Functional Characterization and Comparison of Plasmodium falciparum Proteins as Targets of Transmission-blocking Antibodies

Nikolaeva, Daria; Illingworth, Joseph J.; Miura, Kazutoyo; Alanine, Daniel G. W.; Brian, Iona J.; Li, Yuanyuan; Fyfe, Alex; Da, Dari F.; Cohuet, Anna; Long, Carole A.; Draper, Simon J.; Biswas, Sumi

doi:10.1074/mcp.ra117.000036

Cited by 15 publications

(13 citation statements)

References 63 publications

(60 reference statements)

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“…Alternatively, rabbit antiserum was obtained from immunized rabbit with recombinant AGAP006398 (Noble Sciences, Inc). IgG from mouse and rabbit sera was purified as previously described (39).…”

Section: Methodsmentioning

confidence: 99%

Plasmodium falciparum evades immunity of anopheline mosquitoes by interacting with a Pfs47 midgut receptor

Molina-Cruz

Canepa

Silva

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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The surface protein Pfs47 allows Plasmodium falciparum parasites to survive and be transmitted by making them “undetectable” to the mosquito immune system. P. falciparum parasites express Pfs47 haplotypes compatible with their sympatric vectors, while those with incompatible haplotypes are eliminated by the mosquito. We proposed that Pfs47 serves as a “key” that mediates immune evasion by interacting with a mosquito receptor “the lock,” which differs in evolutionarily divergent anopheline mosquitoes. Recombinant Pfs47 (rPfs47) was used to identify the mosquito Pfs47 receptor protein (P47Rec) using far-Western analysis. rPfs47 bound to a single 31-kDa band and the identity of this protein was determined by mass spectrometry. The mosquito P47Rec has two natterin-like domains and binds to Pfs47 with high affinity (17 to 32 nM). P47Rec is a highly conserved protein with submicrovillar localization in midgut cells. It has structural homology to a cytoskeleton-interacting protein and accumulates at the site of ookinete invasion. Silencing P47Rec expression reduced P. falciparum infection, indicating that the interaction of Pfs47 with the receptor is critical for parasite survival. The binding specificity of P47Rec from distant anophelines (Anopheles gambiae, Anopheles dirus, and Anopheles albimanus) with Pfs47-Africa (GB4) and Pfs47-South America (7G8) haplotypes was evaluated, and it is in agreement with the previously documented compatibility between P. falciparum parasites expressing different Pfs47 haplotypes and these three anopheline species. Our findings give further support to the role of Pfs47 in the adaptation of P. falciparum to different vectors.

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Section: Methodsmentioning

confidence: 99%

Plasmodium falciparum evades immunity of anopheline mosquitoes by interacting with a Pfs47 midgut receptor

Molina-Cruz

Canepa

Silva

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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“…Though the association was not significant, we did observe modest evidence for increased prevalence of antibodies to Pfs230 and Pfs48/45 following the malaria transmission season. The potential for boosting of vaccine-induced immune responses during natural infection would enhance vaccine efficacy in the field (57). The extent and implications of this boosting are yet to be explored, presenting an interesting question for future studies.…”

Section: Discussionmentioning

confidence: 99%

Immune Responses to Gametocyte Antigens in a Malaria Endemic Population—The African falciparum Context: A Systematic Review and Meta-Analysis

et al. 2019

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Background: Malaria elimination remains a priority research agenda with the need for interventions that reduce and/or block malaria transmission from humans to mosquitoes. Transmission-blocking vaccines (TBVs) are in development, most of which target the transmission stage (i.e., gametocyte) antigens Pfs230 and Pfs48/45. For these interventions to be implemented, there is a need to understand the naturally acquired immunity to gametocytes. Several studies have measured the prevalence of immune responses to Pfs230 and Pfs48/45 in populations in malaria-endemic areas.Methods: We conducted a systematic review of studies carried out in African populations that measured the prevalence of immune responses to the gametocyte antigens Pfs230 and Pfs48/45. We assessed seroprevalence of antibody responses to the two antigens and investigated the effects of covariates such as age, transmission intensity/endemicity, season, and parasite prevalence on the prevalence of these antibody responses by meta-regression.Results: We identified 12 studies covering 23 sites for inclusion in the analysis. We found that the range of reported seroprevalence to Pfs230 and Pfs48/45 varied widely across studies, from 0 to 64% for Pfs48/45 and from 6 to 72% for Pfs230. We also found a modest association between increased age and increased seroprevalence to Pfs230: adults were associated with higher seroprevalence estimates in comparison to children (β coefficient 0.21, 95% CI: 0.05–0.38, p = 0.042). Methodological factors were the most significant contributors to heterogeneity between studies which prevented calculation of pooled prevalence estimates.Conclusions: Naturally acquired sexual stage immunity, as detected by antibodies to Pfs230 and Pfs48/45, was present in most studies analyzed. Significant between-study heterogeneity was seen, and methodological factors were a major contributor to this, and prevented further analysis of epidemiological and biological factors. This demonstrates a need for standardized protocols for conducting and reporting seroepidemiological analyses.

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“…However, they reduce the risk of transmission to other people by the mosquito vector and by so doing favor herd immunity; as such they have sometimes been referred to as altruistic vaccines (95). Two groups of target antigens (gene superfamilies) exist, namely pre-fertilization and post-fertilization antigens (Table 1 and Figure 2) (48, 97, 107–111, 121). The list (Table 1) is not exhaustive both for pre- and post-fertilization antigens as some proteins remain unidentified to date.…”

Section: Anti-gametocyte and Anti-gamete Transmission Blocking Vaccinesmentioning

confidence: 99%

“…Hence the necessity to pursue studies with the Pfs 48/45 TBV candidate. Moreover, recent studies have identified new sexual stage antigens that require more attention (48, 121)…”

Section: Anti-gametocyte and Anti-gamete Transmission Blocking Vaccinesmentioning

confidence: 99%

Immune Responses to the Sexual Stages of Plasmodium falciparum Parasites

et al. 2019

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Malaria infections remain a serious global health problem in the world, particularly among children and pregnant women in Sub-Saharan Africa. Moreover, malaria control and elimination is hampered by rapid development of resistance by the parasite and the vector to commonly used antimalarial drugs and insecticides, respectively. Therefore, vaccine-based strategies are sorely needed, including those designed to interrupt disease transmission. However, a prerequisite for such a vaccine strategy is the understanding of both the human and vector immune responses to parasite developmental stages involved in parasite transmission in both man and mosquito. Here, we review the naturally acquired humoral and cellular responses to sexual stages of the parasite while in the human host and the Anopheles vector. In addition, updates on current anti-gametocyte, anti-gamete, and anti-mosquito transmission blocking vaccines are given. We conclude with our views on some important future directions of research into P. falciparum sexual stage immunity relevant to the search for the most appropriate transmission-blocking vaccine.

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Functional Characterization and Comparison of Plasmodium falciparum Proteins as Targets of Transmission-blocking Antibodies

Cited by 15 publications

References 63 publications

Plasmodium falciparum evades immunity of anopheline mosquitoes by interacting with a Pfs47 midgut receptor

Plasmodium falciparum evades immunity of anopheline mosquitoes by interacting with a Pfs47 midgut receptor

Immune Responses to Gametocyte Antigens in a Malaria Endemic Population—The African falciparum Context: A Systematic Review and Meta-Analysis

Immune Responses to the Sexual Stages of Plasmodium falciparum Parasites

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