Humoral immune response to Plasmodium falciparum vaccine candidate GMZ2 and its components in populations naturally exposed to seasonal malaria in Ethiopia
详细信息 查看全文
- 作者：Hassen Mamo (1)
Meral Esen (2) (3)
Anthony Ajua (2) (3)
Michael Theisen (4) (5)
Benjamin Mordmüller (2) (3)
Beyene Petros (1) - 关键词：Plasmodium falciparum ; Malaria ; Ig ; ELISA ; Ethiopia ; Vaccine ; Antigen ; Cytophilic ; Noncytophilic
- 刊名：Malaria Journal
- 出版年：2013
- 出版时间：December 2013
- 年：2013
- 卷：12
- 期：1
- 全文大小：1049KB
- 参考文献：1. WHO: / World Malaria Report. 2010. http://www.who.int/malaria
2. Agnandji ST, Lell B, Soulanoudjingar SS, Fernandes JF, Abossolo BP, Conzelmann C, Nfono BG, Methogo O, Doucka Y, Flamen A, Mordmüller B, Issifou S, Kremsner PG, Sacarlal J, Aide P, Lanaspa M, Aponte JJ, Nhamuave A, Quelhas D, Bassat Q, Mandjate S, Macete E, Alonso P, Abdulla S, Salim N, Juma O, Shomari M, Shubis K, Machera F, Hamad AS: First results of Phase 3 trial of RTS,S/AS01 malaria vaccine in African children. / N Engl J Med 2011, 365:1863-875. CrossRef
3. Ogutu BR, Apollo OJ, McKinney D, Okoth W, Siangla J, Dubovsky F, Tucker K, Waitumbi JN, Diggs C, Wittes J, Malkin E, Leach A, Soisson LA, Milman JB, Otieno L, Holland CA, Polhemus M, Remich SA, Ockenhouse CF, Cohen J, Ballou WR, Martin SK, Angov E, Stewart VA, Lyon JA DGH Jr, Withers MR: Blood stage malaria vaccine eliciting high antigen-specific antibody concentrations confers no protection to young children in Western Kenya. / PLoS One 2009, 4:e4708. CrossRef
4. Sagara I, Dicko A, Ellis RD, Fay MP, Diawara SI, Assadou MH, Sissoko MS, Kone M, Diallo AI, Saye R, Guindo MA, Kante O, Niambele MB, Miura K, Mullen GE, Pierce M, Martin LB, Dolo A, Diallo DA, Doumbo OK, Miller LH, Saul A: A randomized controlled phase 2 trial of the blood stage AMA1-C1/Alhydrogel malaria vaccine in children in Mali. / Vaccine 2009, 27:3090-098. CrossRef
5. Bouharoun-Tayoun H, Druilhe P: Plasmodium falciparum malaria: evidence for an isotype imbalance which may be responsible for delayed acquisition of protective immunity. / Infect Immun 1992, 60:1473-481.
6. Nebie I, Diarra A, Ouedraogo A, Soulama I, Bougouma EC, Tiono AB, Konate AT, Chilengi R, Theisen M, Dodoo D, Remarque E, Bosomprah S, Milligan P, Sirima SB: Humoral responses to Plasmodium falciparum blood-stage antigens and association with incidence of clinical malaria in children living in an area of seasonal malaria transmission in Burkina Faso, West Africa. / Infect Immun 2008, 76:759-66. CrossRef
7. Cowman AF, Crabb BS: Invasion of red blood cells by malaria parasites. / Cell 2006, 124:755-66. CrossRef
8. Theisen M, Vuust J, Gottschau A, Jepsen S, H?gh B: Antigenicity and immunogenicity of recombinant glutamate-rich protein of Plasmodium falciparum expressed in Escherichia coli . / Clin Diagn Lab Immunol 1995, 2:30-4.
9. McColl DJ, Anders RF: Conservation of structural motifs and antigenic diversity in the Plasmodium falciparum merozoite surface protein-3 (MSP-3). / Mol Biochem Parasitol 1997, 90:21-1. CrossRef
10. Theisen M, Soe S, Brunstedt K, Follmann F, Bredmose L, Israelsen H, Madsen S, Druilhe P: A Plasmodium falciparum GLURP–MSP3 chimeric protein; expression in Lactococcus lactis , immunogenicity and induction of biologically active antibodies. / Vaccine 2004, 9-0:1188-198. CrossRef
11. Esen M, Kremsner PG, Schleucher R, G?sslera M, Imoukhuedec EB, Imbaultc N, Leroyc O, Jepsene S, Knudsen BW, Schumm M, Knobloch J, Theisen M, Mordmüller B: Safety and immunogenicity of GMZ2 -a MSP3–GLURP fusion protein malaria vaccine candidate. / Vaccine 2009, 27:6862-868. CrossRef
12. Mordmüller B, Szywon K, Greutelaers B, Esen M, Mewono L, Treut C, Mürbeth RE, Chilengi R, Noor R, Kilama WL, Imoukhuede EB, Imbault N, Leroy O, Theisen M, Jepsen S, Milligan P, Fendel R, Kremsner PG, Issifou S: Safety and immunogenicity of the malaria vaccine candidate GMZ2 in malaria-exposed, adult individuals from Lambaréné Gabon. / Vaccine 2010, 28:6698-703. CrossRef
13. Federal democratic republic of Ethiopia ministry of health (FMoH): / National five-year strategic plan for malaria prevention and control in Ethiopia 2006-010. http://www.cdbph.org/documents
14. Zanini G, Soe S, Druilhe P, Theisen M, Muniz J, Daniel-Ribeiro C, Jr Oliveira S, Carvalho LJ, Alves FA, Bianco C: Immunization of Saimiri sciureus monkeys with a recombinant hybrid protein derived from the Plasmodium falciparum antigen glutamate-rich protein and merozoite surface protein 3 can induce partial protection with Freund and Montanide ISA720 adjuvants. / Clin Diagn Lab Immunol 2005, 12:242-48.
15. Druilhe P, Soe S, Theisen M, Roussilhon C, Khin-Saw A: Association between protection against clinical malaria and antibodies to merozoite surface antigens in an area of hyperendemicity in Myanmar: Complementarity between responses to merozoite surface protein 3 and the 220-kilodalton glutamate-rich protein. / Infect Immun 2004, 72:247-52. CrossRef
16. Baumann A, Magris M, Urbaez M-L, Vivas-Martinez S, Durán R, Nieves T, Esen M, Mordmüller B, Theisen M, Avilan L, Metzger W: Naturally acquired immune responses to malaria vaccine candidate antigens MSP3 and GLURP in Guahibo and Piaroa indigenous communities of the Venezuelan Amazon. / Malar J 2012, 11:46. CrossRef
17. Perraut R, Guillotte M, Drame I, Diouf B, Molez J, Tall A, Trape J, Mercereau-Puijalon O, Spiegel A, Garraud O: Evaluation of anti- Plasmodium falciparum antibodies in Senegalese adults using different types of crude extracts from various strains of parasite. / Microbes Infect 2002, 4:31-5. CrossRef
18. Wipasa J, Suphavilai C, Okell L, Cook J, Corran P, Thaikla K, Liewsaree W, Riley E, Hafalla J: Long-lived antibody and B cell memory responses to the human malaria parasites. Plasmodium falciparum and Plasmodium vivax . / PLoS Pathog 2010, 6:e1000770. CrossRef
19. Akpogheneta O, Duah N, Tetteh K, Dunyo S, Lanar D, Pinder M, Conway D: Duration of naturally acquired antibody responses to blood-stage Plasmodium falciparum is age dependent and antigen specific. / Infect Immun 2008, 76:1748-755. CrossRef
20. Metzger WG, Haywood M, Alessandro U, Drakeley C, Weiss H, Bojang K, Targett G, Greenwood B: Serological responses of Gambian children to immunization with the malaria vaccine SPf66. / Parasite Immunol 1999, 21:335-40. CrossRef
21. Courtin D, Oesterholt M, Huismans H, Kusi K, Milet J, Badaut C, Gaye O, Roeffen W, Remarque EJ, Sauerwein R, Garcia A, Luty AJF: The quantity and quality of African children’s IgG responses to merozoite surface antigens reflect protection to Plasmodium falciparum malaria. / PLoS One 2009, 4:e7590. CrossRef
22. Osier F, Fegan G, Polley S, Murungi L, Verra F, Tetteh K, Lowe B, Mwangi T, Bull PC, Thomas AW, Cavanagh DR, McBride JS, Lanar DE, Mackinnon MJ, Conway DJ, Marsh K: Breadth and magnitude of antibody responses to multiple Plasmodium falciparum merozoite antigens are associated with protection from clinical malaria. / Infect Immun 2008, 76:2240-248. CrossRef
23. Roussilhon C, Oeuvray C, Muller-Graf C, Tall A, Rogier C, Trape J-F, Theisen M, Balde A, Perignon JL, Druilhe P: Long-term clinical protection from falciparum malaria is strongly associated with IgG3 antibodies to merozoite surface protein 3. / PLoS Med 2007, 4:e320. CrossRef
24. Stanisic D, Richards J, McCallum F, Michon P, King C, Schoepflin S, Gilson P, Murphy V, Anders R, Mueller I, Beeson1 j: Immunoglobulin G subclass-specific responses against Plasmodium falciparum merozoite antigens are associated with control of parasitemia and protection from symptomatic illness. / Infect Immun 2009, 77:1165-174. CrossRef
25. Coffman RL, Lebman DA, Rothman P: Mechanism and regulation of immunoglobulin isotype switching. / Adv Immunol 1993, 54:229-70. CrossRef
26. Lane P, MacLennan I: Impaired IgG2 anti-pneumococcal antibody responses in patients with recurrent infection and normal IgG2 levels but no IgA. / Clin Exp Immunol 1986, 65:427-33.
27. Garraud O, Nkenfou C, Bradley J, Perler F, Nutman T: Identification of recombinant filarial proteins capable of inducing polyclonal and antigen‐specific IgE and IgG4 antibodies. / J Immunol 1995, 155:1316-325.
28. Yount W, Dorner M, Kunkel H, Kabat E: VI. Selective variation in subgroup composition and genetic markers. / J Exp Med 1968, 127:633-46. CrossRef
29. Dunne D, Grabowska A, Fulford A, Butterworth A, Sturrock R, Koech D, Ouma J: Human antibody response to Schistosoma mansoni : the influence of epitopes shared between different life-cycle stages on the response to the schistosomulum. / Eur J Immunol 1988, 18:123-31. CrossRef
30. Tongren J, Drakeley C, McDonald S, Reyburn HG, Manjurano A, Nkya WMM, Lemnge MM, Gowda CD, Todd JE, Corran PH, Riley EM: Target antigen, age and duration of antigen exposure independently regulate immunoglobulin G subclass switching in malaria. / Infect Immun 2006, 74:257-64. CrossRef
31. Aucan C, Traore Y, Tall F, Nacro B, Traore-Leroux T, Fumoux F, Riheit P: High immunoglobulin G2 (IgG2) and low IgG4 levels are associated with human resistance to Plasmodium falciparum malaria. / Infect Immun 2000, 68:1252-258. CrossRef
32. Segeja D, Mmbando B, Seth M, Lusingu JP, Lemnge M: Acquisition of antibodies to merozoite surface protein 3 among residents of Korogwe, north eastern Tanzania. / BMC Infect Dis 2010, 10:55. CrossRef
33. Metzeger W, Okenu D, David R, Cavanagh D, Robinson J, Bojang K, Weiss H, Mcbride J, Greenwood B, Conway D: Serum IgG3 to the Plasmodium falciparum merozoite surface protein 2 is strongly associated with a reduced prospective risk of malaria. / Parasite Immunol 2003, 25:307-12. CrossRef
34. Pratt-Riccio L, Lima-Junior J, Carvalho L, Theisen M, Espi’ndola-Mendes C, Santos F, Oliveira-Ferreira J, Goldberg A, Daniel-Ribeiro T, Banic D: Antibody response profiles induced by Plasmodium falciparum glutamate-rich protein in naturally exposed individuals from a Brazilian area endemic for malaria. / Am J Trop Med Hyg 2005, 73:1096.
35. Collins WE, Warren M, Skinner JC: Serological malaria survey in the Ethiopian highlands. / Am J Trop Med Hyg 1971, 20:199-05. - 作者单位：Hassen Mamo (1)
Meral Esen (2) (3)
Anthony Ajua (2) (3)
Michael Theisen (4) (5)
Benjamin Mordmüller (2) (3)
Beyene Petros (1)
1. Microbial, Cellular and Molecular Biology Department, College of Natural Sciences, Addis Ababa University, P. O. Box 1176, Addis Ababa, Ethiopia
2. Institute of Tropical Medicine, University of Tübingen, Wilhelmstra?e 27, Tübingen, 72074, Germany
3. Centre de Recherche Médicale de Lambaréné (CERMEL), Lambaréné, BP 118, Gabon
4. Department of Clinical Biochemistry and Immunology, Statens Serum Institut, Artillerivej 5, Copenhagen, S 2300, Denmark
5. Center for Medical Parasitology at Department of International Health, Immunology and Microbiology, University of Copenhagen, Bartholinsgade 2, Copenhagen, K 1356, Denmark
文摘
Background In Ethiopia, the general population is vulnerable to unpredictable epidemics of Plasmodium falciparum malaria. However, there is little information on the anti-malaria immune profile of the population in the endemic regions of the country. Methods The study was designed to investigate the nature of humoral immune response to malaria in two ethnic groups in two endemic localities: Shewa Robit in north, and Boditi in south Ethiopia which are characterized by varying levels of malaria transmission and altitude. In a cross-sectional study, the study participants were diagnosed for malaria infection microscopically and by the rapid diagnostic test (RDT). Sera were tested by using enzyme-linked immunosorbent assay (ELISA) for total immunoglobulin (Ig) G against P. falciparum blood-stage vaccine candidate GMZ2 and its subunits (Glutamate-rich protein (GLURP-R0), merozoite surface protein 3 (MSP3); as well as IgG subclasses against GLURP-R0 and MSP3. Results Whereas 23(8.6%) blood smear-positive cases for P. falciparum were detected in Boditi, all Shewa Robit study participants had no detectable P. falciparum infection. In both localities, total IgG prevalence and levels to GMZ2 were significantly higher than the response to the component domains indicating the strong recognition of GMZ2 by antibodies acquired through natural exposure. Total IgG and subclass prevalence and levels were higher in Shewa Robit than Boditi, suggesting difference in the intensity of malaria transmission in the two localities and/or genetic differences between the two populations in their response to the antigens. In both study sites, IgG subclass levels to GLURP-R0 were significantly higher than that to MSP3 for all corresponding subclasses in most individuals, indicating the higher relative antigenicity and probably protective potential of GLURP-R0 compared to MSP3. Against both GLURP-R0 and MSP3, the ratio of cytophilic to noncytophilic antibodies was >1 in the majority of the study participants, in both study sites, suggesting the induction of protective (cytophilic) antibodies against the two antigens. Analysis of age-related pattern in antibody levels against the antigens showed a positive association with increasing age. Conclusions P. falciparum GLURP-R0 and MSP3 separately as well as in a fused form in GMZ2 are readily recognized by the sera of the study populations. The significantly higher antibody prevalence and level detected against GMZ2 compared to either of its subunits separately, in naturally exposed populations, suggests the synergistic effect of GLURP-R0 and MSP3 and that GMZ2 could be a more relevant blood-stage malaria vaccine candidate than the individual components. Detection of high-level antibody responses in non-febrile, smear-negative individuals may possibly be an indication of a low-grade, asymptomatic sub-microscopic infection in the induction and maintenance of high-level malaria immunity.