Ikhlaq Hussain Kana1,2, Asier Garcia-Senosiain2, Susheel K Singh1,2, Régis Wendpayangde Tiendrebeogo1,2, Bishwanath Kumar Chourasia1,2, Pawan Malhotra3, Surya K Sharma4, Manoj K Das5, Subhash Singh6, Bright Adu7, Michael Theisen1,2. 1. Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark. 2. Centre for Medical Parasitology at Department of International Health, Immunology and Microbiology, University of Copenhagen and Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Denmark. 3. Malaria Biology Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, India. 4. National Institute of Malaria Research, Indian Council of Medical Research, New Delhi, India. 5. National Institute of Malaria Research, Field Unit, Ranchi (Jharkhand), India. 6. Indian Institute of Integrative Medicine, Canal Road, Jammu, India. 7. Noguchi Memorial Institute for Medical Research, University of Ghana, Legon.
Abstract
Background: The collection of clinical data from a tribal population in a malaria-endemic area of India suggests the occurrence of naturally acquired immunity (NAI) against Plasmodium falciparum malaria. Methods: Quantity and functionality of immunoglobulin G (IgG) antibodies against intact merozoites and recombinant proteins were assessed in a 13-month longitudinal cohort study of 121 individuals, 3-60 years of age. Results: Opsonic phagocytosis of merozoites activity was strongly associated (hazard ratio [HR] = 0.34; 95% confidence interval [CI] = .18-.66; P = .0013) with protection against febrile malaria. Of the different IgG subclasses, only IgG3 antibodies against intact whole merozoites was significantly associated with protection against febrile malaria (HR = 0.47; 95% CI = .26-.86; P = .01). Furthermore, a combination of IgG3 antibody responses against Pf12, MSP3.7, MSP3.3, and MSP2FC27 was strongly associated with protection against febrile malaria (HR = 0.15; 95% CI, .06-.37; P = .0001). Conclusions: These data suggest that NAI may, at least in part, be explained by opsonic phagocytosis of merozoites and IgG3 responses against whole merozoites, and in particular to a combination of 4 antigens is critical in this population. These results may have implications in the development of a subunit malaria vaccine. Opsonic phagocytosis of Plasmodium falciparum merozoites was associated with protection against clinical malaria in an India population. Antibody profiling identified four merozoite antigens (Pf12, MSP3.7, MSP3.3, and MSP2) as targets of protective Immunoglobuline G3 antibodies.
Background: The collection of clinical data from a tribal population in a malaria-endemic area of India suggests the occurrence of naturally acquired immunity (NAI) against Plasmodium falciparummalaria. Methods: Quantity and functionality of immunoglobulin G (IgG) antibodies against intact merozoites and recombinant proteins were assessed in a 13-month longitudinal cohort study of 121 individuals, 3-60 years of age. Results: Opsonic phagocytosis of merozoites activity was strongly associated (hazard ratio [HR] = 0.34; 95% confidence interval [CI] = .18-.66; P = .0013) with protection against febrile malaria. Of the different IgG subclasses, only IgG3 antibodies against intact whole merozoites was significantly associated with protection against febrile malaria (HR = 0.47; 95% CI = .26-.86; P = .01). Furthermore, a combination of IgG3 antibody responses against Pf12, MSP3.7, MSP3.3, and MSP2FC27 was strongly associated with protection against febrile malaria (HR = 0.15; 95% CI, .06-.37; P = .0001). Conclusions: These data suggest that NAI may, at least in part, be explained by opsonic phagocytosis of merozoites and IgG3 responses against whole merozoites, and in particular to a combination of 4 antigens is critical in this population. These results may have implications in the development of a subunit malaria vaccine. Opsonic phagocytosis of Plasmodium falciparum merozoites was associated with protection against clinical malaria in an India population. Antibody profiling identified four merozoite antigens (Pf12, MSP3.7, MSP3.3, and MSP2) as targets of protective Immunoglobuline G3 antibodies.
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