Characterization of Naturally Acquired Immunity to a Panel of Antigens Expressed in Mature P. falciparum Gametocytes

IntroductionNaturally 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...

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Autores principales:	Michelle K. Muthui, Eizo Takashima, Brian R. Omondi, Christine Kinya, William I. Muasya, Hikaru Nagaoka, Kennedy W. Mwai, Benedict Orindi, Juliana Wambua, Teun Bousema, Chris Drakeley, Andrew M. Blagborough, Kevin Marsh, Philip Bejon, Melissa C. Kapulu
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	Plasmodium falciparum naturally acquired immunity mature gametocytes seroepidemiology malaria transmission Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/c65a10b1bdfc4a4abc25bc57b3f0bb60
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spelling	oai:doaj.org-article:c65a10b1bdfc4a4abc25bc57b3f0bb602021-11-12T05:39:33ZCharacterization of Naturally Acquired Immunity to a Panel of Antigens Expressed in Mature P. falciparum Gametocytes2235-298810.3389/fcimb.2021.774537https://doaj.org/article/c65a10b1bdfc4a4abc25bc57b3f0bb602021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcimb.2021.774537/fullhttps://doaj.org/toc/2235-2988IntroductionNaturally 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.MethodsAntigens 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.ResultsOf 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.ConclusionAge and concurrent parasitaemia remain important determinants of naturally acquired immunity to gametocyte antigens. Furthermore, we identify novel candidates for transmission-blocking activity evaluation.Michelle K. MuthuiEizo TakashimaBrian R. OmondiChristine KinyaWilliam I. MuasyaHikaru NagaokaKennedy W. MwaiKennedy W. MwaiBenedict OrindiJuliana WambuaTeun BousemaChris DrakeleyAndrew M. BlagboroughKevin MarshPhilip BejonPhilip BejonMelissa C. KapuluMelissa C. KapuluFrontiers Media S.A.articlePlasmodium falciparumnaturally acquired immunitymature gametocytesseroepidemiologymalaria transmissionMicrobiologyQR1-502ENFrontiers in Cellular and Infection Microbiology, Vol 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Plasmodium falciparum naturally acquired immunity mature gametocytes seroepidemiology malaria transmission Microbiology QR1-502
spellingShingle	Plasmodium falciparum naturally acquired immunity mature gametocytes seroepidemiology malaria transmission Microbiology QR1-502 Michelle K. Muthui Eizo Takashima Brian R. Omondi Christine Kinya William I. Muasya Hikaru Nagaoka Kennedy W. Mwai Kennedy W. Mwai Benedict Orindi Juliana Wambua Teun Bousema Chris Drakeley Andrew M. Blagborough Kevin Marsh Philip Bejon Philip Bejon Melissa C. Kapulu Melissa C. Kapulu Characterization of Naturally Acquired Immunity to a Panel of Antigens Expressed in Mature P. falciparum Gametocytes
description	IntroductionNaturally 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.MethodsAntigens 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.ResultsOf 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.ConclusionAge and concurrent parasitaemia remain important determinants of naturally acquired immunity to gametocyte antigens. Furthermore, we identify novel candidates for transmission-blocking activity evaluation.
format	article
author	Michelle K. Muthui Eizo Takashima Brian R. Omondi Christine Kinya William I. Muasya Hikaru Nagaoka Kennedy W. Mwai Kennedy W. Mwai Benedict Orindi Juliana Wambua Teun Bousema Chris Drakeley Andrew M. Blagborough Kevin Marsh Philip Bejon Philip Bejon Melissa C. Kapulu Melissa C. Kapulu
author_facet	Michelle K. Muthui Eizo Takashima Brian R. Omondi Christine Kinya William I. Muasya Hikaru Nagaoka Kennedy W. Mwai Kennedy W. Mwai Benedict Orindi Juliana Wambua Teun Bousema Chris Drakeley Andrew M. Blagborough Kevin Marsh Philip Bejon Philip Bejon Melissa C. Kapulu Melissa C. Kapulu
author_sort	Michelle K. Muthui
title	Characterization of Naturally Acquired Immunity to a Panel of Antigens Expressed in Mature P. falciparum Gametocytes
title_short	Characterization of Naturally Acquired Immunity to a Panel of Antigens Expressed in Mature P. falciparum Gametocytes
title_full	Characterization of Naturally Acquired Immunity to a Panel of Antigens Expressed in Mature P. falciparum Gametocytes
title_fullStr	Characterization of Naturally Acquired Immunity to a Panel of Antigens Expressed in Mature P. falciparum Gametocytes
title_full_unstemmed	Characterization of Naturally Acquired Immunity to a Panel of Antigens Expressed in Mature P. falciparum Gametocytes
title_sort	characterization of naturally acquired immunity to a panel of antigens expressed in mature p. falciparum gametocytes
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/c65a10b1bdfc4a4abc25bc57b3f0bb60
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Characterization of Naturally Acquired Immunity to a Panel of Antigens Expressed in Mature P. falciparum Gametocytes

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