336
Views
0
CrossRef citations to date
0
Altmetric
REVIEW

Humoral Immune Responses to P. falciparum Circumsporozoite Protein (Pfcsp) Induced by the RTS, S Vaccine – Current Update

ORCID Icon
Pages 2147-2157 | Received 13 Dec 2022, Accepted 23 Mar 2023, Published online: 12 Apr 2023

References

  • World Health Organization. World malaria report 2022. Available from: https://www.who.int/teams/global-malaria-programme/reports/world-malaria-report-2022. Accessed April 9, 2023.
  • Manescu P, Shaw MJ, Elmi M, et al. Expert-level automated malaria diagnosis on routine blood films with deep neural networks. Am J Hematol. 2020;95(8):883–891. doi:10.1002/AJH.25827
  • Laurens MB. RTS,S/AS01 vaccine (MosquirixTM): an overview. Hum Vaccin Immunother. 2020;16(3):480–489. doi:10.1080/21645515.2019.1669415
  • Elimination T malERA RCP on T for M. malERA: an updated research agenda for diagnostics, drugs, vaccines, and vector control in malaria elimination and eradication. PLOS Med. 2017;14(11):e1002455. doi:10.1371/JOURNAL.PMED.1002455
  • Peterson I, Kapito-Tembo A, Bauleni A, et al. Overdiagnosis of malaria illness in an endemic setting: a facility-based surveillance study in Malawi. Am J Trop Med Hyg. 2021;104(6):2123–2130. doi:10.4269/ajtmh.20-1209
  • Scally SW, Murugan R, Bosch A, et al. Rare PfCSP C-terminal antibodies induced by live sporozoite vaccination are ineffective against malaria infection. J Exp Med. 2018;215(1):63–75. doi:10.1084/JEM.20170869
  • Cha S-J, Kim M-S, Na CH, Jacobs-Lorena M. Plasmodium sporozoite phospholipid scramblase interacts with mammalian carbamoyl-phosphate synthetase 1 to infect hepatocytes. Nat Commun. 2021;12(1). doi:10.1038/S41467-021-27109-7
  • Langowski MD, Khan FA, Savransky S, et al. Restricted valency (NPNA)n repeats and junctional epitope-based circumsporozoite protein vaccines against Plasmodium falciparum. Npj Vaccines. 2022;7(1):13. doi:10.1038/S41541-022-00430-Y
  • Uyar Y, Akşit A, Karaca S, Ceylan ŞS, Yürük M. 37 NANP ve 4 NVDP Epitoplu Plasmodium falciparum Rekombinant Circumsporozoite Proteinin Ekspresyonu ve Moleküler Karakterizasyonu [Production and molecular characterization of Plasmodium falciparum recombinant circumsporozoite protein with 37 NANP and 4 NVDP epitopes]. Mikrobiyol Bul. 2017;51(1):41–51. Turkish. doi:10.5578/mb.46549
  • RTS, S Clinical Trials Partnership. A Phase 3 trial of RTS,S/AS01 malaria vaccine in African Infants. N Engl J Med. 2012;367(24):2284–2295. doi:10.1056/NEJMOA1208394
  • First Results of Phase. A Phase 3 trial of RTS,S/AS01 malaria vaccine in African Children. N Engl J Med. 2011;365(20):1863–1875. doi:10.1056/nejmoa1102287
  • Malaria: phase 3 trial results for vaccine RTS,S/AS01. Available from: https://www.who.int/news-room/questions-and-answers/item/phase-3-trial-results-for-malaria-vaccine-rtss-as01. Accessed November 21, 2022.
  • Zhang YL, Pan WQ. The world’s first malaria vaccine: hope and challenge. Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi. 2022;33(6):560–562. doi:10.16250/j.32.1374.2021283
  • Arora N, Anbalagan L, Pannu AK. Towards eradication of malaria: is the WHO’s RTS,S/AS01 vaccination effective enough? Risk Manag Healthc Policy. 2021;14:1033–1039. doi:10.2147/RMHP.S219294
  • Kurtovic L, Wetzel D, Reiling L, et al. Novel virus-like particle vaccine encoding the circumsporozoite protein of plasmodium falciparum is immunogenic and induces functional antibody responses in mice. Front Immunol. 2021;12. doi:10.3389/FIMMU.2021.641421
  • McCann RS, Kabaghe AN, Moraga P, et al. The effect of community-driven larval source management and house improvement on malaria transmission when added to the standard malaria control strategies in Malawi: a cluster-randomized controlled trial. Malar J. 2021;20(1). doi:10.1186/s12936-021-03769-0
  • Vareta J, Buchwald AG, Barrall A, et al. Submicroscopic malaria infection is not associated with fever in cross-sectional studies in Malawi. Malar J. 2020;19(1). doi:10.1186/s12936-020-03296-4
  • Oseno B, Marura F, Ogwang R, et al. Characterization of Anopheles gambiae D7 salivary proteins as markers of human–mosquito bite contact. Parasit Vectors. 2022;15(1). doi:10.1186/s13071-021-05130-5
  • Wahl I, Wardemann H. How to induce protective humoral immunity against Plasmodium falciparum circumsporozoite protein. J Exp Med. 2022;219(2). doi:10.1084/jem.20201313
  • Reiling L, Boyle MJ, White MT, et al. Targets of complement-fixing antibodies in protective immunity against malaria in children. Nat Commun. 2019;10(1). doi:10.1038/s41467-019-08528-z
  • Leitner WW, Haraway M, Pierson T, Bergmann-Leitner ES. Role of opsonophagocytosis in immune protection against malaria. Vaccines. 2020;8(2):264. doi:10.3390/vaccines8020264
  • Langowski MD, Khan FA, Bitzer AA, et al. Optimization of a Plasmodium falciparum circumsporozoite protein repeat vaccine using the tobacco mosaic virus platform. Proc Natl Acad Sci U S A. 2020;117(6):3114–3122. doi:10.1073/pnas.1911792117
  • Kisalu NK, Idris AH, Weidle C, et al. A human monoclonal antibody prevents malaria infection by targeting a new site of vulnerability on the parasite. Nat Med. 2018;24(4):408–416. doi:10.1038/nm.4512
  • Jelínková L, Jhun H, Eaton A, Petrovsky N, Zavala F, Chackerian B. An epitope-based malaria vaccine targeting the junctional region of circumsporozoite protein. Npj Vaccines. 2021;6(1). doi:10.1038/S41541-020-00274-4
  • Francica JR, Shi W, Chuang GY, et al. Design of alphavirus virus-like particles presenting circumsporozoite junctional epitopes that elicit protection against malaria. Vaccines. 2021;9(3):272. doi:10.3390/VACCINES9030272
  • Herrera R, Anderson C, Kumar K, et al. Reversible conformational change in the plasmodium falciparum circumsporozoite protein masks Its adhesion domains. Infect Immun. 2015;83(10):3771–3780. doi:10.1128/IAI.02676-14
  • PATH’s malaria vaccine initiative. Available from: https://www.malariavaccine.org/files/content/page/files/RTSS.FAQs_FINAL.pdf. Accessed February 4, 2023.
  • de Almeida MEM, Alves KCS, de Vasconcelos MGS, et al. Bacillus subtilis spores as delivery system for nasal Plasmodium falciparum circumsporozoite surface protein immunization in a murine model. Sci Rep. 2022;12(1):1–8. doi:10.1038/s41598-022-05344-2
  • Wang LT, Hurlburt NK, Schön A, et al. The light chain of the L9 antibody is critical for binding circumsporozoite protein minor repeats and preventing malaria. Cell Rep. 2022;38(7):110367. doi:10.1016/j.celrep.2022.110367
  • White NJ. Determinants of relapse periodicity in Plasmodium vivax malaria. Malar J. 2011;10(1):297. doi:10.1186/1475-2875-10-297
  • Calvo-Calle JM, Mitchell R, Altszuler R, Othoro C, Nardin E. Identification of a neutralizing epitope within minor repeat region of Plasmodium falciparum CS protein. Npj Vaccines. 2021;6(1):1–8. doi:10.1038/s41541-020-00272-6
  • McNamara HA, Idris AH, Sutton HJ, et al. Antibody feedback limits the expansion of B cell responses to malaria vaccination but drives diversification of the humoral response. Cell Host Microbe. 2020;28(4):572–585.e7. doi:10.1016/j.chom.2020.07.001
  • McCall MBB, Kremsner PG, Mordmüller B. Correlating efficacy and immunogenicity in malaria vaccine trials. Semin Immunol. 2018;39:52–64. doi:10.1016/j.smim.2018.08.002
  • Jensen AR, Adams Y, Hviid L. Cerebral Plasmodium falciparum malaria: the role of PfEMP1 in its pathogenesis and immunity, and PfEMP1-based vaccines to prevent it. Immunol Rev. 2020;293(1):230–252. doi:10.1111/imr.12807
  • Suscovich TJ, Fallon JK, Das J, et al. Mapping functional humoral correlates of protection against malaria challenge following RTS,S/AS01 vaccination. Sci Transl Med. 2020;12(553). doi:10.1126/SCITRANSLMED.ABB4757
  • Feng G, Wines BD, Kurtovic L, et al. Mechanisms and targets of Fcγ-receptor mediated immunity to malaria sporozoites. Nat Commun. 2021;12(1). doi:10.1038/S41467-021-21998-4
  • Kurtovic L, Atre T, Feng G, et al. Multifunctional antibodies are induced by the RTS,S malaria vaccine and associated with protection in a phase 1/2a trial. J Infect Dis. 2021;224(7):1128–1138. doi:10.1093/INFDIS/JIAA144
  • Garcia-Senosiain A, Kana IH, Singh S, et al. Neutrophils dominate in opsonic phagocytosis of P. falciparum blood-stage merozoites and protect against febrile malaria. Commun Biol. 2021;4(1). doi:10.1038/S42003-021-02511-5
  • Opi DH, Kurtovic L, Chan JA, Horton JL, Feng G, Beeson JG. Multi-functional antibody profiling for malaria vaccine development and evaluation. Expert Rev Vaccines. 2021;20(10):1257–1272. doi:10.1080/14760584.2021.1981864
  • Mugo RM, Mwai K, Mwacharo J, et al. Seven-year kinetics of RTS, S/AS01-induced anti-CSP antibodies in young Kenyan children. Malar J. 2021;20(1):1–8. doi:10.1186/s12936-021-03961-2
  • Bejon P, Lusingu J, Olotu A, et al. Efficacy of RTS,S/AS01E vaccine against malaria in children 5 to 17 months of age. N Engl J Med. 2008;359(24):2521. doi:10.1056/NEJMOA0807381
  • Olotu A, Fegan G, Wambua J, et al. Four-year efficacy of RTS,S/AS01E and its interaction with malaria exposure. N Engl J Med. 2013;368(12):1111–1120. doi:10.1056/NEJMOA1207564/SUPPL_FILE/NEJMOA1207564_DISCLOSURES.PDF
  • Tan J, Cho H, Pholcharee T, et al. Functional human IgA targets a conserved site on malaria sporozoites. Sci Transl Med. 2021;13(599). doi:10.1126/scitranslmed.abg2344
  • Gaudinski MR, Berkowitz NM, Idris AH, et al. A monoclonal antibody for malaria prevention. N Engl J Med. 2021;385(9):803–814. doi:10.1056/NEJMOA2034031
  • Kurtovic L, Drew DR, Dent AE, Kazura JW, Beeson JG. Antibody targets and properties for complement-fixation against the circumsporozoite protein in malaria immunity. Front Immunol. 2021;12:1–12. doi:10.3389/fimmu.2021.775659
  • Bergmann-Leitner ES, Scheiblhofer S, Weiss R, et al. C3d binding to the circumsporozoite protein carboxy-terminus deviates immunity against malaria. Int Immunol. 2005;17(3):245–255. doi:10.1093/INTIMM/DXH205
  • Schofield L, Uadia P. Lack of Ir gene control in the immune response to malaria. I. A thymus-independent antibody response to the repetitive surface protein of sporozoites. J Immunol. 1990;144(7):2781–2788. doi:10.4049/jimmunol.144.7.2781
  • Goundis D, Reid KBM. Properdin, the terminal complement components, thrombospondin and the circumsporozoite protein of malaria parasites contain similar sequence motifs. Nature. 1988;335(6185):82–85. doi:10.1038/335082A0
  • Meraldi V, Audran R, Romero JF, et al. OM-174, a new adjuvant with a potential for human use, induces a protective response when administered with the synthetic C-terminal fragment 242-310 from the circumsporozoite protein of Plasmodium berghei. Vaccine. 2003;21(19–20):2485–2491. doi:10.1016/S0264-410X(03)00093-8
  • Pholcharee T, Oyen D, Flores-Garcia Y, et al. Structural and biophysical correlation of anti-NANP antibodies with in vivo protection against P. falciparum. Nat Commun. 2021;12(1). doi:10.1038/s41467-021-21221-4
  • Thai E, Costa G, Weyrich A, et al. A high-affinity antibody against the CSP N-terminal domain lacks Plasmodium falciparum inhibitory activity. J Exp Med. 2020;217(11). doi:10.1084/JEM.20200061
  • Flores-Garcia Y, Wang LT, Park M, et al. The P. falciparum CSP repeat region contains three distinct epitopes required for protection by antibodies in vivo. PLoS Pathog. 2021;17(11):1–15. doi:10.1371/journal.ppat.1010042
  • Chaudhury S, MacGill RS, Early AM, et al. Breadth of humoral immune responses to the C-terminus of the circumsporozoite protein is associated with protective efficacy induced by the RTS,S malaria vaccine. Vaccine. 2021;39(6):968–975. doi:10.1016/J.VACCINE.2020.12.055
  • Irani V, Guy AJ, Andrew D, Beeson JG, Ramsland PA, Richards JS. Molecular properties of human IgG subclasses and their implications for designing therapeutic monoclonal antibodies against infectious diseases. Mol Immunol. 2015;67(2Pt A):171–182. doi:10.1016/J.MOLIMM.2015.03.255
  • Ubillos I, Ayestaran A, Nhabomba AJ, et al. Baseline exposure, antibody subclass, and hepatitis B response differentially affect malaria protective immunity following RTS,S/AS01E vaccination in African children. BMC Med. 2018;16(1). doi:10.1186/S12916-018-1186-4
  • Kurtovic L, Behet MC, Feng G, et al. Human antibodies activate complement against Plasmodium falciparum sporozoites, and are associated with protection against malaria in children. BMC Med. 2018;16(1). doi:10.1186/S12916-018-1054-2
  • Stanisic DI, Fowkes FJI, Koinari M, et al. Acquisition of antibodies against Plasmodium falciparum merozoites and malaria immunity in young children and the influence of age, force of infection, and magnitude of response. Infect Immun. 2015;83(2):646–660. doi:10.1128/IAI.02398-14
  • Diebolder CA, Beurskens FJ, De Jong RN, et al. Complement is activated by IgG hexamers assembled at the cell surface. Science. 2014;343(6176):1260–1263. doi:10.1126/SCIENCE.1248943
  • Cragg MS, Morgan SM, Chan HTC, et al. Complement-mediated lysis by anti-CD20 mAb correlates with segregation into lipid rafts. Blood. 2003;101(3):1045–1052. doi:10.1182/BLOOD-2002-06-1761
  • Teeling JL, Mackus WJM, Wiegman LJJM, et al. The biological activity of human CD20 monoclonal antibodies is linked to unique epitopes on CD20. J Immunol. 2006;177(1):362–371. doi:10.4049/JIMMUNOL.177.1.362
  • Chaudhury S, Ockenhouse CF, Regules JA, et al. The biological function of antibodies induced by the RTS,S/AS01 malaria vaccine candidate is determined by their fine specificity. Malar J. 2016;15(1):1–12. doi:10.1186/S12936-016-1348-9/FIGURES/8
  • Kester KE, McKinney DA, Tornieporth N, et al. A phase I/IIa safety, immunogenicity, and efficacy bridging randomized study of a two-dose regimen of liquid and lyophilized formulations of the candidate malaria vaccine RTS,S/AS02A in malaria-naïve adults. Vaccine. 2007;25(29):5359–5366. doi:10.1016/J.VACCINE.2007.05.005
  • Kester KE, Cummings JF, Ofori-Anyinam O, et al. Randomized, double-blind, phase 2a trial of falciparum malaria vaccines RTS,S/AS01B and RTS,S/AS02A in malaria-naive adults: safety, efficacy, and immunologic associates of protection. J Infect Dis. 2009;200(3):337–346. doi:10.1086/600120
  • Alonso PL, Sacarlal J, Aponte JJ, et al. Efficacy of the RTS,S/AS02A vaccine against Plasmodium falciparum infection and disease in young African children: randomised controlled trial. Lancet. 2004;364(9443):1411–1420. doi:10.1016/S0140-6736(04)17223-1
  • Agnandji ST, Lell B, Fernandes JF, et al. Efficacy and safety of the RTS,S/AS01 malaria vaccine during 18 months after vaccination: a phase 3 randomized, controlled trial in children and young infants at 11 African sites. PLOS Med. 2014;11(7):e1001685. doi:10.1371/JOURNAL.PMED.1001685
  • Hollingdale MR, Nardin EH, Tharavanij S, Schwartz AL, Nussenzweig RS. Inhibition of entry of Plasmodium falciparum and P. vivax sporozoites into cultured cells; an in vitro assay of protective antibodies. J Immunol. 1984;132(2):909–913. doi:10.4049/jimmunol.132.2.909
  • Chatterjee S, Wery M, Sharma P. A conserved peptide sequence of the Plasmodium falciparum circumsporozoite protein and antipeptide antibodies inhibit Plasmodium berghei sporozoite invasion of Hep-G2 cells and protect immunized mice against P. berghei sporozoite challenge. Infect Immun. 1995;63(11). doi:10.1128/IAI.63.11.4375-4381.1995
  • Rathore D, Nagarkatti R, Jani D, et al. An immunologically cryptic epitope of Plasmodium falciparum circumsporozoite protein facilitates liver cell recognition and induces protective antibodies that block liver cell invasion. J Biol Chem. 2005;280(21):20524–20529. doi:10.1074/JBC.M414254200
  • Oyen D, Torres JL, Wille-Reece U, et al. Structural basis for antibody recognition of the NANP repeats in Plasmodium falciparum circumsporozoite protein. Proc Natl Acad Sci U S A. 2017;114(48):E10438–E10445. doi:10.1073/PNAS.1715812114
  • Beeson JG, Kurtovic L, Dobaño C, et al. Challenges and strategies for developing efficacious and long-lasting malaria vaccines. Sci Transl Med. 2019;11(474). doi:10.1126/SCITRANSLMED.AAU1458
  • Kurtovic L, Agius PA, Feng G, et al. Induction and decay of functional complement-fixing antibodies by the RTS,S malaria vaccine in children, and a negative impact of malaria exposure. BMC Med. 2019;17(1). doi:10.1186/S12916-019-1277-X
  • Kester KE, McKinney DA, Tornieporth N, et al. Efficacy of recombinant circumsporozoite protein vaccine regimens against experimental Plasmodium falciparum malaria. J Infect Dis. 2001;183(4):640–647. doi:10.1086/318534
  • Stoute JA, Slaoui M, Heppner DG, et al.; RTS,S Malaria Vaccine Evaluation Group. A preliminary evaluation of a recombinant circumsporozoite protein vaccine against Plasmodium falciparum malaria. N Engl J Med. 1997;336(2):86–91. doi:10.1056/NEJM199701093360202
  • Illingworth J, Butler NS, Roetynck S, et al. Chronic exposure to Plasmodium falciparum is associated with phenotypic evidence of B and T cell exhaustion. J Immunol. 2013;190(3):1038–1047. doi:10.4049/JIMMUNOL.1202438
  • Chandramohan D, Zongo I, Sagara I, et al. Seasonal malaria vaccination with or without seasonal malaria chemoprevention. N Engl J Med. 2021;385(11):1005–1017. doi:10.1056/NEJMOA2026330
  • Nielsen CM, Vekemans J, Lievens M, Kester KE, Regules JA, Ockenhouse CF. RTS,S malaria vaccine efficacy and immunogenicity during Plasmodium falciparum challenge is associated with HLA genotype. Vaccine. 2018;36(12):1637–1642. doi:10.1016/J.VACCINE.2018.01.069
  • Portugal S, Pierce SK, Crompton PD. Young lives lost as B cells falter: what we are learning about antibody responses in malaria. J Immunol. 2013;190(7):3039–3046. doi:10.4049/JIMMUNOL.1203067
  • Scherf A, Lopez-Rubio JJ, Riviere L. Antigenic variation in Plasmodium falciparum. Annu Rev Microbiol. 2008;62:445–470. doi:10.1146/ANNUREV.MICRO.61.080706.093134
  • Takala SL, Plowe CV. Genetic diversity and malaria vaccine design, testing and efficacy: preventing and overcoming “vaccine resistant malaria”. Parasite Immunol. 2009;31(9):560–573. doi:10.1111/J.1365-3024.2009.01138.X
  • Urban BC, Hien TT, Day NP, et al. Fatal Plasmodium falciparum malaria causes specific patterns of splenic architectural disorganization. Infect Immun. 2005;73(4):1986–1994. doi:10.1128/IAI.73.4.1986-1994.2005
  • Ibison F, Olotu A, Muema DM, et al. Lack of avidity maturation of merozoite antigen-specific antibodies with increasing exposure to Plasmodium falciparum amongst children and adults exposed to endemic malaria in Kenya. PLoS One. 2012;7(12):e52939. doi:10.1371/JOURNAL.PONE.0052939
  • Weill JC, Weller S, Reynaud CA. Human marginal zone B cells. Annu Rev Immunol. 2009;27:267–285. doi:10.1146/ANNUREV.IMMUNOL.021908.132607
  • Weiss GE, Crompton PD, Li S, et al. Atypical memory B cells are greatly expanded in individuals living in a malaria-endemic area. J Immunol. 2009;183(3):2176–2182. doi:10.4049/JIMMUNOL.0901297
  • Asito AS, Moormann AM, Kiprotich C, Ng’ang’A ZW, Ploutz-Snyder R, Rochford R. Alterations on peripheral B cell subsets following an acute uncomplicated clinical malaria infection in children. Malar J. 2008;7. doi:10.1186/1475-2875-7-238
  • Butler NS, Moebius J, Pewe LL, et al. Therapeutic blockade of PD-L1 and LAG-3 rapidly clears established blood-stage Plasmodium infection. Nat Immunol. 2011;13(2):188–195. doi:10.1038/ni.2180
  • Donati D, Mok B, Chêne A, et al. Increased B cell survival and preferential activation of the memory compartment by a malaria polyclonal B cell activator. J Immunol. 2006;177(5):3035–3044. doi:10.4049/JIMMUNOL.177.5.3035
  • Nduati E, Gwela A, Karanja H, et al. The plasma concentration of the B cell activating factor is increased in children with acute malaria. J Infect Dis. 2011;204(6):962–970. doi:10.1093/INFDIS/JIR438
  • Traore B, Koné Y, Doumbo S, et al. The TLR9 agonist CpG fails to enhance the acquisition of Plasmodium falciparum-specific memory B cells in semi-immune adults in Mali. Vaccine. 2009;27(52):7299–7303. doi:10.1016/J.VACCINE.2009.08.023
  • Daniel-Ribeiro CT, Zanini G. Autoimmunity and malaria: what are they doing together? Acta Trop. 2000;76(3):205–221. doi:10.1016/S0001-706X(00)00099-1