TY - JOUR
T1 - Cytophilic antibodies against key plasmodium falciparum blood stage antigens contribute to protection against clinical malaria in a high transmission region of eastern India
AU - Kana, Ikhlaq Hussain
AU - Garcia-Senosiain, Asier
AU - Singh, Susheel K.
AU - Tiendrebeogo, Régis Wendpayangde
AU - Chourasia, Bishwanath Kumar
AU - Malhotra, Pawan
AU - Sharma, Surya K.
AU - Das, Manoj K.
AU - Singh, Subhash
AU - Adu, Bright
AU - Theisen, Michael
N1 - Publisher Copyright:
© The Author(s) 2018.
PY - 2018/8/14
Y1 - 2018/8/14
N2 - 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.
AB - 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.
KW - Merozoites antigens
KW - Naturally acquired immunity
KW - Opsonic phagocytosis
UR - http://www.scopus.com/inward/record.url?scp=85054982569&partnerID=8YFLogxK
U2 - 10.1093/infdis/jiy258
DO - 10.1093/infdis/jiy258
M3 - Article
C2 - 29733355
AN - SCOPUS:85054982569
SN - 0022-1899
VL - 218
SP - 956
EP - 965
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 6
ER -