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Plasmodium falciparum Cysteine-Rich Protective Antigen (CyRPA) Elicits Detectable Levels of Invasion-Inhibitory Antibodies during Natural Infection in Humans.
Mian, Syed Yusuf; Somanathan, Anjali; Chaddha, Kritika; Pandey, Alok K; Singh, Hina; Krishna, Sri; Chaturvedi, Neha; Uchoi, Seemalata; Shukla, Man Mohan; Bharti, Praveen K; Singh, Neeru; Chauhan, Virander Singh; Gaur, Deepak.
Afiliação
  • Mian SY; Laboratory of Malaria and Vaccine Research, School of Biotechnology, Jawaharlal Nehru University, New Delhi, India.
  • Somanathan A; Laboratory of Malaria and Vaccine Research, School of Biotechnology, Jawaharlal Nehru University, New Delhi, India.
  • Chaddha K; Laboratory of Malaria and Vaccine Research, School of Biotechnology, Jawaharlal Nehru University, New Delhi, India.
  • Pandey AK; Malaria Group, International Centre for Genetic Engineering and Biotechnologygrid.425195.e (ICGEB), New Delhi, India.
  • Singh H; Malaria Group, International Centre for Genetic Engineering and Biotechnologygrid.425195.e (ICGEB), New Delhi, India.
  • Krishna S; ICMR-National Institute of Research in Tribal Health (NIRTH), Jabalpur, Madhya Pradesh, India.
  • Chaturvedi N; ICMR-National Institute of Research in Tribal Health (NIRTH), Jabalpur, Madhya Pradesh, India.
  • Uchoi S; Laboratory of Malaria and Vaccine Research, School of Biotechnology, Jawaharlal Nehru University, New Delhi, India.
  • Shukla MM; ICMR-National Institute of Research in Tribal Health (NIRTH), Jabalpur, Madhya Pradesh, India.
  • Bharti PK; ICMR-National Institute of Research in Tribal Health (NIRTH), Jabalpur, Madhya Pradesh, India.
  • Singh N; ICMR-National Institute of Research in Tribal Health (NIRTH), Jabalpur, Madhya Pradesh, India.
  • Chauhan VS; Malaria Group, International Centre for Genetic Engineering and Biotechnologygrid.425195.e (ICGEB), New Delhi, India.
  • Gaur D; Laboratory of Malaria and Vaccine Research, School of Biotechnology, Jawaharlal Nehru University, New Delhi, India.
Infect Immun ; 90(1): e0037721, 2022 01 25.
Article em En | MEDLINE | ID: mdl-34694918
Plasmodium falciparum cysteine-rich protective antigen (CyRPA) is a conserved component of an essential erythrocyte invasion complex (RH5/Ripr/CyRPA) and a target of potent cross-strain parasite-neutralizing antibodies. While naturally acquired human RH5 antibodies have been functionally characterized, there are no similar reports on CyRPA. Thus, we analyzed the parasite-neutralizing activity of naturally acquired human CyRPA antibodies. In this regard, CyRPA human antibodies were measured and purified from malaria-infected plasma obtained from patients in central India and analyzed for their parasite neutralizing activity via in vitro growth inhibition assays (GIA). We report that, despite being susceptible to antibodies, CyRPA is a highly conserved antigen that does not appear to be under substantial immune selection pressure, as a very low acquisition rate for anti-CyRPA antibodies was reported in malaria-exposed Indians. We demonstrate for the first time that the small amounts of natural CyRPA antibodies exhibited functional parasite-neutralizing activity and that a CyRPA-based vaccine formulation induces highly potent antibodies in rabbits. Importantly, the vaccine-induced CyRPA antibodies exhibited a robust 50% inhibitory concentration (IC50) of 21.96 µg/ml, which is comparable to the IC50 of antibodies against the leading blood-stage vaccine candidate, reticulocyte-binding-like homologous protein 5 (RH5). Our data support CyRPA as a unique vaccine target that is highly susceptible to immune attack but is highly conserved compared to other leading candidates such as MSP-1 and AMA-1, further substantiating its promise as a leading blood-stage vaccine candidate.
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Texto completo: 1 Coleções: 01-internacional Contexto em Saúde: 3_ND Base de dados: MEDLINE Assunto principal: Plasmodium falciparum / Anticorpos Antiprotozoários / Proteínas de Protozoários / Malária Falciparum / Interações Hospedeiro-Parasita / Antígenos de Protozoários Limite: Humans Idioma: En Revista: Infect Immun Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Contexto em Saúde: 3_ND Base de dados: MEDLINE Assunto principal: Plasmodium falciparum / Anticorpos Antiprotozoários / Proteínas de Protozoários / Malária Falciparum / Interações Hospedeiro-Parasita / Antígenos de Protozoários Limite: Humans Idioma: En Revista: Infect Immun Ano de publicação: 2022 Tipo de documento: Article