age dependence of responses to Pfs48/45 and Pfs230. Anti-Pfs230 antibodies were most prevalent at the peak of the wet season (P < 0.001). Our findings suggest that naturally acquired immunity against Pfs48/45 and Pfs230 is a function of recent exposure rather than of cumulative exposure to gametocytes.

The s48/45 six-cysteine proteins: mediators of interaction throughout the Plasmodium life cycle

“…To date, only the molecular structures for Pf12 and Pf41 have been solved and, as anticipated, each domain of these proteins superimposes well with the original s48/45 structure (Arredondo et al, 2012; Tonkin et al, 2013; Parker et al, 2015). However, outside the main core of the domains, interesting flexible features are observed as seen by NMR in the C-terminus of Pf12, which might also be the case for an insertion domain in Pf41 that is necessary for binding to Pf12 (Arredondo et al, 2012; Parker et al, 2015).…”

“…However, outside the main core of the domains, interesting flexible features are observed as seen by NMR in the C-terminus of Pf12, which might also be the case for an insertion domain in Pf41 that is necessary for binding to Pf12 (Arredondo et al, 2012; Parker et al, 2015). Unfortunately, no function has been assigned to Pf12 and Pf41.…”

High and Heterogeneous Prevalence of Asymptomatic and Sub-microscopic Malaria Infections on Islands in Lake Victoria, Kenya

“…found evidence that within a narrow age band—6 months to 10 years—there may be a positive association between age and the likelihood of transmission28. This has been associated with naturally acquired human immune responses against gametocyte antigens that may reduce or prevent the transmission of malaria parasites to mosquitoes2930 and may be highly prevalent in young age groups29. In contrast with immune responses to the asexual stages of P. falciparum , where effective immunity matures with age, the higher gametocyte densities in children induce higher levels of transmission reducing activity29.…”

Strategies & recent development of transmission-blocking vaccines against Plasmodium falciparum

“…Another important prefertilization antigen Pfs47 allows the parasite to evade the mosquito immune system by inhibiting the activation of apoptosis in mosquito midgut cells48. Beside all these characteristics, sexual stage antigens have also shown limited genetic polymorphism and strong potential for boosting the immune response424649. Further studies suggested that transmission blocking activity could likewise be obtained by targeting the mosquito components that are needed for the successful development of parasite inside the mosquito vector.…”

“…Radiolabelled antibodies against Pfs230 are able to bind to the surface of gametes and reduce the P. falciparum infectivity to mosquitoes7. Antibody responses against the Pfs230 were observed in naturally exposed individuals4243. The strong correlation between transmission blocking activity and anti-Pfs230 antibody response was found in Gambian30 and Papua New Guinean populations44.…”