Volume 76, Issue 6
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645


Naturally acquired antibodies to five variants of the merozoite surface protein 2 (MSP-2), a target of clinical immunity to malaria, were measured in a cohort of rural Amazonians. Local MSP-2 variants comprised both highly divergent families of alleles (FC27 and 3D7). Total IgG antibodies to two FC27-type antigens were found in 22–28% of subjects at baseline, with substantial cross-reactivity between variants and stable concentrations and specificities over time. The IgG antibodies to three 3D7-type antigens were less prevalent (6–7%), less cross-reactive, and short-lived; subsequent exposure to 3D7-type parasites rarely elicited homologous response. The clinical spectrum of 109 incident infections in our cohort ranged between asymptomatic infection and fully symptomatic but uncomplicated disease. Parasitemia at the time of diagnosis, rather than cumulative malaria exposure or acquired immunity (presence of variant-specific antibodies matching the MSP-2 type in infecting parasites), was a major predictor of perceived symptom severity.


Article metrics loading...

The graphs shown below represent data from March 2017
Loading full text...

Full text loading...



  1. Ferreira MU, da Silva-Nunes M, Wunderlich G, 2004. Antigenic diversity and immune evasion by malaria parasites. Clin Diagn Lab Immunol 11 : 987–995. [Google Scholar]
  2. Taylor RR, Allen SJ, Greenwood BM, Riley EM, 1998. IgG3 antibodies to Plasmodium falciparum merozoite surface protein 2 (MSP2): increasing prevalence with age and association with clinical immunity to malaria. Am J Trop Med Hyg 58 : 406–413. [Google Scholar]
  3. Metzger WG, Okenu DM, Cavanagh DR, Robinson JV, Bojang KA, Weiss HA, McBride JS, Greenwood BM, Conway DJ, 2003. Serum IgG3 to the Plasmodium falciparum merozoite surface protein 2 is strongly associated with a reduced prospective risk of malaria. Parasite Immunol 25 : 307–312. [Google Scholar]
  4. Polley SD, Conway DJ, Cavanagh DR, McBride JS, Lowe BS, Williams TN, Mwangi TW, Marsh K, 2006. High levels of serum antibodies to merozoite surface porotein 2 of Plasmodium falciparum are associated with reduced risk of clinical malaria in coastal Kenya. Vaccine 24 : 4233–4246. [Google Scholar]
  5. Snewin VA, Herrera MA, Sanchez G, Scherf A, Langsley G, Herrera S, 1991. Polymorphism of the alleles of the merozoite surface antigens MSA1 and MSA2 in Plasmodium falciparum wild isolates from Colombia. Mol Biochem Parasitol 49 : 265–276. [Google Scholar]
  6. Ferreira MU, Hartl DL, 2007. Plasmodium falciparum: worldwide sequence diversity and evolution of the malaria vaccine candidate merozoite surface protein-2 (MSP-2). Exp Parasitol 115 : 32–40. [Google Scholar]
  7. Al-Yaman F, Genton B, Anders RF, Falk M, Triglia T, Lewis D, Hii J, Beck H-P, Alpers MP, 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 : 593–602. [Google Scholar]
  8. Taylor RR, Smith DB, Robinson VJ, McBride JS, Riley EM, 1995. Human antibody response to Plasmodium falciparum merozoite surface protein 2 is serogroup specific and predominantly of the immunoglobulin G3 subclass. Infect Immun 63 : 4382–4388. [Google Scholar]
  9. Ekala MT, Jouin H, Lekoulou F, Mercereau-Puijalon O, Ntoumi F, 2002. Allelic-family specific humoral responses to merozoite surface protein 2 (MSP-2) in Gabonese residents with Plasmodium falciparum infections. Clin Exp Immunol 129 : 326–331. [Google Scholar]
  10. Felger I, Livingstone T, Beck H-P, 1993. Plasmodium falciparum: a rapid technique for genotyping the merozoite surface protein 2. Exp Parasitol 77 : 372–375. [Google Scholar]
  11. Kanunfre KA, Leoratti FM, Hoffmann EH, Durlacher RR, Ferreira AW, Moraes-Ávila SL, Ferreira MU, 2003. Differential recognition of Plasmodium falciparum merozoite surface protein 2 variants by antibodies from malaria patients in Brazil. Clin Diagn Lab Immunol 10 : 973–976. [Google Scholar]
  12. Flück C, Smith T, Beck H-P, Irion A, Betuela I, Alpers MP, Anders RF, Saul A, Genton B, Felger I, 2004. Strain-specific humoral response to a polymorphic malaria vaccine. Infect Immun 72 : 6300–6305. [Google Scholar]
  13. Tonon AP, Hoffmann EH, da Silveira LA, Ribeiro AG, Gonçalves CR, Ribolla PE, Wunderlich G, Ferreira MU, 2004. Plasmodium falciparum: sequence diversity and antibody recognition of the merozoite surface protein-2 (MSP-2) in Brazilian Amazonia. Exp Parasitol 108 : 114–125. [Google Scholar]
  14. Genton B, Betuela L, Felger I, Al-Yaman F, Anders RF, Saul A, Rare L, Baisor M, Lorry K, Brown GV, Pye D, Irving DO, Smith TA, Beck H-P, Alpers MP, 2002. A recombinant blood-stage malaria vaccine reduces Plasmodium falciparum density and exerts selective pressure on parasite populations in a phase 1–2b trial in Papua New Guinea. J Infect Dis 185 : 820–827. [Google Scholar]
  15. Bull PC, Lowe BS, Kortok M, Molyneaux CS, Newbold CI, Marsh K, 1998. Parasite antigens on the infected red cell surface are targets of naturally acquired immunity to malaria. Nat Med 4 : 358–360. [Google Scholar]
  16. Bull PC, Marsh K, 2002. The role of antibodies to Plasmodium falciparum-infected-erythrocyte surface antigens in naturally acquired immunity to malaria. Trends Microbiol 10 : 55–58. [Google Scholar]
  17. da Silva-Nunes M, Malafronte RS, Luz BA, Souza EA, Martins LC, Rodrigues SG, Chiang JO, Vasconcelos PF, Muniz PT, Ferreira MU, 2006. The Acre Project: the epidemiology of malaria and arthropod-borne vírus infections in a rural Amazonian population. Cad Saúde Publica 22 : 1325–1334. [Google Scholar]
  18. Trape J-F, 1985. Rapid evaluation of malaria parasite density and standardization of thick smear examination for epidemiological investigations. Trans R Soc Trop Med Hyg 79 : 181–184. [Google Scholar]
  19. Kimura M, Kaneko O, Liu Q, Zhou M, Kawamoto F, Wataya Y, Otani S, Yamaguchi Y, Tanabe K, 1997. Identification of the four species of human malaria parasites by nested PCR that targets variant sequences in the small subunit rRNA gene. Parasitol Int 46 : 91–95. [Google Scholar]
  20. Win TT, Lin K, Mizuno S, Zhou M, Liu Q, Ferreira MU, Tantular IS, Kojima S, Ishii A, Kawamoto F, 2002. Wide distribution of Plasmodium ovale in Myanmar. Trop Med Int Health 7 : 231–239. [Google Scholar]
  21. Cavasini MT, Ribeiro WL, Kawamoto F, Ferreira MU, 2000. How prevalent is Plasmodium malariae in Rondônia, western Brazilian Amazon? Rev Soc Bras Med Trop 33 : 489–492. [Google Scholar]
  22. Scopel KK, Fontes CJ, Nunes AC, Horta MF, Braga EM, 2004. Low sensitivity of nested PCR using Plasmodium DNA extracted from stained thick blood smears: an epidemiological retrospective study among subjects with low parasitaemia in an endemic area of the Brazilian Amazon region. Malaria J 3 : 8. [Google Scholar]
  23. Karunaweera ND, Carter R, Grau GE, Mendis K, 1998. Demonstration of anti-disease immunity to Plasmodium vivax malaria in Sri Lanka using a quantitative method to assess clinical disease. Am J Trop Med Hyg 58 : 204–210. [Google Scholar]
  24. World Health Organization, 2000. Severe falciparum malaria. Trans R Soc Trop Med Hyg 94 (Suppl. 1) : S1–S90. [Google Scholar]
  25. Felger I, Irion A, Steiger S, Beck H-P, 1999. Epidemiology of multiple Plasmodium falciparum infections. 2. Genotypes of merozoite surface protein 2 of Plasmodium falciparum in Tanzania. Trans R Soc Trop Med Hyg 93 (Suppl) : 3–9. [Google Scholar]
  26. Tonhosolo R, Wunderlich G, Ferreira MU, 2001. Differential antibody recognition of four allelic variants of the merozoite surface protein-2 (MSP-2) of Plasmodium falciparum. J Eukaryot Microbiol 48 : 556–564. [Google Scholar]
  27. Scopel KK, Fontes CJ, Ferreira MU, Braga EM, 2006. Factors associated with immunoglobulin G subclass polarization in naturally acquired antibodies to Plasmodium falciparum merozoite surface proteins: a cross-sectional survey in Brazilian Amazonia. Clin Vaccine Immunol 13 : 810–813. [Google Scholar]
  28. Weisman S, Wang L, Billman-Jacobe H, Nham DH, Richie TL, Coppel RL, 2001. Antibody responses to infections with strains of Plasmodium falciparum expressing diverse forms of merozoite surface protein-2. Infect Immun 69 : 959–967. [Google Scholar]
  29. Felger I, Steiger S, Hatz C, Smith T, Beck H-P, 2003. Antigenic cross-reactivity between different alleles of the Plasmodium falciparum merozoite surface protein 2. Parasite Immunol 25 : 531–543. [Google Scholar]
  30. Franks S, Baton L, Tetteh K, Tongren E, Dewin D, Akanmori BD, Koram KA, Ranford-Cartwright LC, Riley EM, 2003. Genetic diversity and antigenic polymorphism in Plasmodium falciparum: extensive serological cross-reactivity between allelic variants of merozoite surface protein 2. Infect Immun 71 : 3485–3495. [Google Scholar]
  31. Taylor RR, Egan A, McGuiness D, Jepson A, Adair R, Drakeley C, Riley E, 1996. Selective recognition of malaria antigens by human serum antibodies is not genetically determined but demonstrates some features of clonal imprinting. Int Immunol 8 : 905–915. [Google Scholar]
  32. Engelbracht F, Felger I, Genton B, Alpers M, Beck H-P, 1995. Plasmodium falciparum: malaria morbidity is associated with specific merozoite surface protein 2 genotypes. Exp Parasitol 81 : 90–96. [Google Scholar]
  33. Sallenave-Sales S, Ferreira-da-Cruz MF, Faria CP, Cerruti C Jr, Daniel-Ribeiro CT, Zalis MG, 2003. Plasmodium falciparum: limited genetic diversity of MSP-2 in isolates circulating in Brazilian endemic areas. Exp Parasitol 103 : 127–135. [Google Scholar]
  34. Mond JJ, Lees A, Snapper CM, 1995. T-cell independent antigens type 2. Annu Rev Immunol 13 : 655–692. [Google Scholar]
  35. Alves FP, Durlacher RR, Menezes MJ, Krieger H, Pereira da Silva LH, Camargo EP, 2002. High prevalence of asymptomatic Plasmodium vivax and Plasmodium falciparum infections in native Amazonian populations. Am J Trop Med Hyg 66 : 641–648. [Google Scholar]

Data & Media loading...

  • Received : 22 Dec 2006
  • Accepted : 05 Mar 2007

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error