Parasitic diseases continue to impose a significant global health burden, particularly in low- and middle-income countries, underscoring an urgent need for effective vaccines to combat these often fatal infections.
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Introduction to Parasitic Diseases
The World Health Organization (WHO) estimates that nearly 2.5 million people throughout the world die each year due to parasitic diseases, with over two billion people likely infected with at least one tropical parasitic disease. Furthermore, a recent The Lancet Infectious Diseases study reported that parasitic infections contributed to 704 million disability-adjusted life-years (DALYs) in 2019, 309 million of which affected children five years of age and younger, with individuals residing in low- and middle-income countries most frequently affected by these diseases.
Parasites can be transmitted to humans through several sources, including animals, blood, food, insects, and water. Various animals can transmit parasites to humans, including pets like dogs and cats, as well as wild animals like raccoons.
Several parasite diseases are bloodborne, some of which include Chagas disease, leishmaniasis, malaria, toxoplasmosis, African trypanosomiasis, and babesiosis2. Parasites can also be transmitted in foods such as undercooked fish and meat, as well as raw vegetables that have been contaminated by human or animal feces. Some of the most common parasites that are transmitted in foods include helminthic roundworms, tapeworms, and flukes.
To date, only one vaccine has been developed against parasitic diseases in humans, along with five vaccines licensed for veterinary use. Due to the lack of immunizations against these pathogens, parasite control has conventionally been maintained through chemical treatments. However, these methods can induce toxicity in both animals and the environment and contribute to the emergence of resistant parasites3.
Discover more: What are Protozoa?
Challenges in Developing Vaccines for Parasitic Diseases
Parasites are eukaryotic organisms that can only survive by living on or in a host organism. They can be single- or multicellular and can be further classified as protozoa, helminths, ectoparasites, and ticks4.
Parasites have sophisticated ways in which they can evade the host immune system during an infection, many of which are specific to the organism. For example, certain Plasmodium sporozoites, which are typically carried by mosquitos, can overcome the innate defense response of the human skin where the mosquito bite has occurred through various mechanisms, including rapid extracellular gliding motility to enter blood vessels and cell-traversal motility to infect hepatocytes and escape degradation by lysosomes4.
Despite these observations, parasites have complex life cycles and can evade the host immune system through many other mechanisms that remain unclear. The complexity of the parasite life cycle also makes it difficult to determine which targets should be used to develop vaccines against, as different parasitic proteins are expressed at various life stages.
Additional challenges in vaccine development include the lack of in vitro cellular and biochemical assays, which has limited researchers' ability to understand the biological complexity of parasites and host-parasite interactions5. As a result, most vaccine studies must often be conducted in in vivo experiments, which are usually expensive and associated with limitations.
Current Approaches to Vaccine Development
Protein Subunit Vaccines
To date, RTS,S/AS01 is the only antimalarial vaccine that has been approved for human use; however, this vaccine is associated with low efficacy ranging from 26-50%6. RTS,S/AS01 is a recombinant protein vaccine that consists of the Plasmodium falciparum circumsporozoite (CS) protein that targets the pre-erythrocytic parasite stage to prevent initial infection.
Recently, over 20 other malaria vaccines that target both the pre-erythrocytic and blood stages of infection have been evaluated in clinical trials, most of which are pre-erythrocytic stage vaccines. Of these, the chimpanzee adenovirus serotype 63 (ChAd63) and modified Ankara (MVA) vaccine have passed phase I clinical trials. In these clinical trials, ChAd63/MVA, which targets the malaria antigenic sequence ME-TRAP, exhibited high efficacy with no toxicity6.
DNA and mRNA Vaccines
The rapid spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the coronavirus disease 2019 (COVID-19), enlisted scientists throughout the world to come together to rapidly develop an effective vaccine capable of preventing viral transmission and reducing the severity of infection.
The messenger ribonucleic acid (mRNA) platform, which both Pfizer/BioNTech and Moderna utilized, has demonstrated the numerous advantages associated with these vaccines and their potential to be used for combatting other infectious diseases. These include the ability to induce a type-I innate immune response, which leads to a strong cytotoxic T-cell response without the use of any adjuvants.
Although few, many researchers have investigated the potential efficacy of mRNA vaccines for preventing parasitic diseases. In 2017, researchers in China published their findings on a self-amplifying mRNA vaccine candidate against Toxoplasma gondii infection that increased survival rates in mice following subsequent challenges with the parasite while also reducing the prevalence of brain cysts in a chronic mouse model of T. gondii infection7.
Live Attenuated and Inactivated Vaccines
Despite recent advancements that have been made in the development and dissemination of malaria vaccines, these vaccines are associated with limited long-term protection. Additional limitations include targeting a single parasite species and parasitic antigen, which increases the risk of resistant parasites, as well as the lack of vaccines capable of blocking Plasmodium infection and reducing further transmission8.
To overcome these challenges, researchers have investigated the potential of vaccinating individuals and animals with whole Plasmodium sporozoites (WSpz), which would allow for the targeting of a broad range of antigens as compared to conventional subunit vaccines. The Sanaria® PfSPZ Vaccine, which consists of cryopreserved radiation-attenuated Pf sporozoites (RAS), has been shown to protect malaria-naïve individuals from infection in the United States and Europe, as well as malaria-exposed adults in Africa8.
Genetically attenuated parasites (GAPs) have been genetically manipulated to lack one or more genes needed for the parasite to establish symptomatic blood-stage infection. Although the PfSPZ-GA1 did not confer any protection when evaluated in a clinical setting, other Pf GAPs are currently being investigated.
Assessing Emerging Vaccines Using Spectroscopy
Conclusion
In conclusion, the fight against parasitic diseases remains a pressing global health priority, particularly in regions with limited access to healthcare resources. Despite numerous challenges, including the complex life cycles of parasites and their ability to evade immune responses, innovative approaches in vaccine development offer hope.
Advances in protein subunit, DNA, mRNA, and live-attenuated vaccines are paving the way for new preventive strategies. While only a few vaccines are currently available, ongoing research into multi-target, highly effective vaccines promises to reduce the global burden of parasitic diseases, offering the potential to protect millions of lives worldwide.
References
- IHME Pathogen Core Group (2024). Global Burden associated with 85 pathogens in 2019: a systemic analysis for the Global Burden of Disease Study 2019. The Lancet Infectious Disease 24(8); P868-895. doi:10.1016/S1473-3099(24)00158-0.
- “What Causes Parasitic Diseases” [Online]. Available from: https://www.cdc.gov/parasites/causes/index.html.
- Daniel de Barros, L., & Cerqueira-Cezar, C. K. (2023). Editorial: Vaccines against parasitic infections in domestic animals. Frontiers in Parasitology 10. doi:10.3389/fvets.2023.1144700.
- Chulanetra, M., & Chaicumpa, W. (2021). Revisiting the Mechanisms of Immune Evasion Employed by Huma Parasites. Frontiers in Cell and Infection Microbiology. doi:10.3389/fcimb.2021.702125.
- Morrison, W. & Tomley, F. (2016). Development of vaccines for parasitic diseases of animals: Challenges and opportunities. Parasite Immunology 38(12); 707-708. doi:10.1111/pim.12398
- Skwarczynski, M., Chanbdrudu, S., Rigau-Planella, B., et al. (2020). Progress in the Development of Subunit Vaccines against Malaria. Vaccines 8(3); 373. doi:3390/vaccines8030373.
- Versteeg, L., Almutairi, M. M., Hotez, P. J., & Pollet, J. (2019). Enlisting the mRNA Vaccine Platform to Combat Parasitic Infections. Vaccines 7(4); 122. doi:10.3390/vaccines7040122.
- Moita, D., & Prudencio, M. (2024). A new malaria vaccination tool based on replication-competent Plasmodium falciparum parasites. EMBO Molecular Medicine 16(4); 667-669. doi:10.1038/s44321-024-00056-8.
Further Reading
Effective Plasmid DNA Delivery Achieved with Zwitterionic Polymer Complex