Introduction

Parasitic diseases are among the most varied and numerous diseases, with a large proportion of the global population infected with parasites. Parasites are capable of causing great pain and even death unless suitable treatment is implemented. 

However, parasites are highly complex organisms that often escape treatment. Vaccines are one of the treatments used to combat parasitic diseases, and through extensive research into parasite behaviour, a range of vaccine designs have shown promise to treat a wide variety of parasitic diseases. 

What are parasites?

Parasites are organisms that live in or on a host organism and feed on the host. There are 3 classes of parasites that are capable of causing disease in humans, which can be named pathogenic parasites:

• Protozoa – These types of parasites are small, microscopic organisms. A  well-known pathogenic protozoan is responsible for causing malaria in humans
• Ectoparasites – these types of parasites are bigger organisms. Examples of ectoparasites include mites, ticks and fleas. Pathogenic ectoparasites mainly transmit diseases rather than cause them. For example, in Lyme disease, ticks carry a bacterial infection which is spread to humans when the ticks feed on their blood
• Helminths – these parasites are much larger organisms that live and feed on hosts but cannot reproduce in the host. Instead, many helminths often produce eggs that are released and spread in the environment, either in soil or water. These eggs hatch under warm, moist, shaded soil. Examples of pathogenic helminths include tapeworms, which live inside the host’s intestine and cause damage to the digestive system

How common are parasitic diseases?

Helminths account for the majority of global parasitic diseases. Almost a quarter of the world's population is infected with soil helminths. These parasites spread through contaminated soil and are known as soil-transmitted helminths. As the eggs of these helminths thrive in warm, shaded soil, the disease is distributed in tropical areas and often in lower-income countries that lack access to clean water. 

Helminth infections can cause great suffering to those infected. Schistosomiasis is among the most dangerous parasitic diseases, capable of causing significant damage to the body. These parasites use freshwater snails as hosts to mature before being able to infect humans, where they lay their eggs in large blood vessels found in the liver and kidneys. Following infection, the movement of eggs can lead to inflammation of tissues and even organ failure and death. 

Other parasitic diseases, such as filariasis, have a low fatality but can result in swelling and disfigurement of the body due to the migration of parasitic eggs around the blood system. This swelling is known as elephantiasis, which can cause severe pain and disability and negatively impact one's quality of life. 

Despite the high prevalence of these parasitic diseases, they have not been eradicated. Parasitic diseases remain absent from the global health agenda and lack funding for studies, so they remain as ‘neglected tropical diseases’. This is largely due to the large geographical and economic barriers faced by low-income countries, which lack the necessary facilities to implement large-scale treatment strategies. In addition, parasites are one of the most complex organisms to study, which makes finding treatments for parasitic diseases all the more difficult. 

What are the challenges in developing vaccines for parasitic diseases? 

How does our immune system work?

The main difficulty of developing a vaccine against parasites is their ability to evade the immune system. Our immune system is highly sensitive to foreign bodies entering our bodies, e.g. bacteria, parasites, and viruses, and we have developed many different ways to protect ourselves from diseases.

These defence mechanisms can range in complexity. Surface-level protectants, such as our nails and skin, act as physical barriers to prevent the entry of different foreign objects. Internally, our nose hairs, stomach acid and lungs can help to forcibly remove pathogens by coughing and sneezing. 

If these pathogens enter our blood system, they can pose a great threat to the body. Luckily, we have many cells specially adapted to sense, recognise and react to these foreign bodies. These cells form part of our immune system, a highly adaptive system able to defend the body from threats. The immune system develops and learns as our body is continuously exposed to the environment, hence it can respond quickly to new threats.

Unfortunately, as our immune system has evolved, so have parasites. They have learnt ways to avoid the immune system and even attempt to gain control over it to avoid being recognised as a threat.

How do parasites avoid our immune system?

• Parasites have many different life stages, which can be hard to isolate and study. The chemicals that our body recognises as foreign also change between their life cycles, making it difficult to create a targeted treatment. In addition, laying eggs makes it difficult to eradicate a parasite, as the eggs can continue to spread in the environment
• Parasites can evade our immune system through a variety of highly specialised mechanisms. The parasite responsible for malaria specifically infects red blood cells by forming a tight rosette shape.⁴ The immune system does not recognise these cells as foreign. Therefore, by hiding in red blood cells, malaria protozoa avoid being recognised and killed by our immune system
• The parasites responsible for the diseases, schistosomiasis and filariasis, can conceal their foreign substances using the host's proteins and chemicals. In this way, they avoid detection by the host’s  immune system¹ 

Existing treatments for parasitic diseases

An anti-malaria vaccine has been in development for many decades. This anti-malaria vaccine was first piloted in 2019 in areas where malaria cases were highly prevalent, and this included countries like Ghana and Kenya. The anti-malaria vaccine has been very successful, reducing both severe hospitalised cases and deaths from malaria by 13%.  Since its introduction, this vaccine has reached over 2 million people and is now part of the standard childhood vaccination programmes, particularly in malaria-prone areas. 

The vaccine is a combination of a protein found on the parasite that causes malaria and a protein found on the hepatitis B virus. When injected into our body, these proteins can activate our immune response to protect against these unknown proteins. If the vaccinated individual were to become infected with the parasite in the future, their body would remember how to protect against the parasite by activating the immune response much more quickly.⁵ 

The components of the vaccine can be mass-produced using a genetically engineered yeast strain to produce these proteins. These types of vaccines are known as recombinant vaccines as they use genetically modified bacteria, viruses or parasites to stimulate an immune response. However, due to difficulties in studying parasites in the laboratory, identifying and purifying the proteins found on parasites is difficult. It may take many more decades to develop vaccines against other parasitic diseases using this method. 

Emerging vaccine designs

A hookworm recombinant vaccine has shown success, with no severe side effects and is moving into phase 2 clinical trials.³ This vaccine targets the blood-feeding stage of adult hookworm parasites and prevents them from breaking down protein in the blood. This would, in theory, starve and kill the adult hookworms. As all adult hookworms need to feed, this vaccine could overcome the challenge of the complex life cycle of parasites. This type of vaccine design could be promising to combat a range of parasitic diseases.⁶

An mRNA-based vaccine against a strain of lethal malaria in mice has shown promise in mouse studies.² This particular strain of malaria produces a chemical, PMIF (Plasmodium macrophage migration inhibitory factor), similar to the host's own chemical MIF (macrophage migration inhibitory factor). These chemicals help to organise the immune system response, however, the parasite can use PMIF and control the immune system to its advantage. The parasite can prevent the proper formation of certain immune cells, responsible for long-term memory and recognition of foreign substances. In this way, the parasite can avoid the immune system's recognition by taking control of it.

This vaccine in this study uses mRNA, which provides a blueprint for our body to create its own PMIF without the parasite present. Once created, our natural immune response against PMIF can be activated. In this study, when the vaccinated mice were introduced to the parasite, they were able to neutralise the PMIF that the parasite had created, reducing the amount by 94%.² 

This study highlighted the potential mRNA vaccines in protecting against malaria. The ideas used here could also be translated to other parasitic diseases and could overcome the challenges associated with immune evasion strategies used by parasites.

Summary

Vaccines have the potential to reduce the global burden of parasitic diseases. Through the use of different biological molecules, including enzymes and mRNA, these vaccine designs have the potential to overcome the different evasion strategies used by parasites to avoid detection by our immune system. The anti-malaria vaccine could be the start of a promising line of new vaccines to tackle parasitic diseases.