Analysis of a Multi-component Multi-stage Malaria Vaccine Candidate--Tackling the Cocktail Challenge

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2015 Jul 7

PMID 26147206

Citations 23

Authors

Alexander Boes

Holger Spiegel

Nadja Voepel

Gueven Edgue

Veronique Beiss

Stephanie Kapelski

Rolf Fendel

Matthias Scheuermayer

Gabriele Pradel

Judith M Bolscher

Marije C Behet

Koen J Dechering

Cornelus C Hermsen

Robert W Sauerwein

Stefan Schillberg

Andreas Reimann

Rainer Fischer

Affiliations

Soon will be listed here.

Abstract

Combining key antigens from the different stages of the P. falciparum life cycle in the context of a multi-stage-specific cocktail offers a promising approach towards the development of a malaria vaccine ideally capable of preventing initial infection, the clinical manifestation as well as the transmission of the disease. To investigate the potential of such an approach we combined proteins and domains (11 in total) from the pre-erythrocytic, blood and sexual stages of P. falciparum into a cocktail of four different components recombinantly produced in plants. After immunization of rabbits we determined the domain-specific antibody titers as well as component-specific antibody concentrations and correlated them with stage specific in vitro efficacy. Using purified rabbit immune IgG we observed strong inhibition in functional in vitro assays addressing the pre-erythrocytic (up to 80%), blood (up to 90%) and sexual parasite stages (100%). Based on the component-specific antibody concentrations we calculated the IC50 values for the pre-erythrocytic stage (17-25 μg/ml), the blood stage (40-60 μg/ml) and the sexual stage (1.75 μg/ml). While the results underline the feasibility of a multi-stage vaccine cocktail, the analysis of component-specific efficacy indicates significant differences in IC50 requirements for stage-specific antibody concentrations providing valuable insights into this complex scenario and will thereby improve future approaches towards malaria vaccine cocktail development regarding the selection of suitable antigens and the ratios of components, to fine tune overall and stage-specific efficacy.

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References

Gantt S, Persson C, Rose K, Birkett A, Abagyan R, NUSSENZWEIG V . Antibodies against thrombospondin-related anonymous protein do not inhibit Plasmodium sporozoite infectivity in vivo. Infect Immun. 2000; 68(6):3667-73. PMC: 97657. DOI: 10.1128/IAI.68.6.3667-3673.2000. View

Farrance C, Rhee A, Mark Jones R, Musiychuk K, Shamloul M, Sharma S . A plant-produced Pfs230 vaccine candidate blocks transmission of Plasmodium falciparum. Clin Vaccine Immunol. 2011; 18(8):1351-7. PMC: 3147341. DOI: 10.1128/CVI.05105-11. View

Doolan D, Hoffman S . DNA-based vaccines against malaria: status and promise of the Multi-Stage Malaria DNA Vaccine Operation. Int J Parasitol. 2001; 31(8):753-62. DOI: 10.1016/s0020-7519(01)00184-9. View

Dutta S, Lalitha P, Ware L, Barbosa A, Moch J, Vassell M . Purification, characterization, and immunogenicity of the refolded ectodomain of the Plasmodium falciparum apical membrane antigen 1 expressed in Escherichia coli. Infect Immun. 2002; 70(6):3101-10. PMC: 127972. DOI: 10.1128/IAI.70.6.3101-3110.2002. View

Tachibana M, Wu Y, Iriko H, Muratova O, Macdonald N, Sattabongkot J . 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(8):1343-50. PMC: 3147338. DOI: 10.1128/CVI.05104-11. View

Hill A . Vaccines against malaria. Philos Trans R Soc Lond B Biol Sci. 2011; 366(1579):2806-14. PMC: 3146776. DOI: 10.1098/rstb.2011.0091. View

Kumar S, Collins W, Egan A, Yadava A, Garraud O, Blackman M . Immunogenicity and efficacy in aotus monkeys of four recombinant Plasmodium falciparum vaccines in multiple adjuvant formulations based on the 19-kilodalton C terminus of merozoite surface protein 1. Infect Immun. 2000; 68(4):2215-23. PMC: 97406. DOI: 10.1128/IAI.68.4.2215-2223.2000. View

Agnandji S, Lell B, Soulanoudjingar S, Fernandes J, Abossolo B, Conzelmann C . First results of phase 3 trial of RTS,S/AS01 malaria vaccine in African children. N Engl J Med. 2011; 365(20):1863-75. DOI: 10.1056/NEJMoa1102287. View

Gregory J, Li F, Tomosada L, Cox C, Topol A, Vinetz J . Algae-produced Pfs25 elicits antibodies that inhibit malaria transmission. PLoS One. 2012; 7(5):e37179. PMC: 3353897. DOI: 10.1371/journal.pone.0037179. View

10.

Alaro J, Angov E, Lopez A, Zhou H, Long C, Burns Jr J . Evaluation of the immunogenicity and vaccine potential of recombinant Plasmodium falciparum merozoite surface protein 8. Infect Immun. 2012; 80(7):2473-84. PMC: 3416454. DOI: 10.1128/IAI.00211-12. View

11.

Faber B, Younis S, Remarque E, Rodriguez Garcia R, Riasat V, Walraven V . Diversity covering AMA1-MSP119 fusion proteins as malaria vaccines. Infect Immun. 2013; 81(5):1479-90. PMC: 3648017. DOI: 10.1128/IAI.01267-12. View

12.

Fischer R, Schillberg S, Buyel J, Twyman R . Commercial aspects of pharmaceutical protein production in plants. Curr Pharm Des. 2013; 19(31):5471-7. DOI: 10.2174/1381612811319310002. View

13.

Seder R, Chang L, Enama M, Zephir K, Sarwar U, Gordon I . Protection against malaria by intravenous immunization with a nonreplicating sporozoite vaccine. Science. 2013; 341(6152):1359-65. DOI: 10.1126/science.1241800. View

14.

Mark Jones R, Chichester J, Mett V, Jaje J, Tottey S, Manceva S . A plant-produced Pfs25 VLP malaria vaccine candidate induces persistent transmission blocking antibodies against Plasmodium falciparum in immunized mice. PLoS One. 2013; 8(11):e79538. PMC: 3832600. DOI: 10.1371/journal.pone.0079538. View

15.

Feller T, Thom P, Koch N, Spiegel H, Addai-Mensah O, Fischer R . Plant-based production of recombinant Plasmodium surface protein pf38 and evaluation of its potential as a vaccine candidate. PLoS One. 2013; 8(11):e79920. PMC: 3836784. DOI: 10.1371/journal.pone.0079920. View

16.

Behet M, Foquet L, van Gemert G, Bijker E, Meuleman P, Leroux-Roels G . Sporozoite immunization of human volunteers under chemoprophylaxis induces functional antibodies against pre-erythrocytic stages of Plasmodium falciparum. Malar J. 2014; 13:136. PMC: 4113136. DOI: 10.1186/1475-2875-13-136. View

17.

Voepel N, Boes A, Edgue G, Beiss V, Kapelski S, Reimann A . Malaria vaccine candidate antigen targeting the pre-erythrocytic stage of Plasmodium falciparum produced at high level in plants. Biotechnol J. 2014; 9(11):1435-45. DOI: 10.1002/biot.201400350. View

18.

Kapelski S, Klockenbring T, Fischer R, Barth S, Fendel R . Assessment of the neutrophilic antibody-dependent respiratory burst (ADRB) response to Plasmodium falciparum. J Leukoc Biol. 2014; 96(6):1131-42. PMC: 4226792. DOI: 10.1189/jlb.4A0614-283RR. View

19.

Boes A, Spiegel H, Edgue G, Kapelski S, Scheuermayer M, Fendel R . Detailed functional characterization of glycosylated and nonglycosylated variants of malaria vaccine candidate PfAMA1 produced in Nicotiana benthamiana and analysis of growth inhibitory responses in rabbits. Plant Biotechnol J. 2014; 13(2):222-34. DOI: 10.1111/pbi.12255. View

20.

Kapelski S, Boes A, Spiegel H, de Almeida M, Klockenbring T, Reimann A . Fast track antibody V-gene rescue, recombinant expression in plants and characterization of a PfMSP4-specific antibody. Malar J. 2015; 14:50. PMC: 4323031. DOI: 10.1186/s12936-015-0577-7. View