IJRSI Logo

Plasmodium vivax Vaccine Candidates: Molecular Targets and Challenges in Vaccine Development

Authors

Nisha Siwal

Assistant Professor, Department of Zoology, ANDNNM Mahavidyalaya, Harsh Nagar, Kanpur (Uttar Pradesh) – 208012 (India) (India)

Seema Pandey

Assistant Professor, Department of Zoology, ANDNNM Mahavidyalaya, Harsh Nagar, Kanpur (Uttar Pradesh) – 208012 (India) (India)

Rachana Singh

Assistant professor Dept. of Zoology, DG PG college, Civil lines Kanpur (Uttar Pradesh) India (India)

Article Information

DOI: 10.51244/IJRSI.2026.1306000092

Subject Category: Microbiology

Volume/Issue: 13/6 | Page No: 1307-1315

Publication Timeline

Submitted: 2026-05-20

Accepted: 2026-05-25

Published: 2026-06-24

Abstract

Plasmodium vivax is a major source of malaria morbidity outside of Africa, posing unique problems for vaccine development due to its complex biology, which includes latent liver-stage hypnozoites that promote recurrent infections. P. vivax, on the other hand, has many distinct antigens, spreads fast, and cannot be grown in vitro, making vaccine development problematic. This analysis provides a comprehensive overview of the top P. vivax vaccine candidates at all phases, including pre-erythrocytic, erythrocytic, and transmission-blocking. It includes important antigens like circumsporozoite protein (CSP), thrombospondin-related adhesive protein (TRAP), Duffy binding protein (DBP), merozoite surface protein-1 (MSP-1), and transmission-blocking targets like Pvs25, Pvs28, Pvs230, and Pvs47. We discuss important issues such as antigenic polymorphism, the lack of correlates of protection, and the difficulty of targeting hypnozoites. Recent advances in vaccination stages, such as mRNA-based technologies, viral vectors, and multi-stage immunization techniques, hold promise for overcoming these challenges. To generate an effective P. vivax vaccine, we must understand more about parasites, develop innovative vaccine designs, and collaborate on a global scale.

Keywords

P. vivax, malaria vaccine, transmission-blocking vaccine, Duffy binding protein, antigenic diversity, hypnozoite etc.

Downloads

PDF JATS XML

References

1. Arévalo-Herrera, M., Chitnis, C., Herrera, S. (2010). Current status of Plasmodium vivax vaccine. Human Vaccines, 6(1), 124–132. https://doi.org/10.4161/hv.6.1.10370 [Google Scholar] [Crossref]

2. Arevalo-Herrera, M., Chitnis, C., Herrera, S., & others. (2011). Current status of Plasmodium vivax vaccine. Human Vaccines, 6(1), 124–132. [Google Scholar] [Crossref]

3. Baird, J. K. (2013). Evidence and implications of mortality associated with acute Plasmodium vivax malaria. Clinical Microbiology Reviews, 26(1), 36-57. https://doi.org/10.1128/CMR.00074-12 [Google Scholar] [Crossref]

4. Bergmann-Leitner, E. S., & others. (2010). Immunogenicity and efficacy of novel Plasmodium vivax vaccine candidate antigens. Vaccine, 28(33), 5399–5408. [Google Scholar] [Crossref]

5. Bermúdez, M., Moreno-Pérez, D. A., Arevalo-Herrera, M., Herrera, S., & Patarroyo, M. A. (2018). Plasmodium vivax in vitro continuous culture: The spoke in the wheel. Malaria Journal, 17, 301. https://doi.org/10.1186/s12936-018-2446-1 [Google Scholar] [Crossref]

6. Bernabeu, M., López, F. J., Ferrer, M., & del Portillo, H. A. (2022). Plasmodium vivax VIR proteins: From genomic expansion to functional diversification. Cellular Microbiology, *24*(3), e13788. https://doi.org/10.1111/cmi.13788 [Google Scholar] [Crossref]

7. Canepa, G. E., Molina-Cruz, A., Yenkoidiok-Douti, L., & Barillas-Mury, C. (2018). Plasmodium vivax Pvs47 polymorphism is linked to parasite adaptation to distinct mosquito species. PLoS Neglected Tropical Diseases, 12(7), e0006596. https://doi.org/10.1371/journal.pntd.0006596 [Google Scholar] [Crossref]

8. Carlton, J. M., Adams, J. H., Silva, J. C., Bidwell, S. L., Lorenzi, H., Caler, E., ... & Fraser, C. M. (2008). Comparative genomics of the neglected human malaria parasite Plasmodium vivax. Nature, 455(7214), 757-763. https://doi.org/10.1038/nature07327 [Google Scholar] [Crossref]

9. Chen, E., Salinas, N. D., Huang, Y., Ntumngia, F., Plasencia, M. D., Gross, M. L., Adams, J. H., & Tolia, N. H. (2020). Structural basis for inhibition of Plasmodium vivax invasion by a broadly neutralizing vaccine-induced human antibody. Nature Microbiology, *5*(9), 1107–1117. https://doi.org/10.1038/s41564-020-0740-y [Google Scholar] [Crossref]

10. Chenet, S. M., Tapia, L. L., Escalante, A. A., Durand, S., Lucas, C., Bacon, D. J., & Udhayakumar, V. (2012). Genetic diversity and population structure of genes encoding vaccine candidate antigens of Plasmodium vivax. Malaria Journal, *11*(1), 68. https://doi.org/10.1186/1475-2875-11-68 [Google Scholar] [Crossref]

11. Cole, S., Sheehy, S. H., Drakely, C. J., & Draper, S. J. (2022). Recent advances in the design and delivery of malaria vaccines. Current Opinion in Immunology, *77*, 102208. https://doi.org/10.1016/j.coi.2022.102208 [Google Scholar] [Crossref]

12. Cowman, A. F., Healer, J., Marapana, D., & Marsh, K. (2016). Malaria: Biology and disease. Cell, 167(3), 610–624. https://doi.org/10.1016/j.cell.2016.07.055 [Google Scholar] [Crossref]

13. Das, S., Hertsch, R. A., Llinás, M., & Singh, S. (2009). Comparative genomics of the malaria parasites Plasmodium falciparum and Plasmodium vivax. Current Opinion in Microbiology, 12(4), 415-421. https://doi.org/10.1016/j.mib.2009.06.008 [Google Scholar] [Crossref]

14. Draper, S. J., Sack, B. K., King, C. R., Nielsen, C. M., Rayner, J. C., Higgins, M. K., Long, C. A., & Seder, R. A. (2018). Malaria vaccines: Recent advances and new horizons. Cell Host & Microbe, 24(1), 43–56. https://doi.org/10.1016/j.chom.2018.06.008 [Google Scholar] [Crossref]

15. Gruszczyk, J., Kanjee, U., Chan, L. J., Menant, S., Malleret, B., Lim, N. T. Y., ... & Tham, W. H. (2018). Transferrin receptor 1 is a reticulocyte-specific receptor for Plasmodium vivax. Nature, 559(7715), 585-589. https://doi.org/10.1038/s41467-018-05772-7 [Google Scholar] [Crossref]

16. Gunalan, K., Gao, X., Liew, K. J., Preiser, P. R., & Bozdech, Z. (2016). Role of Plasmodium vivax Duffy-binding protein in erythrocyte invasion and implications for vaccine development. Trends in Parasitology, 32(5), 364–373. https://doi.org/10.1016/j.pt.2016.01.006 [Google Scholar] [Crossref]

17. Gupta, S., Alam, M. T., Bhatnagar, R. K., & Kaur, S. (2014). The Plasmodium vivax virulence genes and their genetic diversity in Indian isolates. PLoS ONE, 9(2), e89653. https://doi.org/10.1371/journal.pone.0089653 [Google Scholar] [Crossref]

18. Herrera, S., Ochoa-Orozco, S. A., & González, I. J. (2020). Prospects for Plasmodium vivax malaria vaccines. Frontiers in Cellular and Infection Microbiology, 10, 614611. https://doi.org/10.3389/fcimb.2020.614611 [Google Scholar] [Crossref]

19. Hoffman, S. L., Vekemans, J., Richie, T. L., & Duffy, P. E. (2015). The march toward malaria vaccines. American Journal of Tropical Medicine and Hygiene, 93(3 Suppl), 1-5. https://doi.org/10.4269/ajtmh.14-0660 [Google Scholar] [Crossref]

20. Howes, R. E., Battle, K. E., Mendis, K. N., Smith, D. L., Cibulskis, R. E., Baird, J. K., & Hay, S. I. (2015). Global epidemiology of Plasmodium vivax. The American Journal of Tropical Medicine and Hygiene, *95*(6 Suppl), 15–34. https://doi.org/10.4269/ajtmh.15-0140 [Google Scholar] [Crossref]

21. King, C. L., Adams, J. H., Xainli, J., & King, C. L. (2018). Strategies for designing and monitoring malaria vaccines targeting diverse antigens. Frontiers in Immunology, *9*, Article 221. https://doi.org/10.3389/fimmu.2018.00221 [Google Scholar] [Crossref]

22. King, C. L., Michon, P., Shakri, A. R., Marcotty, A., Stanisic, D., Zimmerman, P. A., Cole-Tobian, J. L., Mueller, I., Chitnis, C. E., & Cowman, A. F. (2008). Naturally acquired Duffy-binding protein-specific binding inhibitory antibodies confer protection from blood-stage Plasmodium vivax infection. Proceedings of the National Academy of Sciences, 105(24), 8363–8368. https://doi.org/10.1073/pnas.0800377105 [Google Scholar] [Crossref]

23. Liang, H., Narum, D. L., Fuhrmann, S. R., Luu, T., & Sim, B. K. (2020). A recombinant Plasmodium vivax merozoite surface protein 1 (PvMSP1) induces antibody responses to the non-synonymous and allelic variant epitopes. Vaccine, *38*(29), 4540–4549. https://doi.org/10.1016/j.vaccine.2020.04.079 [Google Scholar] [Crossref]

24. Longley, R. J., Salman, A. M., Cottingham, M. G., Ewer, K., Janse, C. J., Khan, S. M., Spencer, A. J., & Hill, A. V. S. (2022). Comparative assessment of vaccine platforms for Plasmodium vivax malaria. npj Vaccines, 7(1), 1–12. https://doi.org/10.1038/s41541-022-00475-0 [Google Scholar] [Crossref]

25. Malkin, E. M., Durbin, A. P., Diemert, D. J., Sattabongkot, J., Wu, Y., Miura, K., Long, C. A., Lambert, L., Miles, A. P., Wang, J., Stowers, A., Miller, L. H., & Saul, A. (2005). Phase 1 vaccine trial of Pvs25H: A transmission-blocking vaccine for Plasmodium vivax malaria. Vaccine, 23(24), 3131–3138.https://doi.org/10.1016/j.vaccine.2004.12.019 [Google Scholar] [Crossref]

26. Maruggi, G., Ulmer, J. B., Rappuoli, R., & Yu, D. (2023). Self-amplifying mRNA-based vaccine technology and its mode of action. Nature Reviews Immunology, *23*(3), 135–155. https://doi.org/10.1038/s41577-022-00774-5 [Google Scholar] [Crossref]

27. Molina-Cruz, A., Barillas-Mury, C., & James, A. A. (2015). Plasmodium vivax immune evasion. PLoS Pathogens, *11*(12), e1005258. https://doi.org/10.1371/journal.ppat.1005258 [Google Scholar] [Crossref]

28. Moreno-Pérez, D. A., Areiza-Rojas, R., Flórez-Buitrago, X., Silva, Y., Patarroyo, M. A. (2017). The Plasmodium vivax thrombospondin-related adhesive protein (PvTRAP): genetic diversity and functional domains. Infection, Genetics and Evolution, 50, 43–52. https://doi.org/10.1016/j.meegid.2017.02.007 [Google Scholar] [Crossref]

29. Mueller, I., Galinski, M. R., Tsuboi, T., & Arevalo-Herrera, M. (2009). Natural acquisition of immunity to Plasmodium vivax: Epidemiological observations and potential targets. Parasitology International, 58(3), 215–223. [Google Scholar] [Crossref]

30. Payne, R. O., Silk, S. E., Elias, S. C., Milne, K. H., Rawlinson, T. A., Llewellyn, D., ... & Draper, S. J. (2017). Human vaccination against Plasmodium vivax Duffy-binding protein induces strain-transcending antibodies. JCI Insight, *2*(12), e93683. https://doi.org/10.1172/jci.insight.93683 [Google Scholar] [Crossref]

31. Perera, K. L., Handunnetti, S. M., Holm, I., Longacre, S., & Mendis, K. (1998). Immunogenicity of Plasmodium vivax Duffy binding protein in humans. The American Journal of Tropical Medicine and Hygiene, 59(4), 597–599. https://doi.org/10.4269/ajtmh.1998.59.597 [Google Scholar] [Crossref]

32. Popovici, J., & Ménard, D. (2015). Challenges in antimalarial drug treatment for vivax malaria control. Trends in Molecular Medicine, *21*(12), 776–788. https://doi.org/10.1016/j.molmed.2015.10.004 [Google Scholar] [Crossref]

33. Price, R. N., Tjitra, E., Guerra, C. A., Yeung, S., White, N. J., & Anstey, N. M. (2007). Vivax malaria: Neglected and not benign. The American Journal of Tropical Medicine and Hygiene, 77(6 Suppl.), 79–87. [Google Scholar] [Crossref]

34. Rahimi, B. A., Thakkinstian, A., White, N. J., Sirivichayakul, C., & Dondorp, A. M. (2014). Severe vivax malaria: A systematic review and meta-analysis of clinical studies. PLoS Neglected Tropical Diseases, 8(2), Article e3077. https://doi.org/10.1371/journal.pntd.0003077 [Google Scholar] [Crossref]

35. Reyes-Sandoval, A., Bachmann, M. F., & Acosta, A. (2021). Plasmodium vivax vaccines: Why are we where we are? Molecular Aspects of Medicine, 80, 100962. https://doi.org/10.1016/j.mam.2021.100962 [Google Scholar] [Crossref]

36. Roobsoong, W., Tharinjaroen, C. S., Sattabongkot, J., & Cui, L. (2023). Advances and challenges in Plasmodium vivax culture systems for vaccine and drug development. Frontiers in Cellular and Infection Microbiology, 13, Article 1182456. https://doi.org/10.3389/fcimb.2023.1182456 [Google Scholar] [Crossref]

37. Scaria, P. V., Rowe, C. G., Chen, L., McLeod, B., Nguyen, T., & Locke, E. (2022). mRNA vaccines against malaria. Tropical Medicine and Infectious Disease, *7**(10), 305. https://doi.org/10.3390/tropicalmed7100305 [Google Scholar] [Crossref]

38. Singh, K., Mukherjee, P., Shakri, A. R., Singh, A., Pandey, G., Bakshi, M., ... & Chitnis, C. E. (2020). Malaria vaccine candidate based on Duffy-binding protein elicits strain-transcending functional antibodies in a Phase I trial. Vaccine, 38(29), 4540–4549. https://doi.org/10.1016/j.vaccine.2020.02.056 [Google Scholar] [Crossref]

39. Stanisic, D. I., McCarthy, J. S., & Good, M. F. (2018). Controlled human malaria infection: Applications, advances, and challenges. Infection and Immunity, 86(1), e00479-17. https://doi.org/10.3389/fimmu.2018.02218 [Google Scholar] [Crossref]

40. Tsuboi, T., Kaslow, D. C., Gozar, M. M., Tachibana, M., Cao, Y. M., & Torii, M. (1998). Sequence polymorphism in two novel Plasmodium vivax ookinete surface proteins, Pvs25 and Pvs28, that are malaria transmission-blocking vaccine candidates. Molecular Medicine, *4*(12), 772–782. https://doi.org/10.1007/s11904-998-0001-1 [Google Scholar] [Crossref]

41. Veiga, M. I., Ferreira, P. E., & Mueller, I. (2023). Genetic diversity and vaccine challenges in Plasmodium vivax. Frontiers in Immunology, 13, 910236. https://doi.org/10.3389/fimmu.2022.910236 [Google Scholar] [Crossref]

42. Wells, T. N. C., Burrows, J. N., & Baird, J. K. (2010). Targeting the hypnozoite reservoir of Plasmodium vivax: The hidden obstacle to malaria elimination. Trends in Parasitology, *26*(3), 145–152. https://doi.org/10.1016/j.pt.2009.12.002 [Google Scholar] [Crossref]

43. World Health Organization. (2024). World malaria report 2024. World Health Organization. [Google Scholar] [Crossref]

44. World Health Organization. (2025). World malaria report 2025. https://www.who.int/publications/i/item/9789240086173 [Google Scholar] [Crossref]

45. Wu, Y., Ellis, R. D., Shaffer, D., Fontes, E., Malkin, E. M., Mahanty, S., ... & Miller, L. H. (2008). Phase 1 trial of malaria transmission blocking vaccine candidates Pfs25 and Pvs25 formulated with montanide ISA 51. PLOS ONE, 3(7), e2636. https://doi.org/10.1371/journal.pone.0002636 [Google Scholar] [Crossref]

Metrics

Views & Downloads

Similar Articles