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Gene Review

SERA-5  -  serine repeat antigen 5 (SERA-5)

Plasmodium falciparum 3D7

 
 
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Disease relevance of PFB0340c

  • None of the five rechallenged monkeys that had originally received SERA 1 and Freund's developed a countable parasitemia [1].
  • cDNA encoding the serine repeat antigen (SERA) (also called p126) of Plasmodium falciparum has been isolated from the FCR3 strain and inserted into a recombinant vaccinia virus designated vP870 [2].
  • Coimmunization of mice with SERA plasmid DNA and a plasmid expressing the hepatitis B surface antigen (pCMV-s) by the i.m. route resulted in higher anti-SERA titers than those generated in mice immunized with the SERA DNA plasmid alone [3].
  • We expressed two regions of the serine repeat antigen (SERA) protein of Plasmodium falciparum in Escherichia coli by synthesizing the genes with a changed codon usage [4].
  • Induction and displacement of an helix in the 6725 SERA peptide analogue confers protection against P. falciparum malaria [5].
 

High impact information on PFB0340c

  • In this paper, the expression and functional relevance of these eight genes and of a ninth SERA homologue found on chromosome 9 were examined in blood stage parasites [6].
  • Serine repeat antigen (SERA5) is predominantly expressed among the SERA multigene family of Plasmodium falciparum, and the acquired antibody titers correlate with serum inhibition of the parasite growth [7].
  • The unusual concentration of 27 serines in the COOH-terminal portion of the protein shares homology with a similar polyserine repeat of the serine repeat antigen (SERA protein) of Plasmodium falciparum [8].
  • Some immune sera that inhibit erythrocyte invasion by merozoites also agglutinate the merozoites as they emerge from rupturing schizonts [9].
  • The response of 9 clones to the various sera is presented, together with the DNA sequence encoding the epitopes [10].
 

Chemical compound and disease context of PFB0340c

  • Monkeys vaccinated with either SERA 1 and Freund's, SERA 1 and MF75.2, or MF75.2 alone and that had been challenged but did not develop a countable parasitemia were treated with a curative dose of mefloquine 100 days after parasite challenge and then rechallenged 40 days later [1].
 

Biological context of PFB0340c

  • Parsimony of reconciliation and a second criterion--implied mutational pattern at two key active sites in the SERA proteins-were also seen to be useful supplements to standard "bootstrap" analysis for inferred topologies [11].
  • To clarify the relationships among the numerous P. falciparum SERAs and to identify orthologs to SERA5 and SERA6 in Plasmodium species affecting rodents, gene trees were inferred from nucleotide and amino acid sequence data for 33 putative SERA homologs in seven different species [11].
  • The serine repeat antigen (SERA) gene family phylogeny in Plasmodium: the impact of GC content and reconciliation of gene and species trees [11].
  • We compared the immune responses induced in mice immunized with SERA-expressing plasmid DNA vaccines delivered by intramuscular (i.m.) injection or delivered intradermally by Gene Gun immunization [3].
  • Minimal antibody responses were detected following DNA vaccination with the N-terminal domain of SERA, suggesting that the N-terminal domain alone is not highly immunogenic by this route of vaccine delivery [3].
 

Anatomical context of PFB0340c

  • These observations suggest that the SE47'-specific antibodies inhibit parasite growth by cross-linking SERA molecules that are associated with merozoites in rupturing schizonts with partly broken RBC and parasitophorous vacuole membranes, blocking merozoite release [12].
  • Pooled sera from inhabitants of a malaria-endemic area reacted with epitopes in this region of the molecule, and four mouse monoclonal antibodies to this region also reacted with the native CS protein on sporozoites [13].
  • The sera from mice immunized with the four-plasmid formulation specifically recognized sporozoites, blood stage schizonts and gametes, indicating that DNA immunization induced antibody responses relevant to the native conformation [14].
  • Expression analysis of vP870-infected Vero cells by immunoprecipitation has demonstrated several intracellular forms of SERA and a single secreted SERA peptide [2].
  • We have established an in vitro cell-free system using a baculovirus-expressed recombinant SERA (bvSERA) that mimics the SERA processing that occurs in parasitized erythrocytes [15].
 

Associations of PFB0340c with chemical compounds

  • The Plasmodium falciparum serine repeat antigen (SERA) and serine repeat protein homologue (SERPH) contain highly conserved domains that appear to encode cysteine proteases or related proteins [16].
  • The characteristic polyserine sequence found in SERA was not present in any of the deduced V-SERA sequences [17].
  • Polytuftsin alone proved to be a very poor immunogen in our studies, since no anti-tuftsin antibodies could be detected in the sera [18].
  • Sera from Alhydrogel + CPG 7909 groups displayed significantly higher antibody titers (P < 0.025) than their comparable Alhydrogel alone group [19].
  • Anti-malarial activity was observed in sera obtained from rabbits which received chloroquine, mefloquine, pyrimethamine and cycloguanil, but not in those which received 4-4' diacetyldiaminodiphenylsulphone (DADDS) [20].
 

Analytical, diagnostic and therapeutic context of PFB0340c

  • The observed transmission-blocking activity of immune sera correlated with antibody levels measured by ELISA [21].
  • The anti-vP870 rabbit sera reacted with P. falciparum-infected erythrocytes by immunofluorescence analysis, recognized authentic SERA from schizonts by both immunoprecipitation and Western blot (immunoblot) analyses, and recognized proteolytically processed fragments of SERA secreted into the culture medium by Western blot analysis [2].
  • Vaccination with DNA may provide a viable alternative or may be used in conjunction with protein-based subunit vaccines to maximize the efficacy of a human malaria vaccine that includes immunogenic regions of the SERA protein [3].
  • Indirect-immunofluorescence assays with unfixed parasite cells showed that SE47'-specific immunoglobulin G (IgG) bound to SERA molecules on rupturing schizonts and merozoites but the IgG did not react with the schizont-infected erythrocytes (RBC) [12].
  • A control group that did not receive SERA 1 but only MF75.2 adjuvant was included [1].

References

  1. Protective immunity induced in Aotus monkeys by a recombinant SERA protein of Plasmodium falciparum: further studies using SERA 1 and MF75.2 adjuvant. Inselburg, J., Bathurst, I.C., Kansopon, J., Barr, P.J., Rossan, R. Infect. Immun. (1993) [Pubmed]
  2. Immunogenicity of the Plasmodium falciparum serine repeat antigen (p126) expressed by vaccinia virus. Tine, J.A., Conseil, V., Delplace, P., De Taisne, C., Camus, D., Paoletti, E. Infect. Immun. (1993) [Pubmed]
  3. Immune responses induced by gene gun or intramuscular injection of DNA vaccines that express immunogenic regions of the serine repeat antigen from Plasmodium falciparum. Belperron, A.A., Feltquate, D., Fox, B.A., Horii, T., Bzik, D.J. Infect. Immun. (1999) [Pubmed]
  4. Production of recombinant SERA proteins of Plasmodium falciparum in Escherichia coli by using synthetic genes. Sugiyama, T., Suzue, K., Okamoto, M., Inselburg, J., Tai, K., Horii, T. Vaccine (1996) [Pubmed]
  5. Induction and displacement of an helix in the 6725 SERA peptide analogue confers protection against P. falciparum malaria. Alba, M.P., Salazar, L.M., Purmova, J., Vanegas, M., Rodriguez, R., Patarroyo, M.E. Vaccine (2004) [Pubmed]
  6. A subset of Plasmodium falciparum SERA genes are expressed and appear to play an important role in the erythrocytic cycle. Miller, S.K., Good, R.T., Drew, D.R., Delorenzi, M., Sanders, P.R., Hodder, A.N., Speed, T.P., Cowman, A.F., de Koning-Ward, T.F., Crabb, B.S. J. Biol. Chem. (2002) [Pubmed]
  7. Serine repeat antigen (SERA5) is predominantly expressed among the SERA multigene family of Plasmodium falciparum, and the acquired antibody titers correlate with serum inhibition of the parasite growth. Aoki, S., Li, J., Itagaki, S., Okech, B.A., Egwang, T.G., Matsuoka, H., Palacpac, N.M., Mitamura, T., Horii, T. J. Biol. Chem. (2002) [Pubmed]
  8. Isolation and deduced amino acid sequence of the gene encoding gp115, a yeast glycophospholipid-anchored protein containing a serine-rich region. Vai, M., Gatti, E., Lacanà, E., Popolo, L., Alberghina, L. J. Biol. Chem. (1991) [Pubmed]
  9. Plasmodium falciparum antigens synthesized by schizonts and stabilized at the merozoite surface by antibodies when schizonts mature in the presence of growth inhibitory immune serum. Lyon, J.A., Haynes, J.D., Diggs, C.L., Chulay, J.D., Pratt-Rossiter, J.M. J. Immunol. (1986) [Pubmed]
  10. Characterisation of P. falciparum antigenic determinants isolated from a genomic expression library by differential antibody screening. Langsley, G., Scherf, A., Mercereau-Puijalon, O., Koenen, M., Kahane, B., Mattei, D., Guillotte, M., Sibilli, L., Garner, I., Müller-Hill, B. Nucleic Acids Res. (1985) [Pubmed]
  11. The serine repeat antigen (SERA) gene family phylogeny in Plasmodium: the impact of GC content and reconciliation of gene and species trees. Bourgon, R., Delorenzi, M., Sargeant, T., Hodder, A.N., Crabb, B.S., Speed, T.P. Mol. Biol. Evol. (2004) [Pubmed]
  12. Antibodies reactive with the N-terminal domain of Plasmodium falciparum serine repeat antigen inhibit cell proliferation by agglutinating merozoites and schizonts. Pang, X.L., Mitamura, T., Horii, T. Infect. Immun. (1999) [Pubmed]
  13. New B cell epitopes in the Plasmodium falciparum malaria circumsporozoite protein. Stüber, D., Bannwarth, W., Pink, J.R., Meloen, R.H., Matile, H. Eur. J. Immunol. (1990) [Pubmed]
  14. Multi-plasmid DNA vaccination avoids antigenic competition and enhances immunogenicity of a poorly immunogenic plasmid. Grifantini, R., Finco, O., Bartolini, E., Draghi, M., Del Giudice, G., Kocken, C., Thomas, A., Abrignani, S., Grandi, G. Eur. J. Immunol. (1998) [Pubmed]
  15. Characterization of proteases involved in the processing of Plasmodium falciparum serine repeat antigen (SERA). Li, J., Matsuoka, H., Mitamura, T., Horii, T. Mol. Biochem. Parasitol. (2002) [Pubmed]
  16. Humoral immune responses of Africans to cysteine protease-related antigens of Plasmodium falciparum. Gor, D.O., Rosenthal, P.J. J. Infect. Dis. (1998) [Pubmed]
  17. Identification and cloning of a locus of serine repeat antigen (sera)-related genes from Plasmodium vivax. Kiefer, M.C., Crawford, K.A., Boley, L.J., Landsberg, K.E., Gibson, H.L., Kaslow, D.C., Barr, P.J. Mol. Biochem. Parasitol. (1996) [Pubmed]
  18. Construction of a synthetic immunogen: use of the natural immunomodulator polytuftsin in malaria vaccines against RESA antigen of Plasmodium falciparum. Pawan, K., Ivanov, B.B., Kabilan, L., Rao, D.N. Vaccine (1994) [Pubmed]
  19. Enhancement of functional antibody responses to AMA1-C1/Alhydrogel, a Plasmodium falciparum malaria vaccine, with CpG oligodeoxynucleotide. Mullen, G.E., Giersing, B.K., Ajose-Popoola, O., Davis, H.L., Kothe, C., Zhou, H., Aebig, J., Dobrescu, G., Saul, A., Long, C.A. Vaccine (2006) [Pubmed]
  20. A rabbit--in vitro system to evaluate drug action against Plasmodium falciparum. Mrema, J.E., Rieckmann, K.H. Trans. R. Soc. Trop. Med. Hyg. (1983) [Pubmed]
  21. Long-lasting and transmission-blocking activity of antibodies to Plasmodium falciparum elicited in mice by protein conjugates of Pfs25. Kubler-Kielb, J., Majadly, F., Wu, Y., Narum, D.L., Guo, C., Miller, L.H., Shiloach, J., Robbins, J.B., Schneerson, R. Proc. Natl. Acad. Sci. U.S.A. (2007) [Pubmed]
 
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