Skip to main content
Top
Published in: Malaria Journal 1/2017

Open Access 01-12-2017 | Research

Antibody responses to two new Lactococcus lactis-produced recombinant Pfs48/45 and Pfs230 proteins increase with age in malaria patients living in the Central Region of Ghana

Authors: Festus K. Acquah, Evans K. Obboh, Kwame Asare, Johnson N. Boampong, Samuel Victor Nuvor, Susheel K. Singh, Michael Theisen, Kim C. Williamson, Linda Eva Amoah

Published in: Malaria Journal | Issue 1/2017

Login to get access

Abstract

Background

Recent advances in malaria control efforts have led to an increased number of national malaria control programmes implementing pre-elimination measures and demonstrated the need to develop new tools to track and control malaria transmission. Key to understanding transmission is monitoring the prevalence and immune response against the sexual stages of the parasite, known as gametocytes, which are responsible for transmission. Sexual-stage specific antigens, Pfs230 and Pfs48/45, have been identified and shown to be targets for transmission blocking antibodies, but they have been difficult to produce recombinantly in the absence of a fusion partner.

Methods

Regions of Pfs48/45 and Pfs230 known to contain transmission blocking epitopes, 6C and C0, respectively, were produced in a Lactococcus lactis expression system and used in enzyme linked immunosorbent assays to determine the seroreactivity of 95 malaria patients living in the Central Region of Ghana.

Results

Pfs48/45.6C and Pfs230.C0 were successfully produced in L. lactis in the absence of a fusion partner using a simplified purification scheme. Seroprevalence for L. lactis-produced Pfs48/45.6C and Pfs230.C0 in the study population was 74.7 and 72.8%, respectively.

Conclusions

A significant age-dependent increase in antibody titers was observed, which suggests a vaccine targeting these antigens could be boosted during a natural infection in the field.
Appendix
Available only for authorised users
Literature
1.
go back to reference WHO. World malaria report 2016. Geneva: World Health Organization; 2016. WHO. World malaria report 2016. Geneva: World Health Organization; 2016.
2.
go back to reference Kaslow DC. Transmission-blocking vaccines: uses and current status of development. Int J Parasitol. 1997;27:183–9.CrossRefPubMed Kaslow DC. Transmission-blocking vaccines: uses and current status of development. Int J Parasitol. 1997;27:183–9.CrossRefPubMed
3.
go back to reference Saeed M, Roeffen W, Alexander N, Drakeley CJ, Targett GA, Sutherland CJ. Plasmodium falciparum antigens on the surface of the gametocyte-infected erythrocyte. PLoS ONE. 2008;3:e2280.CrossRefPubMedPubMedCentral Saeed M, Roeffen W, Alexander N, Drakeley CJ, Targett GA, Sutherland CJ. Plasmodium falciparum antigens on the surface of the gametocyte-infected erythrocyte. PLoS ONE. 2008;3:e2280.CrossRefPubMedPubMedCentral
4.
go back to reference Carter R, Graves PM, Keister DB, Quakyi IA. Properties of epitopes of Pfs 48/45, a target of transmission blocking monoclonal antibodies, on gametes of different isolates of Plasmodium falciparum. Parasite Immunol. 1990;12:587–603.CrossRefPubMed Carter R, Graves PM, Keister DB, Quakyi IA. Properties of epitopes of Pfs 48/45, a target of transmission blocking monoclonal antibodies, on gametes of different isolates of Plasmodium falciparum. Parasite Immunol. 1990;12:587–603.CrossRefPubMed
5.
go back to reference Outchkourov N, Vermunt A, Jansen J, Kaan A, Roeffen W, Teelen K, et al. Epitope analysis of the malaria surface antigen pfs48/45 identifies a subdomain that elicits transmission blocking antibodies. J Biol Chem. 2007;282:17148–56.CrossRefPubMed Outchkourov N, Vermunt A, Jansen J, Kaan A, Roeffen W, Teelen K, et al. Epitope analysis of the malaria surface antigen pfs48/45 identifies a subdomain that elicits transmission blocking antibodies. J Biol Chem. 2007;282:17148–56.CrossRefPubMed
6.
go back to reference Read D, Lensen AH, Begarnie S, Haley S, Raza A, Carter R. Transmission-blocking antibodies against multiple, non-variant target epitopes of the Plasmodium falciparum gamete surface antigen Pfs230 are all complement-fixing. Parasite Immunol. 1994;16:511–9.CrossRefPubMed Read D, Lensen AH, Begarnie S, Haley S, Raza A, Carter R. Transmission-blocking antibodies against multiple, non-variant target epitopes of the Plasmodium falciparum gamete surface antigen Pfs230 are all complement-fixing. Parasite Immunol. 1994;16:511–9.CrossRefPubMed
7.
go back to reference Williamson KC, Keister DB, Muratova O, Kaslow DC. Recombinant Pfs230, a Plasmodium falciparum gametocyte protein, induces antisera that reduce the infectivity of Plasmodium falciparum to mosquitoes. Mol Biochem Parasitol. 1995;75:33–42.CrossRefPubMed Williamson KC, Keister DB, Muratova O, Kaslow DC. Recombinant Pfs230, a Plasmodium falciparum gametocyte protein, induces antisera that reduce the infectivity of Plasmodium falciparum to mosquitoes. Mol Biochem Parasitol. 1995;75:33–42.CrossRefPubMed
8.
go back to reference Ouedraogo AL, Roeffen W, Luty AJ, de Vlas SJ, Nebie I, Ilboudo-Sanogo E, et al. Naturally acquired immune responses to Plasmodium falciparum sexual stage antigens Pfs48/45 and Pfs230 in an area of seasonal transmission. Infect Immun. 2011;79:4957–64.CrossRefPubMedPubMedCentral Ouedraogo AL, Roeffen W, Luty AJ, de Vlas SJ, Nebie I, Ilboudo-Sanogo E, et al. Naturally acquired immune responses to Plasmodium falciparum sexual stage antigens Pfs48/45 and Pfs230 in an area of seasonal transmission. Infect Immun. 2011;79:4957–64.CrossRefPubMedPubMedCentral
9.
go back to reference Bousema JT, Drakeley CJ, Kihonda J, Hendriks JC, Akim NI, Roeffen W, et al. A longitudinal study of immune responses to Plasmodium falciparum sexual stage antigens in Tanzanian adults. Parasite Immunol. 2007;29:309–17.CrossRefPubMed Bousema JT, Drakeley CJ, Kihonda J, Hendriks JC, Akim NI, Roeffen W, et al. A longitudinal study of immune responses to Plasmodium falciparum sexual stage antigens in Tanzanian adults. Parasite Immunol. 2007;29:309–17.CrossRefPubMed
10.
go back to reference Bousema T, Roeffen W, Meijerink H, Mwerinde H, Mwakalinga S, van Gemert GJ, et al. The dynamics of naturally acquired immune responses to Plasmodium falciparum sexual stage antigens Pfs230 & Pfs48/45 in a low endemic area in Tanzania. PLoS ONE. 2010;5:e14114.CrossRefPubMedPubMedCentral Bousema T, Roeffen W, Meijerink H, Mwerinde H, Mwakalinga S, van Gemert GJ, et al. The dynamics of naturally acquired immune responses to Plasmodium falciparum sexual stage antigens Pfs230 & Pfs48/45 in a low endemic area in Tanzania. PLoS ONE. 2010;5:e14114.CrossRefPubMedPubMedCentral
11.
go back to reference Singh SK, Roeffen W, Andersen G, Bousema T, Christiansen M, Sauerwein R, et al. A Plasmodium falciparum 48/45 single epitope R0.6C subunit protein elicits high levels of transmission blocking antibodies. Vaccine. 2015;33:1981–6.CrossRefPubMed Singh SK, Roeffen W, Andersen G, Bousema T, Christiansen M, Sauerwein R, et al. A Plasmodium falciparum 48/45 single epitope R0.6C subunit protein elicits high levels of transmission blocking antibodies. Vaccine. 2015;33:1981–6.CrossRefPubMed
12.
go back to reference Roeffen W, Theisen M, van de Vegte-Bolmer M, van Gemert G, Arens T, Andersen G, et al. Transmission-blocking activity of antibodies to Plasmodium falciparum GLURP.10C chimeric protein formulated in different adjuvants. Malar J. 2015;14:443.CrossRefPubMedPubMedCentral Roeffen W, Theisen M, van de Vegte-Bolmer M, van Gemert G, Arens T, Andersen G, et al. Transmission-blocking activity of antibodies to Plasmodium falciparum GLURP.10C chimeric protein formulated in different adjuvants. Malar J. 2015;14:443.CrossRefPubMedPubMedCentral
13.
go back to reference Baldwin SL, Roeffen W, Singh SK, Tiendrebeogo RW, Christiansen M, Beebe E, et al. Synthetic TLR4 agonists enhance functional antibodies and CD4+ T-cell responses against the Plasmodium falciparum GMZ2. 6C multi-stage vaccine antigen. Vaccine. 2016;34:2207–15.CrossRefPubMed Baldwin SL, Roeffen W, Singh SK, Tiendrebeogo RW, Christiansen M, Beebe E, et al. Synthetic TLR4 agonists enhance functional antibodies and CD4+ T-cell responses against the Plasmodium falciparum GMZ2. 6C multi-stage vaccine antigen. Vaccine. 2016;34:2207–15.CrossRefPubMed
14.
go back to reference Outchkourov NS, Roeffen W, Kaan A, Jansen J, Luty A, Schuiffel D, et al. Correctly folded Pfs48/45 protein of Plasmodium falciparum elicits malaria transmission-blocking immunity in mice. Proc Natl Acad Sci USA. 2008;105:4301–5.CrossRefPubMedPubMedCentral Outchkourov NS, Roeffen W, Kaan A, Jansen J, Luty A, Schuiffel D, et al. Correctly folded Pfs48/45 protein of Plasmodium falciparum elicits malaria transmission-blocking immunity in mice. Proc Natl Acad Sci USA. 2008;105:4301–5.CrossRefPubMedPubMedCentral
15.
go back to reference Theisen M, Roeffen W, Singh SK, Andersen G, Amoah L, van de Vegte-Bolmer M, et al. A multi-stage malaria vaccine candidate targeting both transmission and asexual parasite life-cycle stages. Vaccine. 2014;32:2623–30.CrossRefPubMed Theisen M, Roeffen W, Singh SK, Andersen G, Amoah L, van de Vegte-Bolmer M, et al. A multi-stage malaria vaccine candidate targeting both transmission and asexual parasite life-cycle stages. Vaccine. 2014;32:2623–30.CrossRefPubMed
16.
go back to reference Kushwaha A, Rao PP, Suresh RP, Chauhan VS. Immunogenicity of recombinant fragments of Plasmodium falciparum acidic basic repeat antigen produced in Escherichia coli. Parasite Immunol. 2001;23:435–44.CrossRefPubMed Kushwaha A, Rao PP, Suresh RP, Chauhan VS. Immunogenicity of recombinant fragments of Plasmodium falciparum acidic basic repeat antigen produced in Escherichia coli. Parasite Immunol. 2001;23:435–44.CrossRefPubMed
17.
go back to reference Tachibana M, Wu Y, Iriko H, Muratova O, MacDonald NJ, Sattabongkot J, et al. N-terminal prodomain of Pfs230 synthesized using a cell-free system is sufficient to induce complement-dependent malaria transmission-blocking activity. Clin Vaccine Immunol. 2011;18:1343–50.CrossRefPubMedPubMedCentral Tachibana M, Wu Y, Iriko H, Muratova O, MacDonald NJ, Sattabongkot J, et al. N-terminal prodomain of Pfs230 synthesized using a cell-free system is sufficient to induce complement-dependent malaria transmission-blocking activity. Clin Vaccine Immunol. 2011;18:1343–50.CrossRefPubMedPubMedCentral
18.
go back to reference Farrance CE, Rhee A, Jones RM, Musiychuk K, Shamloul M, Sharma S, et al. A plant-produced Pfs230 vaccine candidate blocks transmission of Plasmodium falciparum. Clin Vaccine Immunol. 2011;18:1351–7.CrossRefPubMedPubMedCentral Farrance CE, Rhee A, Jones RM, Musiychuk K, Shamloul M, Sharma S, et al. A plant-produced Pfs230 vaccine candidate blocks transmission of Plasmodium falciparum. Clin Vaccine Immunol. 2011;18:1351–7.CrossRefPubMedPubMedCentral
19.
go back to reference Asare KK, Boampong JN, Afoakwah R, Ameyaw EO, Sehgal R, Quashie NB. Use of proscribed chloroquine is associated with an increased risk of pfcrt T76 mutation in some parts of Ghana. Malar J. 2014;13:246.CrossRefPubMedPubMedCentral Asare KK, Boampong JN, Afoakwah R, Ameyaw EO, Sehgal R, Quashie NB. Use of proscribed chloroquine is associated with an increased risk of pfcrt T76 mutation in some parts of Ghana. Malar J. 2014;13:246.CrossRefPubMedPubMedCentral
21.
go back to reference Williamson KC, Criscio MD, Kaslow DC. Cloning and expression of the gene for Plasmodium falciparum transmission-blocking target antigen, Pfs230. Mol Biochem Parasitol. 1993;58:355–8.CrossRefPubMed Williamson KC, Criscio MD, Kaslow DC. Cloning and expression of the gene for Plasmodium falciparum transmission-blocking target antigen, Pfs230. Mol Biochem Parasitol. 1993;58:355–8.CrossRefPubMed
22.
go back to reference Ravn P, Arnau J, Madsen SM, Vrang A, Israelsen H. Optimization of signal peptide SP310 for heterologous protein production in Lactococcus lactis. Microbiology. 2003;149:2193–201.CrossRefPubMed Ravn P, Arnau J, Madsen SM, Vrang A, Israelsen H. Optimization of signal peptide SP310 for heterologous protein production in Lactococcus lactis. Microbiology. 2003;149:2193–201.CrossRefPubMed
23.
go back to reference Holo H, Nes IF. Transformation of Lactococcus by electroporation. Electroporation Protoc Microorg. 1995;47:195–199.CrossRef Holo H, Nes IF. Transformation of Lactococcus by electroporation. Electroporation Protoc Microorg. 1995;47:195–199.CrossRef
24.
go back to reference Kapust RB, Tozser J, Fox JD, Anderson DE, Cherry S, Copeland TD, et al. Tobacco etch virus protease: mechanism of autolysis and rational design of stable mutants with wild-type catalytic proficiency. Protein Eng. 2001;14:993–1000.CrossRefPubMed Kapust RB, Tozser J, Fox JD, Anderson DE, Cherry S, Copeland TD, et al. Tobacco etch virus protease: mechanism of autolysis and rational design of stable mutants with wild-type catalytic proficiency. Protein Eng. 2001;14:993–1000.CrossRefPubMed
25.
go back to reference Baidjoe A, Stone W, Ploemen I, Shagari S, Grignard L, Osoti V, et al. Combined DNA extraction and antibody elution from filter papers for the assessment of malaria transmission intensity in epidemiological studies. Malar J. 2013;12:272.CrossRefPubMedPubMedCentral Baidjoe A, Stone W, Ploemen I, Shagari S, Grignard L, Osoti V, et al. Combined DNA extraction and antibody elution from filter papers for the assessment of malaria transmission intensity in epidemiological studies. Malar J. 2013;12:272.CrossRefPubMedPubMedCentral
26.
go back to reference Artimo P, Jonnalagedda M, Arnold K, Baratin D, Csardi G, de Castro E, et al. ExPASy: SIB bioinformatics resource portal. Nucleic Acids Res. 2012;40:W597–603.CrossRefPubMedPubMedCentral Artimo P, Jonnalagedda M, Arnold K, Baratin D, Csardi G, de Castro E, et al. ExPASy: SIB bioinformatics resource portal. Nucleic Acids Res. 2012;40:W597–603.CrossRefPubMedPubMedCentral
27.
go back to reference Price R, Nosten F, Simpson JA, Luxemburger C, Phaipun L, ter Kuile F, et al. Risk factors for gametocyte carriage in uncomplicated falciparum malaria. Am J Trop Med Hyg. 1999;60:1019–23.CrossRefPubMed Price R, Nosten F, Simpson JA, Luxemburger C, Phaipun L, ter Kuile F, et al. Risk factors for gametocyte carriage in uncomplicated falciparum malaria. Am J Trop Med Hyg. 1999;60:1019–23.CrossRefPubMed
28.
go back to reference Bousema T, Drakeley C. Epidemiology and infectivity of Plasmodium falciparum and Plasmodium vivax gametocytes in relation to malaria control and elimination. Clin Microbiol Rev. 2011;24:377–410.CrossRefPubMedPubMedCentral Bousema T, Drakeley C. Epidemiology and infectivity of Plasmodium falciparum and Plasmodium vivax gametocytes in relation to malaria control and elimination. Clin Microbiol Rev. 2011;24:377–410.CrossRefPubMedPubMedCentral
29.
go back to reference Neafsey DE, Juraska M, Bedford T, Benkeser D, Valim C, Griggs A, et al. Genetic diversity and protective efficacy of the RTS, S/AS01 malaria vaccine. N Engl J Med. 2015;373:2025–37.CrossRefPubMedPubMedCentral Neafsey DE, Juraska M, Bedford T, Benkeser D, Valim C, Griggs A, et al. Genetic diversity and protective efficacy of the RTS, S/AS01 malaria vaccine. N Engl J Med. 2015;373:2025–37.CrossRefPubMedPubMedCentral
30.
go back to reference Bustamante PJ, Woodruff DC, Oh J, Keister DB, Muratova O, Williamson KC. Differential ability of specific regions of Plasmodium falciparum sexual-stage antigen, Pfs230, to induce malaria transmission-blocking immunity. Parasite Immunol. 2000;22:373–80.CrossRefPubMed Bustamante PJ, Woodruff DC, Oh J, Keister DB, Muratova O, Williamson KC. Differential ability of specific regions of Plasmodium falciparum sexual-stage antigen, Pfs230, to induce malaria transmission-blocking immunity. Parasite Immunol. 2000;22:373–80.CrossRefPubMed
31.
go back to reference Ayanful-Torgby R, Oppong A, Abankwa J, Acquah F, Williamson KC, Amoah LE. Plasmodium falciparum genotype and gametocyte prevalence in children with uncomplicated malaria in coastal Ghana. Malar J. 2016;15:592.CrossRefPubMedPubMedCentral Ayanful-Torgby R, Oppong A, Abankwa J, Acquah F, Williamson KC, Amoah LE. Plasmodium falciparum genotype and gametocyte prevalence in children with uncomplicated malaria in coastal Ghana. Malar J. 2016;15:592.CrossRefPubMedPubMedCentral
32.
go back to reference Bousema JT, Roeffen W, van der Kolk M, de Vlas SJ, van de Vegte-Bolmer M, Bangs MJ, et al. Rapid onset of transmission-reducing antibodies in javanese migrants exposed to malaria in papua, indonesia. Am J Trop Med Hyg. 2006;74:425–31.PubMed Bousema JT, Roeffen W, van der Kolk M, de Vlas SJ, van de Vegte-Bolmer M, Bangs MJ, et al. Rapid onset of transmission-reducing antibodies in javanese migrants exposed to malaria in papua, indonesia. Am J Trop Med Hyg. 2006;74:425–31.PubMed
33.
go back to reference Jones S, Grignard L, Nebie I, Chilongola J, Dodoo D, Sauerwein R, et al. Naturally acquired antibody responses to recombinant Pfs230 and Pfs48/45 transmission blocking vaccine candidates. J Infect. 2015;71:117–27.CrossRefPubMed Jones S, Grignard L, Nebie I, Chilongola J, Dodoo D, Sauerwein R, et al. Naturally acquired antibody responses to recombinant Pfs230 and Pfs48/45 transmission blocking vaccine candidates. J Infect. 2015;71:117–27.CrossRefPubMed
34.
go back to reference Dinko B, King E, Targett GA, Sutherland CJ. Antibody responses to surface antigens of Plasmodium falciparum gametocyte-infected erythrocytes and their relation to gametocytaemia. Parasite Immunol. 2016;38:352–64.CrossRefPubMedPubMedCentral Dinko B, King E, Targett GA, Sutherland CJ. Antibody responses to surface antigens of Plasmodium falciparum gametocyte-infected erythrocytes and their relation to gametocytaemia. Parasite Immunol. 2016;38:352–64.CrossRefPubMedPubMedCentral
35.
go back to reference Niederwieser I, Felger I, Beck HP. Limited polymorphism in Plasmodium falciparum sexual-stage antigens. Am J Trop Med Hyg. 2001;64:9–11.CrossRefPubMed Niederwieser I, Felger I, Beck HP. Limited polymorphism in Plasmodium falciparum sexual-stage antigens. Am J Trop Med Hyg. 2001;64:9–11.CrossRefPubMed
36.
go back to reference Aurrecoechea C, Brestelli J, Brunk BP, Dommer J, Fischer S, Gajria B, et al. PlasmoDB: a functional genomic database for malaria parasites. Nucleic Acids Res. 2009;37:D539–43.CrossRefPubMed Aurrecoechea C, Brestelli J, Brunk BP, Dommer J, Fischer S, Gajria B, et al. PlasmoDB: a functional genomic database for malaria parasites. Nucleic Acids Res. 2009;37:D539–43.CrossRefPubMed
Metadata
Title
Antibody responses to two new Lactococcus lactis-produced recombinant Pfs48/45 and Pfs230 proteins increase with age in malaria patients living in the Central Region of Ghana
Authors
Festus K. Acquah
Evans K. Obboh
Kwame Asare
Johnson N. Boampong
Samuel Victor Nuvor
Susheel K. Singh
Michael Theisen
Kim C. Williamson
Linda Eva Amoah
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Malaria Journal / Issue 1/2017
Electronic ISSN: 1475-2875
DOI
https://doi.org/10.1186/s12936-017-1955-0

Other articles of this Issue 1/2017

Malaria Journal 1/2017 Go to the issue