Research advances on transmission-blocking vaccines targeting Plasmodium sexual stage

doi:10.12140/j.issn.1000-7423.2024.03.017

Abstract

Abstract:

Malaria remains a major global health challenge. At present, due to the application of drugs and related technologies, the burden of disease has been reduced to a certain extent, but morbidity and mortality remain very high. With the widespread emergence of drug resistance, it is urgent to explore and develop new anti-malarial strategies to effectively control and block the spread of malaria. The transmission-blocking vaccine (TBV), which targets the sexual stage, is a good option to control the transmission of Plasmodium from human hosts to mosquito vectors. The development of TBV has attracted attention domestically and internationally. It is considered to be one of the new technologies for malaria control. This article summarizes the research and development of TBV, as well as the discovery and progress of candidate antigens, and provides a theoretical reference for further research on TBV.

Key words: Malaria, Plasmodium, Transmission-blocking vaccine, Candidate antigen

CLC Number:

R531.3

WANG Rong, XU Jie, ZHU Xiaotong. Research advances on transmission-blocking vaccines targeting Plasmodium sexual stage[J]. CHINESE JOURNAL OF PARASITOLOGY AND PARASITIC DISEASES, 2024, 42(3): 399-406.

References 85

[1]	Ashour DS, Othman AA. Parasite-bacteria interrelationship[J]. Parasitol Res, 2020, 119(10): 3145-3164.
[2]	World Health Organization. World malaria report 2023 [EB/OL](2023-11-30) [2024-02-14]. https://wwwwhoint/publications/i/item/9789240086173
[3]	Feng J, Zhang L, Xia ZG, et al. Malaria elimination in China: an eminent milestone in the anti-malaria campaign and challenges in the post-elimination stage[J]. Chin J Parasitol Parasit Dis, 2021, 39(4): 421-428. (in Chinese)
	(丰俊, 张丽, 夏志贵, 等. 中国消除疟疾: 重要里程碑意义及消除后的挑战[J]. 中国寄生虫学与寄生虫病杂志, 2021, 39(4): 421-428.) doi: 10.12140/j.issn.1000-7423.2021.04.001
[4]	Zhang L, Yi BY, Yin JH, et al. Epidemiological characteristics of malaria in China, 2022[J]. Chin J Parasitol Parasit Dis, 2023, 41(2): 137-141. (in Chinese)
	(张丽, 易博禹, 尹建海, 等. 2022年全国疟疾疫情特征分析[J]. 中国寄生虫学与寄生虫病杂志, 2023, 41(2): 137-141.) doi: 10.12140/j.issn.1000-7423.2023.02.002
[5]	Moyes CL, Athinya DK, Seethaler T, et al. Evaluating insecticide resistance across African districts to aid malaria control decisions[J]. Proc Natl Acad Sci USA, 2020, 117(36): 22042-22050. doi: 10.1073/pnas.2006781117 pmid: 32843339
[6]	Stokes BH, Dhingra SK, Rubiano K, et al. Plasmodium falciparum K13 mutations in Africa and Asia impact artemisinin resistance and parasite fitness[J]. Elife, 2021, 10: e66277.
[7]	Richie TL, Saul A. Progress and challenges for malaria vaccines[J]. Nature, 2002, 415(6872): 694-701.
[8]	Bettencourt P. Current challenges in the identification of pre-erythrocytic malaria vaccine candidate antigens[J]. Front Immunol, 2020, 11:190. doi: 10.3389/fimmu.2020.00190 pmid: 32153565
[9]	Wang J, Zheng WQ, Liu F, et al. Characterization of Pb51 in Plasmodium berghei as a malaria vaccine candidate targeting both asexual erythrocytic proliferation and transmission[J]. Malar J, 2017, 16(1): 458.
[10]	Alves E, Salman AM, Leoratti F, et al. Evaluation of Plasmodium vivax cell-traversal protein for ookinetes and sporozoites as a preerythrocytic P. vivax vaccine[J]. Clin Vaccine Immunol, 2017, 24(4): e00501-e00516.
[11]	Miura K, Tachibana M, Takashima E, et al. Malaria transmission-blocking vaccines: wheat germ cell-free technology can accelerate vaccine development[J]. Expert Rev Vaccines, 2019, 18(10): 1017-1027. doi: 10.1080/14760584.2019.1674145 pmid: 31566026
[12]	Tsuboi T, Tachibana M, Kaneko O, et al. Transmission-blocking vaccine of vivax malaria[J]. Parasitol Int, 2003, 52(1): 1-11. pmid: 12543142
[13]	El-Moamly AA, El-Sweify MA. Malaria vaccines: the 60-year journey of hope and final success-lessons learned and future prospects[J]. Trop Med Health, 2023, 51(1): 29.
[14]	Guttery DS, Roques M, Holder AA, et al. Commit and transmit: molecular players in Plasmodium sexual development and zygote differentiation[J]. Trends Parasitol, 2015, 31(12): 676-685. doi: S1471-4922(15)00173-7 pmid: 26440790
[15]	Reece SE, Drew DR, Gardner A. Sex ratio adjustment and kin discrimination in malaria parasites[J]. Nature, 2008, 453(7195): 609-614.
[16]	Liu F, Yang F, Wang YR, et al. A conserved malaria parasite antigen Pb22 plays a critical role in male gametogenesis in Plasmodium berghei[J]. Cell Microbiol, 2021, 23(3): e13294.
[17]	Kou X, Zheng WQ, Du F, et al. Characterization of a Plasmodium berghei sexual stage antigen PbPH as a new candidate for malaria transmission-blocking vaccine[J]. Parasit Vectors, 2016, 9: 190. doi: 10.1186/s13071-016-1459-8 pmid: 27038925
[18]	Tachibana M, Ishino T, Takashima E, et al. A male gametocyte osmiophilic body and microgamete surface protein of the rodent malaria parasite Plasmodium yoelii (PyMiGS) plays a critical role in male osmiophilic body formation and exflagellation[J]. Cell Microbiol, 2018, 20(5): e12821.
[19]	Bansal GP, Weinstein CS, Kumar N. Insight into phagocytosis of mature sexual (gametocyte) stages of Plasmodium falciparum using a human monocyte cell line[J]. Acta Trop, 2016, 157: 96-101.
[20]	van Dijk MR, Janse CJ, Thompson J, et al. A central role for P48/45 in malaria parasite male gamete fertility[J]. Cell, 2001, 104(1): 153-164. pmid: 11163248
[21]	Eksi S, Czesny B, van Gemert GJ, et al. Malaria transmission-blocking antigen, Pfs230, mediates human red blood cell binding to exflagellating male parasites and oocyst production[J]. Mol Microbiol, 2006, 61(4): 991-998. pmid: 16879650
[22]	Chowdhury DR, Angov E, Kariuki T, et al. A potent malaria transmission blocking vaccine based on codon harmonized full length Pfs48/45 expressed in Escherichia coli[J]. PLoS One, 2009, 4(7): e6352.
[23]	Arredondo SA, Kappe SHI. The s48/45 six-cysteine proteins: mediators of interaction throughout the Plasmodium life cycle[J]. Int J Parasitol, 2017, 47(7): 409-423. doi: S0020-7519(16)30253-3 pmid: 27899328
[24]	Williamson KC, Criscio MD, Kaslow DC. Cloning and expression of the gene for Plasmodium falciparum transmission-blocking target antigen, Pfs230[J]. Mol Biochem Parasitol, 1993, 58(2): 355-358.
[25]	Molina-Cruz A, Canepa GE, Barillas-Mury C. Plasmodium P47: a key gene for malaria transmission by mosquito vectors[J]. Curr Opin Microbiol, 2017, 40: 168-174. doi: S1369-5274(17)30136-4 pmid: 29229188
[26]	Templeton TJ, Keister DB, Muratova O, et al. Adherence of erythrocytes during exflagellation of Plasmodium falciparum microgametes is dependent on erythrocyte surface sialic acid and glycophorins[J]. J Exp Med, 1998, 187(10): 1599-1609. doi: 10.1084/jem.187.10.1599 pmid: 9584138
[27]	Tao DY, Ubaida-Mohien C, Mathias DK, et al. Sex-partitioning of the Plasmodium falciparum stage V gametocyte proteome provides insight into falciparum-specific cell biology[J]. Mol Cell Proteomics, 2014, 13(10): 2705-2724.
[28]	Marin-Mogollon C, van de Vegte-Bolmer M, van Gemert GJ, et al. The Plasmodium falciparum male gametocyte protein P230p, a paralog of P230, is vital for ookinete formation and mosquito transmission[J]. Sci Rep, 2018, 8(1): 14902.
[29]	van Dijk MR, Khan SM, et al. Three members of the 6-cys protein family of Plasmodium play a role in gamete fertility[J]. PLoS Pathog, 2010, 6(4): e1000853.
[30]	van Schaijk BC, van Dijk MR, van de Vegte-Bolmer M, et al. Pfs47, paralog of the male fertility factor Pfs48/45, is a female specific surface protein in Plasmodium falciparum[J]. Mol Biochem Parasitol, 2006, 149(2): 216-222.
[31]	Brukman NG, Li X, Podbilewicz B. Fusexins, HAP2/GCS1 and evolution of gamete fusion[J]. Front Cell DevBiol, 2021, 9:824024.
[32]	Tentokam BCN, Amaratunga C, Alani NAH, et al. Naturally acquired antibody response to malaria transmission blocking vaccine candidate Pvs230 domain 1[J]. Front Immunol, 2019, 10: 2295. doi: 10.3389/fimmu.2019.02295 pmid: 31636633
[33]	Moskalyk LA, Oo MM, Jacobs-Lorena M. Peritrophic matrix proteins of Anopheles gambiae and Aedes aegypti[J]. Insect Mol Biol, 1996, 5(4): 261-268. doi: 10.1111/j.1365-2583.1996.tb00100.x pmid: 8933177
[34]	Li FW, Patra KP, Vinetz JM. An anti-chitinase malaria transmission-blocking single-chain antibody as an effector molecule for creating a Plasmodium falciparum-refractory mosquito[J]. J Infect Dis, 2005, 192(5): 878-887.
[35]	Li FW, Patra KP, Yowell CA, et al. Apical surface expression of aspartic protease Plasmepsin 4, a potential transmission-blocking target of the Plasmodium ookinete[J]. J Biol Chem, 2010, 285(11): 8076-8083. doi: 10.1074/jbc.M109.063388 pmid: 20056606
[36]	Wang PP, Jiang XF, Bai J, et al. Characterization of PSOP26 as an ookinete surface antigen with improved transmission-blocking activity when fused with PSOP25[J]. Parasit Vectors, 2022, 15(1): 175.
[37]	Saxena AK, Wu YM, Garboczi DN. Plasmodium p25 and p28 surface proteins: potential transmission-blocking vaccines[J]. Eukaryot Cell, 2007, 6(8): 1260-1265. doi: 10.1128/EC.00060-07 pmid: 17557884
[38]	Tomas AM, Margos G, Dimopoulos G, et al. P25 and P28 proteins of the malaria ookinete surface have multiple and partially redundant functions[J]. EMBO J, 2001, 20(15): 3975-3983. doi: 10.1093/emboj/20.15.3975 pmid: 11483501
[39]	Zheng L, Xu WM, Liu YJ, et al. Transmission-blocking vaccine candidate of Plasmodium vivax Pvs25 is highly conservative among Chinese isolates[J]. Chin J Parasitol Parasit Dis, 2004, 22(1): 16-19. (in Chinese)
	(郑丽, 徐卫民, 刘英杰, 等. 间日疟原虫传播阻断疫苗候选抗原Pvs25中国分离株高度保守[J]. 中国寄生虫学与寄生虫病杂志, 2004, 22(1): 16-19.)
[40]	Zheng WQ, Kou X, Du YT, et al. Identification of three ookinete-specific genes and evaluation of their transmission-blocking potentials in Plasmodium berghei[J]. Vaccine, 2016, 34(23): 2570-2578.
[41]	Ukegbu CV, Giorgalli M, Tapanelli S, et al. PIMMS43 is required for malaria parasite immune evasion and sporogonic development in the mosquito vector[J]. Proc Natl Acad Sci USA, 2020, 117(13): 7363-7373. doi: 10.1073/pnas.1919709117 pmid: 32165544
[42]	Tachibana M, Iriko H, Baba M, et al. PSOP1, putative secreted ookinete protein 1, is localized to the micronemes of Plasmodium yoelii and P. berghei ookinetes[J]. Parasitol Int, 2021, 84: 102407.
[43]	Coutinho-Abreu IV, Ramalho-Ortigao M. Transmission blocking vaccines to control insect-borne diseases: a review[J]. Mem Inst Oswaldo Cruz, 2010, 105(1): 1-12.
[44]	Lavazec C, Boudin C, Lacroix R, et al. Carboxypeptidases B of Anopheles gambiae as targets for a Plasmodium falciparumtransmission-blocking vaccine[J]. Infect Immun, 2007, 75(4): 1635-1642. pmid: 17283100
[45]	Dinglasan RR, Kalume DE, Kanzok SM, et al. Disruption of Plasmodium falciparum development by antibodies against a conserved mosquito midgut antigen[J]. Proc Natl Acad Sci USA, 2007, 104(33): 13461-13466. pmid: 17673553
[46]	Dinglasan RR, Jacobs-Lorena M. Flipping the paradigm on malaria transmission-blocking vaccines[J]. Trends Parasitol, 2008, 24(8): 364-370. doi: 10.1016/j.pt.2008.05.002 pmid: 18599352
[47]	Lecona-Valera AN, Tao DY, Rodríguez MH, et al. An antibody against an Anopheles albimanus midgut myosin reduces Plasmodium berghei oocyst development[J]. Parasit Vectors, 2016, 9(1): 274.
[48]	Mathias DK, Plieskatt JL, Armistead JS, et al. Expression, immunogenicity, histopathology, and potency of a mosquito-based malaria transmission-blocking recombinant vaccine[J]. Infect Immun, 2012, 80(4): 1606-1614. doi: 10.1128/IAI.06212-11 pmid: 22311924
[49]	Armistead JS, Morlais I, Mathias DK, et al. Antibodies to a single, conserved epitope in Anopheles APN1 inhibit universal transmission of Plasmodium falciparum and Plasmodium vivaxmalaria[J]. Infect Immun, 2014, 82(2): 818-829. doi: 10.1128/IAI.01222-13 pmid: 24478095
[50]	Zhang GW, Niu GD, Franca CM, et al. Anopheles midgut FREP1 mediates Plasmodium invasion[J]. J Biol Chem, 2015, 290(27): 16490-16501.
[51]	Dong YM, Simões ML, Marois E, et al. CRISPR/Cas9-mediated gene knockout of Anopheles gambiae FREP1 suppresses malaria parasite infection[J]. PLoS Pathog, 2018, 14(3): e1006898.
[52]	Nourani L, Mehrizi AA, Pirahmadi S, et al. CRISPR/Cas advancements for genome editing, diagnosis, therapeutics, and vaccine development for Plasmodium parasites, and genetic engineering of Anopheles mosquito vector[J]. Infect Genet Evol, 2023, 109:105419.
[53]	Cui YJ, Niu GD, Li VL, et al. Analysis of blood-induced Anopheles gambiae midgut proteins and sexual stage Plasmodium falciparum interaction reveals mosquito genes important for malaria transmission[J]. Sci Rep, 2020, 10(1): 14316.
[54]	Liu F, Li L, Zheng WQ, et al. Characterization of Plasmodium berghei Pbg37 as both a pre- and post-fertilization antigen with transmission-blocking potential[J]. Infect Immun, 2018, 86(8): e00785.
[55]	Yang F, Liu F, Yu XX, et al. Evaluation of two sexual-stage antigens as bivalent transmission-blocking vaccines in rodent malaria[J]. Parasit Vectors, 2021, 14(1): 241.
[56]	Sala KA, Nishiura H, Upton LM, et al. The Plasmodium berghei sexual stage antigen PSOP12 induces anti-malarial transmission blocking immunity both in vivo and in vitro[J]. Vaccine, 2015, 33(3): 437-445. doi: 10.1016/j.vaccine.2014.11.038 pmid: 25454088
[57]	Kou X, Zheng WQ, Du F, et al. Erratum to: characterization of a Plasmodium berghei sexual stage antigen PbPH as a new candidate for malaria transmission-blocking vaccine[J]. Parasit Vectors, 2017, 10(1): 84.
[58]	Carter R. Transmission blocking malaria vaccines[J]. Vaccine, 2001, 19(17/18/19): 2309-2314.
[59]	Mair GR, Lasonder E, Garver LS, et al. Universal features of post-transcriptional gene regulation are critical for Plasmodium zygote development[J]. PLoS Pathog, 2010, 6(2): e1000767.
[60]	Shi YP, Das P, Holloway B, et al. Development, expression, and murine testing of a multistage Plasmodium falciparum malaria vaccine candidate[J]. Vaccine, 2000, 18(25): 2902-2914. pmid: 10812234
[61]	Mizutani M, Iyori M, Blagborough AM, et al. Baculovirus-vectored multistage Plasmodium vivax vaccine induces both protective and transmission-blocking immunities against transgenic rodent malaria parasites[J]. Infect Immun, 2014, 82(10): 4348-4357.
[62]	Zheng L, Pang W, Qi ZM, et al. Effects of transmission-blocking vaccines simultaneously targeting pre- and post-fertilization antigens in the rodent malaria parasite Plasmodium yoelii[J]. Parasit Vectors, 2016, 9(1): 433.
[63]	Singh SK, Plieskatt J, Chourasia BK, et al. A reproducible and scalable process for manufacturing a Pfs48/45 based Plasmodium falciparum transmission-blocking vaccine[J]. Front Immunol, 2020, 11:606266.
[64]	da Veiga GTS, Moriggi MR, Vettorazzi JF, et al. Plasmodium vivax vaccine: what is the best way to go?[J]. Front Immunol, 2022, 13:910236.
[65]	Tachibana M, Sato C, Otsuki H, et al. Plasmodium vivax gametocyte protein Pvs230 is a transmission-blocking vaccine candidate[J]. Vaccine, 2012, 30(10): 1807-1812. doi: 10.1016/j.vaccine.2012.01.003 pmid: 22245309
[66]	Mariano RMDS, Gonçalves AAM, Oliveira DS, et al. A review of major patents on potential malaria vaccine targets[J]. Pathogens, 2023, 12(2): 247.
[67]	Rui E, Fernandez-Becerra C, Takeo S, et al. Plasmodium vivax: comparison of immunogenicity among proteins expressed in the cell-free systems of Escherichia coli and wheat germ by suspension array assays[J]. Malar J, 2011, 10: 192.
[68]	Tachibana M, Miura K, Takashima E, et al. Identification of domains within Pfs230 that elicit transmission blocking antibody responses[J]. Vaccine, 2019, 37(13): 1799-1806. doi: S0264-410X(19)30216-6 pmid: 30824357
[69]	Tachibana M, Suwanabun N, Kaneko O, et al. ,, Plasmodium vivax gametocyte proteins, Pvs48/45 and Pvs47, induce transmission-reducing antibodies by DNA immunization[J]. Vaccine, 2015, 33(16): 1901-1908. doi: 10.1016/j.vaccine.2015.03.008 pmid: 25765968
[70]	Mamedov T, Cicek K, Miura K, et al. A Plant-produced in vivo deglycosylated full-length Pfs48/45 as a transmission-blocking vaccine candidate against malaria[J]. Sci Rep, 2019, 9(1): 9868.
[71]	Asali S, Raz A, Turki H, et al. Restricted genetic heterogeneity of the Plasmodium vivax transmission-blocking vaccine (TBV) candidate Pvs48/45 in a low transmission setting: Implications for the Plasmodium vivax malaria vaccine development[J]. Infect Genet Evol, 2021, 89: 104710.
[72]	McLeod B, Mabrouk MT, Miura K, et al. Vaccination with a structure-based stabilized version of malarial antigen Pfs48/45 elicits ultra-potent transmission-blocking antibody responses[J]. Immunity, 2022, 55(9): 1680-1692.e8. doi: 10.1016/j.immuni.2022.07.015 pmid: 35977542
[73]	Blagborough AM, Musiychuk K, Bi H, et al. Transmission blocking potency and immunogenicity of a plant-produced Pvs25-based subunit vaccine against Plasmodium vivax[J]. Vaccine, 2016, 34(28): 3252-3259. doi: 10.1016/j.vaccine.2016.05.007 pmid: 27177945
[74]	Malkin EM, Durbin AP, Diemert DJ, et al. Phase 1 vaccine trial of Pvs25H: a transmission blocking vaccine for Plasmodium vivax malaria[J]. Vaccine, 2005, 23(24): 3131-3138.
[75]	Sagara I, Healy SA, Assadou MH, et al. Safety and immunogenicity of Pfs25H-EPA/Alhydrogel, a transmission-blocking vaccine against Plasmodium falciparum: a randomised, double-blind, comparator-controlled, dose-escalation study in healthy Malian adults[J]. Lancet Infect Dis, 2018, 18(9): 969-982.
[76]	Chichester JA, Green BJ, Jones RM, et al. Safety and immunogenicity of a plant-produced Pfs25 virus-like particle as a transmission blocking vaccine against malaria: a phase 1 dose-escalation study in healthy adults[J]. Vaccine, 2018, 36(39): 5865-5871. doi: S0264-410X(18)31159-9 pmid: 30126674
[77]	Wu YM, Ellis RD, Shaffer D, et al. Phase 1 trial of malaria transmission blocking vaccine candidates Pfs25 and Pvs25 formulated with montanide ISA 51[J]. PLoS One, 2008, 3(7): e2636.
[78]	Patra KP, Li FW, Carter D, et al. Alga-produced malaria transmission-blocking vaccine candidate Pfs25 formulated with a human use-compatible potent adjuvant induces high-affinity antibodies that block Plasmodium falciparum infection of mosquitoes[J]. Infect Immun, 2015, 83(5): 1799-1808.
[79]	Yu SS, Wang J, Luo X, et al. Transmission-blocking strategies against malaria parasites during their mosquito stages[J]. Front Cell Infect Microbiol, 2022, 12:820650.
[80]	Ayala D, Akone-Ella O, Rahola N, et al. Natural Wolbachia infections are common in the major malaria vectors in Central Africa[J]. Evol Appl, 2019, 12(8): 1583-1594.
[81]	Walker T, Quek S, Jeffries CL, et al. Stable high-density and maternally inherited Wolbachia infections in Anopheles moucheti and Anopheles demeilloni mosquitoes[J]. Curr Biol, 2021, 31(11): 2310-2320.e5.
[82]	Gomes FM, Hixson BL, Tyner MDW, et al. Effect of naturally occurring Wolbachia in Anopheles gambiae s.l. mosquitoes from Mali on Plasmodium falciparum malaria transmission[J]. Proc Natl Acad Sci USA, 2017, 114(47): 12566-12571.
[83]	Gabrieli P, Caccia S, Varotto-Boccazzi I, et al. Mosquito trilogy: microbiota, immunity and pathogens, and their implications for the control of disease transmission[J]. Front Microbiol, 2021, 12: 630438.
[84]	Duffy PE. Transmission-blocking vaccines: harnessing herd immunity for malaria elimination[J]. Expert Rev Vaccines, 2021, 20(2): 185-198. doi: 10.1080/14760584.2021.1878028 pmid: 33478283
[85]	Coelho CH, Rappuoli R, Hotez PJ, et al. Transmission-blocking vaccines for malaria: time to talk about vaccine introduction[J]. Trends Parasitol, 2019, 35(7): 483-486. doi: S1471-4922(19)30084-4 pmid: 31153722