Dynamics of Polymorphism in a Malaria Vaccine Antigen at a Vaccine-testing Site in Mali

Overview

Journal PLoS Med

Specialty General Medicine

Date 2007 Mar 16

PMID 17355170

Citations 58

Authors

Shannon L Takala

Drissa Coulibaly

Mahamadou A Thera

Alassane Dicko

David L Smith

Ando B Guindo

Abdoulaye K Kone

Karim Traore

Amed Ouattara

Abdoulaye A Djimde

Paul S Sehdev

Kirsten E Lyke

Dapa A Diallo

Ogobara K Doumbo

Christopher V Plowe

Affiliations

Soon will be listed here.

Abstract

Background: Malaria vaccines based on the 19-kDa region of merozoite surface protein 1 (MSP-1(19)) derived from the 3D7 strain of Plasmodium falciparum are being tested in clinical trials in Africa. Knowledge of the distribution and natural dynamics of vaccine antigen polymorphisms in populations in which malaria vaccines will be tested will guide vaccine design and permit distinction between natural fluctuations in genetic diversity and vaccine-induced selection.

Methods And Findings: Using pyrosequencing, six single-nucleotide polymorphisms in the nucleotide sequence encoding MSP-1(19) were genotyped from 1,363 malaria infections experienced by 100 children who participated in a prospective cohort study in Mali from 1999 to 2001. The frequencies of 14 MSP-1(19) haplotypes were compared over the course of the malaria transmission season for all three years, in three age groups, and in consecutive infections within individuals. While the frequency of individual MSP-1(19) haplotypes fluctuated, haplotypes corresponding to FVO and FUP strains of P. falciparum (MSP-1(19) haplotypes QKSNGL and EKSNGL, respectively) were most prevalent during three consecutive years and in all age groups with overall prevalences of 46% (95% confidence interval [CI] 44%-49%) and 36% (95% CI 34%-39%), respectively. The 3D7 haplotype had a lower overall prevalence of 16% (95% CI 14%-18%). Multiplicity of infection based on MSP-1(19) was higher at the beginning of the transmission season and in the oldest individuals (aged > or =11 y). Three MSP-1(19) haplotypes had a reduced frequency in symptomatic infections compared to asymptomatic infections. Analyses of the dynamics of MSP-1(19) polymorphisms in consecutive infections implicate three polymorphisms (at positions 1691, 1700, and 1701) as being particularly important in determining allele specificity of anti-MSP-1(19) immunity.

Conclusions: Parasites with MSP-1(19) haplotypes different from that of the leading vaccine strain were consistently the most prevalent at a vaccine trial site. If immunity elicited by an MSP-1-based vaccine is allele-specific, a vaccine based on either the FVO or FUP strain might have better initial efficacy at this site. This study, to our knowledge the largest of its kind to date, provides molecular information needed to interpret population responses to MSP-1-based vaccines and suggests that certain MSP-1(19) polymorphisms may be relevant to cross-protective immunity.

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References

Thera M, Doumbo O, Coulibaly D, Diallo D, Sagara I, Dicko A . Safety and allele-specific immunogenicity of a malaria vaccine in Malian adults: results of a phase I randomized trial. PLoS Clin Trials. 2006; 1(7):e34. PMC: 1851722. DOI: 10.1371/journal.pctr.0010034. View

Branch O, Oloo A, Nahlen B, Kaslow D, Lal A . Anti-merozoite surface protein-1 19-kDa IgG in mother-infant pairs naturally exposed to Plasmodium falciparum: subclass analysis with age, exposure to asexual parasitemia, and protection against malaria. V. The Asembo Bay Cohort Project. J Infect Dis. 2000; 181(5):1746-52. DOI: 10.1086/315424. View

Coulibaly D, Diallo D, Thera M, Dicko A, Guindo A, Kone A . Impact of preseason treatment on incidence of falciparum malaria and parasite density at a site for testing malaria vaccines in Bandiagara, Mali. Am J Trop Med Hyg. 2003; 67(6):604-10. DOI: 10.4269/ajtmh.2002.67.604. View

Hughes A . Positive selection and interallelic recombination at the merozoite surface antigen-1 (MSA-1) locus of Plasmodium falciparum. Mol Biol Evol. 1992; 9(3):381-93. DOI: 10.1093/oxfordjournals.molbev.a040730. View

MILLER L, Roberts T, Shahabuddin M, McCutchan T . Analysis of sequence diversity in the Plasmodium falciparum merozoite surface protein-1 (MSP-1). Mol Biochem Parasitol. 1993; 59(1):1-14. DOI: 10.1016/0166-6851(93)90002-f. View

Greenwood B, Mutabingwa T . Malaria in 2002. Nature. 2002; 415(6872):670-2. DOI: 10.1038/415670a. View

Obaro S, Adegbola R, Banya W, Greenwood B . Carriage of pneumococci after pneumococcal vaccination. Lancet. 1996; 348(9022):271-2. DOI: 10.1016/s0140-6736(05)65585-7. View

Gonzalez B, Hulten K, Lamberth L, Kaplan S, Mason Jr E . Streptococcus pneumoniae serogroups 15 and 33: an increasing cause of pneumococcal infections in children in the United States after the introduction of the pneumococcal 7-valent conjugate vaccine. Pediatr Infect Dis J. 2006; 25(4):301-5. DOI: 10.1097/01.inf.0000207484.52850.38. View

Angov E, Aufiero B, Turgeon A, Van Handenhove M, Ockenhouse C, Kester K . Development and pre-clinical analysis of a Plasmodium falciparum Merozoite Surface Protein-1(42) malaria vaccine. Mol Biochem Parasitol. 2003; 128(2):195-204. DOI: 10.1016/s0166-6851(03)00077-x. View

10.

Riley E, Allen S, Wheeler J, Blackman M, Bennett S, TAKACS B . 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. 1992; 14(3):321-37. DOI: 10.1111/j.1365-3024.1992.tb00471.x. View

11.

Alloueche A, Milligan P, Conway D, Pinder M, Bojang K, Doherty T . Protective efficacy of the RTS,S/AS02 Plasmodium falciparum malaria vaccine is not strain specific. Am J Trop Med Hyg. 2003; 68(1):97-101. View

12.

Lal R, Chakrabarti S, Yang C . Impact of genetic diversity of HIV-1 on diagnosis, antiretroviral therapy & vaccine development. Indian J Med Res. 2005; 121(4):287-314. View

13.

Dagan R, Givon-Lavi N, Zamir O, Fraser D . Effect of a nonavalent conjugate vaccine on carriage of antibiotic-resistant Streptococcus pneumoniae in day-care centers. Pediatr Infect Dis J. 2003; 22(6):532-40. DOI: 10.1097/01.inf.0000069761.11093.c3. View

14.

Ferreira M, Ribeiro W, Tonon A, Kawamoto F, Rich S . Sequence diversity and evolution of the malaria vaccine candidate merozoite surface protein-1 (MSP-1) of Plasmodium falciparum. Gene. 2003; 304:65-75. DOI: 10.1016/s0378-1119(02)01180-0. View

15.

Ockenhouse C, Angov E, Kester K, Diggs C, Soisson L, Cummings J . Phase I safety and immunogenicity trial of FMP1/AS02A, a Plasmodium falciparum MSP-1 asexual blood stage vaccine. Vaccine. 2005; 24(15):3009-17. DOI: 10.1016/j.vaccine.2005.11.028. View

16.

Conway D, Cavanagh D, Tanabe K, Roper C, Mikes Z, Sakihama N . A principal target of human immunity to malaria identified by molecular population genetic and immunological analyses. Nat Med. 2000; 6(6):689-92. DOI: 10.1038/76272. View

17.

Diallo T, Spiegel A, Diouf A, Perraut R, Kaslow D, Garraud O . Short report: IgG1/IgG3 antibody responses to various analogs of recombinant ypfmsp119--a study in immune adults living in areas of Plasmodium falciparum transmission. Am J Trop Med Hyg. 2001; 64(3-4):204-6. DOI: 10.4269/ajtmh.2001.64.204. View

18.

Qari S, Shi Y, Goldman I, Nahlen B, Tibayrenc M, Lal A . Predicted and observed alleles of Plasmodium falciparum merozoite surface protein-1 (MSP-1), a potential malaria vaccine antigen. Mol Biochem Parasitol. 1998; 92(2):241-52. DOI: 10.1016/s0166-6851(98)00010-3. View

19.

Gerdil C . The annual production cycle for influenza vaccine. Vaccine. 2003; 21(16):1776-9. DOI: 10.1016/s0264-410x(03)00071-9. View

20.

John C, ODonnell R, Sumba P, Moormann A, de Koning-Ward T, King C . Evidence that invasion-inhibitory antibodies specific for the 19-kDa fragment of merozoite surface protein-1 (MSP-1 19) can play a protective role against blood-stage Plasmodium falciparum infection in individuals in a malaria endemic area of Africa. J Immunol. 2004; 173(1):666-72. DOI: 10.4049/jimmunol.173.1.666. View