DOI QR코드

DOI QR Code

Virus-like particles expressing microneme-associated antigen of Plasmodium berghei confer better protection than those expressing apical membrane antigen 1

  • Min-Ju Kim (Department of Biomedical Science, Graduate School, Kyung Hee University) ;
  • Ki Back Chu (Department of Parasitology, Inje University College of Medicine) ;
  • Keon-Woong Yoon (Department of Biomedical Science, Graduate School, Kyung Hee University) ;
  • Hae-Ji Kang (Department of Microbiology, Dongguk University College of Medicine) ;
  • Dong-Hun Lee (Department of Biomedical Science, Graduate School, Kyung Hee University) ;
  • Eun-Kyung Moon (Department of Medical Zoology, Kyung Hee University School of Medicine) ;
  • Fu-Shi Quan (Department of Medical Zoology, Kyung Hee University School of Medicine)
  • Received : 2024.03.07
  • Accepted : 2024.04.18
  • Published : 2024.05.31

Abstract

Malaria is a global disease affecting a large portion of the world's population. Although vaccines have recently become available, their efficacies are suboptimal. We generated virus-like particles (VLPs) that expressed either apical membrane antigen 1 (AMA1) or microneme-associated antigen (MIC) of Plasmodium berghei and compared their efficacy in BALB/c mice. We found that immune sera acquired from AMA1 VLP- or MIC VLP-immunized mice specifically interacted with the antigen of choice and the whole P. berghei lysate antigen, indicating that the antibodies were highly parasite-specific. Both VLP vaccines significantly enhanced germinal center B cell frequencies in the inguinal lymph nodes of mice compared with the control, but only the mice that received MIC VLPs showed significantly enhanced CD4+ T cell responses in the blood following P. berghei challenge infection. AMA1 and MIC VLPs significantly suppressed TNF-α and interleukin-10 production but had a negligible effect on interferon-γ. Both VLPs prevented excessive parasitemia buildup in immunized mice, although parasite burden reduction induced by MIC VLPs was slightly more effective than that induced by AMA1. Both VLPs were equally effective at preventing body weight loss. Our findings demonstrated that the MIC VLP was an effective inducer of protection against murine experimental malaria and should be the focus of further development.

Keywords

Acknowledgement

This study was financially supported by the Core Research Institute (CRI) Program, the Basic Science Research Program through the National Research Foundation of Korea (NRF), Ministry of Education (NRF2018R1A6A1A03025124).

References

  1. Aderinto N, Olatunji G, Kokori E, Sikirullahi S, Aboje JE, et al. A perspective on Oxford's R21/Matrix-MTM malaria vaccine and the future of global eradication efforts. Malar J 2024;23(1):16. https://doi.org/10.1186/s12936-024-04846-w
  2. World Health Organization: World Malaria Report 2021. Geneva, Switzerland. World Health Organization. Geneva, Switzerland. 2021.
  3. Marwa K, Kapesa A, Baraka V, Konje E, Kidenya B, et al. Therapeutic efficacy of artemether-lumefantrine, artesunate-amodiaquine and dihydroartemisinin-piperaquine in the treatment of uncomplicated Plasmodium falciparum malaria in Sub-Saharan Africa: a systematic review and meta-analysis. PLoS One 2022;17(3):e0264339. https://doi.org/10.1371/journal.pone.0264339
  4. Panda S, Swaminathan S, Hyder KA, Christophel EM, Pendse RN, et al. Drug resistance in malaria, tuberculosis, and HIV in South East Asia: biology, programme, and policy considerations. BMJ 2017;358:j3545. https://doi.org/10.1136/bmj.j3545
  5. Balikagala B, Fukuda N, Ikeda M, Katuro OT, Tachibana SI, et al. Evidence of artemisinin-resistant malaria in Africa. N Engl J Med 2021;385:1163-1171. https://doi.org/10.1056/NEJMoa2101746
  6. Chenet SM, Akinyi Okoth S, Huber CS, Chandrabose J, Lucchi NW, et al. Independent emergence of the Plasmodium falciparum Kelch propeller domain mutant allele C580Y in Guyana. J Infect Dis 2016;213(9):1472-1475. https://doi.org/10.1093/infdis/jiv752
  7. Kennedy DA, Read AF. Why the evolution of vaccine resistance is less of a concern than the evolution of drug resistance. Proc Natl Acad Sci USA 2018;115(51):12878-12886. https://doi.org/10.1073/pnas.1717159115
  8. Micoli F, Bagnoli F, Rappuoli R, Serruto D. The role of vaccines in combatting antimicrobial resistance. Nat Rev Microbiol 2021;19(5):287-302. https://doi.org/10.1038/s41579-020-00506-3
  9. Schmit N, Topazian HM, Natama HM, Bellamy D, Traore O, et al. The public health impact and cost-effectiveness of the R21/Matrix-M malaria vaccine: a mathematical modelling study. Lancet Infect Dis 2024;24(5):465-475. https://doi.org/10.1016/s1473-3099(23)00816-2
  10. Hammershaimb EA, Berry AA. Pre-erythrocytic malaria vaccines: RTS,S, R21, and beyond. Expert Rev Vaccines 2024;23:49-52. https://doi.org/10.1080/14760584.2023.2292204
  11. Laurens MB. RTS,S/AS01 vaccine (MosquirixTM): an overview. Hum Vaccin Immunother 2020;16:480-489. https://doi.org/10.1080/21645515.2019.1669415
  12. Datoo MS, Dicko A, Tinto H, Ouedraogo JB, Hamaluba M, et al. Safety and efficacy of malaria vaccine candidate R21/Matrix-M in African children: a multicentre, double-blind, randomised, phase 3 trial. Lancet 2024;403:533-544. https://doi.org/10.1016/s0140-6736(23)02511-4
  13. Schneider CG, Fey J, Zou X, Gerbasi V, Savransky T, et al. Norovirus-VLPs expressing pre-erythrocytic malaria antigens induce functional immunity against sporozoite infection. Vaccine 2022;40(31):4270-4280. https://doi.org/10.1016/j.vaccine.2022.05.076
  14. Yao G, Min H, Yu X, Liu F, Cui L, et al. A nanoparticle vaccine displaying the ookinete PSOP25 antigen elicits transmission-blocking antibody response against Plasmodium berghei. Parasit Vectors 2023;16(1):403. https://doi.org/10.1186/s13071-023-06020-8
  15. Tottey S, Shoji Y, Mark Jones R, Musiychuk K, Chichester JA, et al. Engineering of a plant-produced virus-like particle to improve the display of the Plasmodium falciparum Pfs25 antigen and transmission-blocking activity of the vaccine candidate. Vaccine 2023;41(4):938-944. https://doi.org/10.1016/j.vaccine.2022.12.048
  16. Saveria T, Parthiban C, Seilie AM, Brady C, Martinez A, et al. Needle-free, spirulina-produced Plasmodium falciparum circumsporozoite vaccination provides sterile protection against pre-erythrocytic malaria in mice. NPJ Vaccines 2022;7(1):113. https://doi.org/10.1038/s41541-022-00534-5
  17. Lee SH, Chu KB, Kang HJ, Basak S, Kim MJ, et al. Virus-like particles expressing Plasmodium berghei MSP-8 induce protection against P. berghei infection. Parasite Immunol 2020;42(11):e12781. https://doi.org/10.1111/pim.12781
  18. Harmsen C, Turner L, Thrane S, Sander AF, Theander TG, et al. Immunization with virus-like particles conjugated to CIDRα1 domain of Plasmodium falciparum erythrocyte membrane protein 1 induces inhibitory antibodies. Malar J 2020;19(1):132. https://doi.org/10.1186/s12936-020-03201-z
  19. Kim MJ, Chu KB, Kang HJ, Yoon KW, Lee DH, et al. Influenza virus-like particle vaccine containing both apical membrane antigen 1 and microneme-associated antigen proteins of Plasmodium berghei confers protection in mice. BMC Immunol 2022;23(1):21. https://doi.org/10.1186/s12865-022-00494-4
  20. Lee DH, Chu KB, Kang HJ, Lee SH, Chopra M, et al. Protection induced by malaria virus-like particles containing codon-optimized AMA-1 of Plasmodium berghei. Malar J 2019;18(1):394. https://doi.org/10.1186/s12936-019-3017-2
  21. Chu KB, Kim SS, Lee SH, Lee DH, Kim AR, et al. Immune correlates of resistance to Trichinella spiralis reinfection in mice. Parasites Hosts Dis 2016;54(5):637-643. https://doi.org/10.3347/kjp.2016.54.5.637
  22. Lee SH, Kang HJ, Chu KB, Basak S, Lee DH, et al. Protective immunity induced by virus-like particle containing merozoite surface protein 9 of Plasmodium berghei. Vaccines (Basel) 2020; 8(3):428. https://doi.org/10.3390/vaccines8030428
  23. Treeck M, Zacherl S, Herrmann S, Cabrera A, Kono M, et al. Functional analysis of the leading malaria vaccine candidate AMA-1 reveals an essential role for the cytoplasmic domain in the invasion process. PLoS Pathog 2009;5(3):e1000322. https://doi.org/10.1371/journal.ppat.1000322
  24. Lal K, Prieto JH, Bromley E, Sanderson SJ, Yates JR 3rd, et al. Characterisation of Plasmodium invasive organelles; an ookinete microneme proteome. Proteomics 2009;9(5):1142-1151. https://doi.org/10.1002/pmic.200800404
  25. Dutta S, Haynes JD, Barbosa A, Ware LA, Snavely JD, et al. Mode of action of invasion-inhibitory antibodies directed against apical membrane antigen 1 of Plasmodium falciparum. Infect Immun 2005;73(4):2116-2122. https://doi.org/10.1128/iai.73.4.2116-2122.2005
  26. Yoshida S, Nagumo H, Yokomine T, Araki H, Suzuki A, et al. Plasmodium berghei circumvents immune responses induced by merozoite surface protein 1- and apical membrane antigen 1-based vaccines. PLoS One 2010;5(10):e13727. https://doi.org/10.1371/journal.pone.001372
  27. Kim MJ, Chu KB, Lee SH, Kang HJ, Yoon KW, et al. Recombinant vaccinia virus expressing Plasmodium berghei apical membrane antigen 1 or microneme protein enhances protection against P. berghei infection in mice. Trop Med Infect Dis 2022;7(11):350. https://doi.org/10.3390/tropicalmed7110350
  28. Freitas do Rosario AP, Muxel SM, Rodriguez-Malaga SM, Sardinha LR, Zago CA, et al. Gradual decline in malaria-specific memory T cell responses leads to failure to maintain long-term protective immunity to Plasmodium chabaudi AS despite persistence of B cell memory and circulating antibody. J Immunol 2008;181(12):8344-8355. https://doi.org/10.4049/jimmunol.181.12.8344
  29. da Silva HB, de Salles EM, Panatieri RH, Boscardin SB, Rodriguez-Malaga SM, et al. IFN-γ-induced priming maintains long-term strain-transcending immunity against blood-stage Plasmodium chabaudi malaria. J Immunol 2013;191(10):5160-5169. https://doi.org/10.4049/jimmunol.1300462
  30. Prakash D, Fesel C, Jain R, Cazenave PA, Mishra GC, et al. Clusters of cytokines determine malaria severity in Plasmodium falciparum-infected patients from endemic areas of Central India. J Infect Dis 2006;194(2):198-207. https://doi.org/10.1086/504720
  31. Niikura M, Kamiya S, Nakane A, Kita K, Kobayashi F. IL-10 plays a crucial role for the protection of experimental cerebral malaria by co-infection with non-lethal malaria parasites. Int J Parasitol 2010;40(1):101-108. https://doi.org/10.1016/j.ijpara.2009.08.009
  32. Kossodo S, Monso C, Juillard P, Velu T, Goldman M, et al. Interleukin-10 modulates susceptibility in experimental cerebral malaria. Immunology 1997;91(4):536-540. https://doi.org/10.1046/j.1365-2567.1997.00290.x
  33. Lyke KE, Burges R, Cissoko Y, Sangare L, Dao M, et al. Serum levels of the proinflammatory cytokines interleukin-1 beta (IL-1beta), IL-6, IL-8, IL-10, tumor necrosis factor alpha, and IL-12(p70) in Malian children with severe Plasmodium falciparum malaria and matched uncomplicated malaria or healthy controls. Infect Immun 2004;72(10):5630-5637. https://doi.org/10.1128/iai.72.10.5630-5637.2004
  34. Sobota RS, Goron AR, Berry AA, Bailey JA, Coulibaly D, et al. Serologic and cytokine profiles of children with concurrent cerebral malaria and severe malarial anemia are distinct from other subtypes of severe malaria. Am J Trop Med Hyg 2022;107(2):315-319. https://doi.org/10.4269/ajtmh.22-0135
  35. Weidanz WP, Batchelder JM, Flaherty P, LaFleur G, Wong C, et al. Plasmodium chabaudi adami: use of the B-cell-deficient mouse to define possible mechanisms modulating parasitemia of chronic malaria. Exp Parasitol 2005;111(2):97-104. https://doi.org/10.1016/j.exppara.2005.06.006
  36. de Roquetaillade C, Laouenan C, Mira JP, Roy C, Thuong M, et al. Cytokine profiles in adults with imported malaria. Sci Rep 2023;13(1):10347. https://doi.org/10.1038/s41598-023-36212-2
  37. Ding Y, Xu W, Zhou T, Liu T, Zheng H, et al. Establishment of a murine model of cerebral malaria in KunMing mice infected with Plasmodium berghei ANKA. Parasitology 2016;143(12):1672-1680. https://doi.org/10.1017/s0031182016001475
  38. Zafar I, Taniguchi T, Baghdadi HB, Kondoh D, Rizk MA, et al. Babesia microti alleviates disease manifestations caused by Plasmodium berghei ANKA in murine co-infection model of complicated malaria. Front Cell Infect Microbiol 2023;13:1226088. https://doi.org/10.3389/fcimb.2023.1226088
  39. Fitri LE, Sardjono TW, Winaris N, Pawestri AR, Endharti AT, et al. Bifidobacterium longum administration diminishes parasitemia and inflammation during Plasmodium berghei infection in mice. J Inflamm Res 2023;16:1393-1404. https://doi.org/10.2147/jir.S400782