Immune Responses to Defined Plasmodium falciparum Antigens and Disease Susceptibility in Two Subpopulations of Northern India
Keywords:
Malaria, P. falciparum, antigen, peptide, ELISA, Immune responseAbstract
The aim of this study was to investigate the prevalence of naturally acquired immune response to malaria in individuals of different age groups belonging to areas of northern India, Loni PHC (LN) and Dhaulana PHC (SD) of district Ghaziabad. Plasmodium falciparum-infected erythrocyte lysate and six synthetic peptides from different stages of P. falciparum (CSP, MSP1, AMA1, RAP1, EBA175 and PfG27) were used to determine both humoral and cellular immune responses. Plasma of individual subject was also analyzed for IL-4, IL-10, IFN-γ and TNF-α level. We observed an age-wise increasing trend of immunity in these two populations. There was a significant association between the number of antibody responders and recognition of stage-specific epitopes by antibodies. Peripheral blood mononuclear cells of more than 75% of individuals proliferated in response to stimulation by all the antigens in LN area. IL-4 and IL-10 responses were significantly higher in individuals of LN Area; whereas IFN-g and TNF-a responses were higher in individuals of SD Area. It was also noticed that the frequency of responders to stage-specific antigens was higher in individuals from the LN area where the frequency of malaria was lower. The naturally acquired immune responses to P. falciparum antigens reflected the reduced risk of malaria in the study groups. The results demonstrated immunogenicity of the epitopes to P. falciparum in population of this endemic zone.
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Biswas, S., Seth, R.K., Tyagi, P.K., Sharma, S.K. & Dash, A.P. (2008). Naturally acquired immunity and reduced susceptibility to falciparum malaria in two subpopulations of endemic eastern India. Scand. J. Immunol., 67(2): 177–184. https://doi.org/10.1111/j.1365-3083.2007.02047.x.
Seth, R.K., Bhat, A.A., Rao, D.N. & Biswas, S. (2010). Acquired immune response to defined Plasmodium vivax antigens in individuals residing in northern India. Microbes Infect., 12(3): 199–206. https://doi.org/10.1016/j.micinf.2009.12.006.
Baird, J.K., Jones, T.R., Danudirgo, E.W., Annis, B.A., Bangs, M.J., Basri, H., Purnomo & Masbar, S. (1991). Age-dependent acquired protection against Plasmodium falciparum in people having two years exposure to hyperendemic malaria. Am. J. Trop. Med. Hyg., 45(1): 65–76. https://doi.org/10.4269/ajtmh.1991.45.65.
al-Yaman, F., Genton, B., Anders, R.F., Falk, M., Triglia, T., Lewis, D., Hii, J., Beck, H.P. & Alpers, M.P. (1994). Relationship between humoral response to Plasmodium falciparum merozoite surface antigen-2 and malaria morbidity in a highly endemic area of Papua New Guinea. Am. J. Trop. Med. Hyg., 51(5): 593–602. https://doi.org/10.4269/ajtmh.1994.51.593.
Nwagwu, M., Anumudu, C.A., Sodeinde, O., Ologunde, C.A., Obi, T.U., Wirtz, R.A., Gordon, D.M. & Lyon, J.A. (1998). Identification of a subpopulation of immune Nigerian adult volunteers by antibodies to the circumsporozoite protein of Plasmodium falciparum. Am. J. Trop. Med. Hyg., 58(5): 684–692. https://doi.org/10.4269/ajtmh.1998.58.684.
Perlmann, P. & Troye-Blomberg, M. (2002). Malaria and the immune system in humans. Chem. Immunol., 80: 229–242. https://doi.org/10.1159/000058846.
Nussenzweig, V. & Nussenzweig, R.S. (1986). Development of a sporozoite malaria vaccine. Am. J. Trop. Med. Hyg., 35(4): 678–688. https://doi.org/10.4269/ajtmh.1986.35.678.
Lal, A.A., Hughes, M.A., Oliveira, D.A., Nelson, C., Bloland, P.B., Oloo, A.J., Hawley, W.E., Hightower, A.W., Nahlen, B.L. & Udhayakumar, V. (1996). Identification of T-cell determinants in natural immune responses to the Plasmodium falciparum apical membrane antigen (AMA-1) in an adult population exposed to malaria. Infect. Immun., 64(3): 1054–1059. https://doi.org/10.1128/IAI.64.3.1054-1059.1996.
Holder, A.A. (1996). Preventing merozoite invasion of erythrocytes. In: Hoffman, S.L. (ed), Malaria Vaccine Development: A Multi-Immune Response Approach. ASM Press, Washington DC. pp. 77–104.
Harnyuttanakorn, P., McBride, J.S., Donachie, S., Heidrich, H.G. & Ridley, R.G. (1992). Inhibitory monoclonal antibodies recognise epitopes adjacent to a proteolytic cleavage site on the RAP-1 protein of Plasmodium falciparum. Mol. Biochem. Parasitol., 55(1-2): 177–186. https://doi.org/10.1016/0166-6851(92)90138-a.
Riley, E.M., Allen, S.J., Wheeler, J.G., Blackman, M.J., Bennett, S., Takacs, B., Schönfeld, H.J., Holder, A.A. & Greenwood, B.M. (1992). Naturally acquired cellular and humoral immune responses to the major merozoite surface antigen (PfMSP1) of Plasmodium falciparum are associated with reduced malaria morbidity. Parasite Immunol., 14(3): 321–337. https://doi.org/10.1111/j.1365-3024.1992.tb00471.x.
Sim, B.K., Carter, J.M., Deal, C.D., Holland, C., Haynes, J.D. & Gross, M. (1994). Plasmodium falciparum: further characterization of a functionally active region of the merozoite invasion ligand EBA-175. Exp. Parasitol., 78(3): 259–268. https://doi.org/10.1006/expr.1994.1027.
Udhayakumar, V., Anyona, D., Kariuki, S., Shi, Y.P., Bloland, P.B., Branch, O.H., Weiss, W., Nahlen, B.L., Kaslow, D.C. & Lal, A.A. (1995). Identification of T and B cell epitopes recognized by humans in the C-terminal 42-kDa domain of the Plasmodium falciparum merozoite surface protein (MSP)-1. J. Immunol., 154(11): 6022–6030.
Jakobsen, P.H., Kurtzhals, J.A., Riley, E.M., Hviid, L., Theander, T.G., Morris-Jones, S., Jensen, J.B., Bayoumi, R.A., Ridley, R.G. & Greenwood, B.M. (1997). Antibody responses to Rhoptry-Associated Protein-1 (RAP-1) of Plasmodium falciparum parasites in humans from areas of different malaria endemicity. Parasite Immunol., 19(9): 387–393. https://doi.org/10.1046/j.1365-3024.1997.d01-234.x.
Okenu, D.M., Riley, E.M., Bickle, Q.D., Agomo, P.U., Barbosa, A., Daugherty, J.R., Lanar, D.E. & Conway, D.J. (2000). Analysis of human antibodies to erythrocyte binding antigen 175 of Plasmodium falciparum. Infect. Immun., 68(10): 5559–5566. https://doi.org/10.1128/iai.68.10.5559-5566.2000.
Ballou, W.R., Hoffman, S.L., Sherwood, J.A., Hollingdale, M.R., Neva, F.A., Hockmeyer, W.T., Gordon, D.M., Schneider, I., Wirtz, R.A. & Young, J.F. (1987). Safety and efficacy of a recombinant DNA Plasmodium falciparum sporozoite vaccine. Lancet, 1(8545): 1277–1281. https://doi.org/10.1016/s0140-6736(87)90540-x.
Herrington, D.A., Clyde, D.F., Losonsky, G., Cortesia, M., Murphy, J.R., Davis, J., Baqar, S., Felix, A.M., Heimer, E.P. & Gillessen, D. (1987). Safety and immunogenicity in man of a synthetic peptide malaria vaccine against Plasmodium falciparum sporozoites. Nature, 328(6127): 257–259. https://doi.org/10.1038/328257a0.
Stoute, J.A., Slaoui, M., Heppner, D.G., Momin, P., Kester, K.E., Desmons, P., Wellde, B.T., Garçon, N., Krzych, U. & Marchand, M. (1997). A preliminary evaluation of a recombinant circumsporozoite protein vaccine against Plasmodium falciparum malaria. RTS,S Malaria Vaccine Evaluation Group. N. Engl. J. Med., 336(2): 86–91. https://doi.org/10.1056/NEJM199701093360202.
Alloueche, A., Milligan, P., Conway, D.J., Pinder, M., Bojang, K., Doherty, T., Tornieporth, N., Cohen, J. & Greenwood, B.M. (2003). Protective efficacy of the RTS,S/AS02 Plasmodium falciparum malaria vaccine is not strain specific. Am. J. Trop. Med. Hyg., 68(1): 97–101. https://doi.org/10.4269/ajtmh.2003.68.97.
Kaslow, D.C. (1997). Transmission-blocking vaccines: uses and current status of development. Int. J. Parasitol., 27(2): 183–189. https://doi.org/10.1016/s0020-7519(96)00148-8.
Tsuboi, T., Tachibana, M., Kaneko, O. & Torii, M. (2003). Transmission-blocking vaccine of vivax malaria. Parasitol. Int., 52(1): 1–11. https://doi.org/10.1016/s1383-5769(02)00037-5.
Newton, C.R. & Krishna, S. (1998). Severe falciparum malaria in children: current understanding of pathophysiology and supportive treatment. Pharmacol. Ther., 79(1): 1–53. https://doi.org/10.1016/s0163-7258(98)00008-4.
Jason, J., Archibald, L.K., Nwanyanwu, O.C., Bell, M., Buchanan, I., Larned, J., Kazembe, P.N., Dobbie, H., Parekh, B., Byrd, M.G., Eick, A., Han, A. & Jarvis, W.R. (2001). Cytokines and malaria parasitemia. Clin. Immunol., 100(2): 208–218. https://doi.org/10.1006/clim.2001.5057.
Dodoo, D., Omer, F.M., Todd, J., Akanmori, B.D., Koram, K.A. & Riley, E.M. (2002). Absolute levels and ratios of proinflammatory and anti-inflammatory cytokine production in vitro predict clinical immunity to Plasmodium falciparum malaria. J. Infect. Dis., 185(7): 971–979. https://doi.org/10.1086/339408.
Day, N.P., Hien, T.T., Schollaardt, T., Loc, P.P., Chuong, L.V., Chau, T.T., Mai, N.T., Phu, N.H., Sinh, D.X., White, N.J. & Ho, M. (1999). The prognostic and pathophysiologic role of pro- and antiinflammatory cytokines in severe malaria. J. Infect. Dis., 180(4): 1288–1297. https://doi.org/10.1086/315016.
Torre, D., Speranza, F., Giola, M., Matteelli, A., Tambini, R. & Biondi, G. (2002). Role of Th1 and Th2 cytokines in immune response to uncomplicated Plasmodium falciparum malaria. Clin. Diagn. Lab. Immunol., 9(2): 348–351. https://doi.org/10.1128/cdli.9.2.348-351.2002.
Lyke, K.E., Burges, R., Cissoko, Y., Sangare, L., Dao, M., Diarra, I., Kone, A., Harley, R., Plowe, C.V., Doumbo, O.K. & Sztein, M.B. (2004). Serum levels of the proinflammatory cytokines interleukin-1 beta (IL-1beta), IL-6, IL-8, IL-10, tumor necrosis factor alpha, and IL-12(p70) in Malian children with severe Plasmodium falciparum malaria and matched uncomplicated malaria or healthy controls. Infect. Immun., 72(10): 5630–5637. https://doi.org/10.1128/IAI.72.10.5630-5637.2004.
Deloron, P., Chougnet, C., Lepers, J.P., Tallet, S. & Coulanges, P. (1991). Protective value of elevated levels of gamma interferon in serum against exoerythrocytic stages of Plasmodium falciparum. J. Clin. Microbiol., 29(9): 1757–1760. https://doi.org/10.1128/JCM.29.9.1757-1760.1991.
Clark, I.A. & Cowden, W.B. (1999). Why is the Pathology of Falciparum Worse than that of Vivax Malaria? Parasitol. Today, 15(11): 458–461. https://doi.org/10.1016/S0169-4758(99)01535-5.
Miller, L.H., Baruch, D.I., Marsh, K. & Doumbo, O.K. (2002). The pathogenic basis of malaria. Nature, 415(6872): 673–679. https://doi.org/10.1038/415673a.
Sharma, V.P. (2012). Battling malaria iceberg incorporating strategic reforms in achieving Millennium Development Goals & malaria elimination in India. Indian J. Med. Res., 136(6): 907–925.
Biswas, S. (2000). Formation of Plasmodium falciparum gametocytes in vivo and in vitro relates to transmission intensity. Ann. Trop. Med. Parasitol., 94(5): 437–446. https://doi.org/10.1080/00034983.2000.11813562.
Biswas, S. (2004). Inter-test comparison between filter paper absorbed blood eluate and serum for malaria serology by enzyme immunoassay: an operational feasibility. J. Immunoassay Immunochem., 25(4): 399–410. https://doi.org/10.1081/ias-200033853.
Trager, W. & Jensen, J.B. (1976). Human malaria parasites in continuous culture. Science, 193(4254): 673–675. https://doi.org/10.1126/science.781840.
Avrameas, S. & Ternynck, T. (1969). The cross-linking of proteins with glutaraldehyde and its use for the preparation of immunoadsorbents. Immunochemistry, 6(1): 53–66. https://doi.org/10.1016/0019-2791(69)90178-5.
Shi, Y.P., Das, P., Holloway, B., Udhayakumar, V., Tongren, J.E., Candal, F., Biswas, S., Ahmad, R., Hasnain, S.E. & Lal, A.A. (2000). Development, expression, and murine testing of a multistage Plasmodium falciparum malaria vaccine candidate. Vaccine, 18(25): 2902–2914. https://doi.org/10.1016/s0264-410x(00)00045-1.
Biswas, S., Tomar, D. & Rao, D.N. (2005). Investigation of the kinetics of histidine-rich protein 2 and of the antibody responses to this antigen, in a group of malaria patients from India. Ann. Trop. Med. Parasitol., 99(6): 553–562. https://doi.org/10.1179/136485905X51463.
Mlambo, G., Mutambu, S.L., Mduluza, T., Soko, W., Mbedzi, J., Chivenga, J., Lanar, D.E., Singh, S., Carucci, D., Gemperli, A. & Kumar, N. (2006). Antibody responses to Plasmodium falciparum vaccine candidate antigens in three areas distinct with respect to altitude. Acta Trop., 100(1-2): 70–78. https://doi.org/10.1016/j.actatropica.2006.09.012.
Noone, C., Parkinson, M., Dowling, D.J., Aldridge, A., Kirwan, P., Molloy, S.F., Asaolu, S.O., Holland, C. & O'Neill, S.M. (2013). Plasma cytokines, chemokines and cellular immune responses in pre-school Nigerian children infected with Plasmodium falciparum. Malar. J., 12: 5. https://doi.org/10.1186/1475-2875-12-5.
Bretscher, M.T., Supargiyono, S., Wijayanti, M.A., Nugraheni, D., Widyastuti, A.N., Lobo, N.F., Hawley, W.A., Cook, J. & Drakeley, C.J. (2013). Measurement of Plasmodium falciparum transmission intensity using serological cohort data from Indonesian schoolchildren. Malar. J., 12: 21. https://doi.org/10.1186/1475-2875-12-21.
Troye-Blomberg, M., Berzins, K. & Perlmann, P. (1994). T-cell control of immunity to the asexual blood stages of the malaria parasite. Crit. Rev. Immunol., 14(2): 131–155. https://doi.org/10.1615/critrevimmunol.v14.i2.20.
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