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dc.contributor.authorMuthui, Michelle K
dc.contributor.authorTakashima, Eizo
dc.contributor.authorOmondi, Brian R
dc.contributor.authorKinya, Christine
dc.contributor.authorMuasya, William I
dc.contributor.authorNagaoka, Hikaru
dc.contributor.authorMwai, Kennedy W
dc.contributor.authorOrindi, Benedict
dc.contributor.authorWambua, Juliana
dc.contributor.authorBousema, Teun
dc.contributor.authorDrakeley, Chris
dc.contributor.authorBlagborough, Andrew Michael
dc.contributor.authorMarsh, Kevin
dc.contributor.authorBejon, Philip
dc.contributor.authorKapulu, Melissa C
dc.date.accessioned2021-12-15T11:11:54Z
dc.date.available2021-12-15T11:11:54Z
dc.date.issued2021
dc.date.submitted2021-09-12
dc.identifier.issn2235-2988
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/331481
dc.description.abstractIntroduction: Naturally acquired immune responses against antigens expressed on the surface of mature gametocytes develop in individuals living in malaria-endemic areas. Evidence suggests that such anti-gametocyte immunity can block the development of the parasite in the mosquito, thus playing a role in interrupting transmission. A better comprehension of naturally acquired immunity to these gametocyte antigens can aid the development of transmission-blocking vaccines and improve our understanding of the human infectious reservoir. Methods: Antigens expressed on the surface of mature gametocytes that had not previously been widely studied for evidence of naturally acquired immunity were identified for protein expression alongside Pfs230-C using either the mammalian HEK293E or the wheat germ cell-free expression systems. Where there was sequence variation in the candidate antigens (3D7 vs a clinical isolate PfKE04), both variants were expressed. ELISA was used to assess antibody responses against these antigens, as well as against crude stage V gametocyte extract (GE) and AMA1 using archived plasma samples from individuals recruited to participate in malaria cohort studies. We analyzed antibody levels (estimated from optical density units using a standardized ELISA) and seroprevalence (defined as antibody levels greater than three standard deviations above the mean levels of a pool of malaria naïve sera). We described the dynamics of antibody responses to these antigens by identifying factors predictive of antibody levels using linear regression models. Results: Of the 25 antigens selected, seven antigens were produced successfully as recombinant proteins, with one variant antigen, giving a total of eight proteins for evaluation. Antibodies to the candidate antigens were detectable in the study population (N = 216), with seroprevalence ranging from 37.0% (95% CI: 30.6%, 43.9%) for PSOP1 to 77.8% (95% CI: 71.6%, 83.1%) for G377 (3D7 variant). Responses to AMA1 and GE were more prevalent than those to the gametocyte proteins at 87.9% (95% CI: 82.8%, 91.9%) and 88.3% (95% CI: 83.1%, 92.4%), respectively. Additionally, both antibody levels and breadth of antibody responses were associated with age and concurrent parasitaemia. Conclusion: Age and concurrent parasitaemia remain important determinants of naturally acquired immunity to gametocyte antigens. Furthermore, we identify novel candidates for transmission-blocking activity evaluation.
dc.languageen
dc.publisherFrontiers Media SA
dc.subjectCellular and Infection Microbiology
dc.subjectPlasmodium falciparum
dc.subjectnaturally acquired immunity
dc.subjectmature gametocytes
dc.subjectseroepidemiology
dc.subjectmalaria transmission
dc.titleCharacterization of Naturally Acquired Immunity to a Panel of Antigens Expressed in Mature P. falciparum Gametocytes.
dc.typeArticle
dc.date.updated2021-12-15T11:11:53Z
prism.publicationNameFront Cell Infect Microbiol
prism.volume11
dc.identifier.doi10.17863/CAM.78935
dcterms.dateAccepted2021-10-25
rioxxterms.versionofrecord10.3389/fcimb.2021.774537
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
dc.identifier.eissn2235-2988
pubs.funder-project-idMedical Research Council (MR/N00227X/1)
cam.issuedOnline2021-11-12


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