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Peripheral merozoite surface proteins are targets of naturally acquired immunity against malaria both in India and in Ghana.

Abstract

Development of a successful blood-stage vaccine against Plasmodium falciparum malaria remains a high priority. Immune-epidemiological studies are effective tools for the identification of antigenic-targets of naturally acquired immunity (NAI) against malaria. However, differences in study design and methodology may compromise inter-study comparisons. Here, we assessed antibody responses against intact merozoites and a panel of 24 recombinant merozoite antigens in longitudinal cohort studies of Ghanaian (n = 115) and Indian (n=121) populations using the same reagents and statistical methods. Anti-merozoites antibodies were associated with NAI in both the Indian (hazard ratio [lsqb]HR[rsqb] = 0.41, p = 0.020) and the Ghanaian (HR = 0.17, p < 0.001) participants. Of the 24 antigen-specific antibodies quantified, 12 and 8 were found to be protective in India and Ghana, respectively. Using LASSO regression, a powerful variable sub-selection technique, we identified subsets of four (MSP6, MSP3.7, MSPDBL2, and Pf12) and five (cMSP33D7, MSP3.3, MSPDBL1, GLURP-R2, and RALP-1) antigens which explained NAI better than the individual antibodies in India (HR=0.18, p< 0.001) and Ghana (HR=0.31, p< 0.001), respectively. IgG1 and/or IgG3 subclasses against five antigens from these subsets were associated with protection. Through this comparative study, maintaining uniformity of reagents and methodology, we demonstrate that NAI across diverse geographic regions may result from antibodies to multiple antigenic targets which constitute the peripheral merozoite surface protein complexes.

Authors+Show Affiliations

Centre for Medical Parasitology at Department of International Health, Immunology and Microbiology, University of Copenhagen and Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark.Centre for Medical Parasitology at Department of International Health, Immunology and Microbiology, University of Copenhagen and Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark.Centre for Medical Parasitology at Department of International Health, Immunology and Microbiology, University of Copenhagen and Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark.Centre for Medical Parasitology at Department of International Health, Immunology and Microbiology, University of Copenhagen and Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark.National Institute of Malaria Research, Field Unit, Ranchi (Jharkhand), India.Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Legon, Accra, Ghana.Indian Institute of Integrative Medicine, Canal Road, Jammu, India.Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Legon, Accra, Ghana.Centre for Medical Parasitology at Department of International Health, Immunology and Microbiology, University of Copenhagen and Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark mth@ssi.dk. Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31964745

Citation

Garcia-Senosiain, Asier, et al. "Peripheral Merozoite Surface Proteins Are Targets of Naturally Acquired Immunity Against Malaria Both in India and in Ghana." Infection and Immunity, 2020.
Garcia-Senosiain A, Kana IH, Singh SK, et al. Peripheral merozoite surface proteins are targets of naturally acquired immunity against malaria both in India and in Ghana. Infect Immun. 2020.
Garcia-Senosiain, A., Kana, I. H., Singh, S. K., Chourasia, B. K., Das, M. K., Dodoo, D., ... Theisen, M. (2020). Peripheral merozoite surface proteins are targets of naturally acquired immunity against malaria both in India and in Ghana. Infection and Immunity, doi:10.1128/IAI.00778-19.
Garcia-Senosiain A, et al. Peripheral Merozoite Surface Proteins Are Targets of Naturally Acquired Immunity Against Malaria Both in India and in Ghana. Infect Immun. 2020 Jan 21; PubMed PMID: 31964745.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Peripheral merozoite surface proteins are targets of naturally acquired immunity against malaria both in India and in Ghana. AU - Garcia-Senosiain,Asier, AU - Kana,Ikhlaq Hussain, AU - Singh,Susheel Kumar, AU - Chourasia,Bishwanath Kumar, AU - Das,Manoj Kumar, AU - Dodoo,Daniel, AU - Singh,Subhash, AU - Adu,Bright, AU - Theisen,Michael, Y1 - 2020/01/21/ PY - 2020/1/23/entrez JF - Infection and immunity JO - Infect. Immun. N2 - Development of a successful blood-stage vaccine against Plasmodium falciparum malaria remains a high priority. Immune-epidemiological studies are effective tools for the identification of antigenic-targets of naturally acquired immunity (NAI) against malaria. However, differences in study design and methodology may compromise inter-study comparisons. Here, we assessed antibody responses against intact merozoites and a panel of 24 recombinant merozoite antigens in longitudinal cohort studies of Ghanaian (n = 115) and Indian (n=121) populations using the same reagents and statistical methods. Anti-merozoites antibodies were associated with NAI in both the Indian (hazard ratio [lsqb]HR[rsqb] = 0.41, p = 0.020) and the Ghanaian (HR = 0.17, p < 0.001) participants. Of the 24 antigen-specific antibodies quantified, 12 and 8 were found to be protective in India and Ghana, respectively. Using LASSO regression, a powerful variable sub-selection technique, we identified subsets of four (MSP6, MSP3.7, MSPDBL2, and Pf12) and five (cMSP33D7, MSP3.3, MSPDBL1, GLURP-R2, and RALP-1) antigens which explained NAI better than the individual antibodies in India (HR=0.18, p< 0.001) and Ghana (HR=0.31, p< 0.001), respectively. IgG1 and/or IgG3 subclasses against five antigens from these subsets were associated with protection. Through this comparative study, maintaining uniformity of reagents and methodology, we demonstrate that NAI across diverse geographic regions may result from antibodies to multiple antigenic targets which constitute the peripheral merozoite surface protein complexes. SN - 1098-5522 UR - https://www.unboundmedicine.com/medline/citation/31964745/Peripheral_merozoite_surface_proteins_are_targets_of_naturally_acquired_immunity_against_malaria_both_in_India_and_in_Ghana L2 - http://iai.asm.org/cgi/pmidlookup?view=long&amp;pmid=31964745 DB - PRIME DP - Unbound Medicine ER -