Analysis: scientists face a number of hurdles and drawbacks when it comes to developing effective vaccines for diseases like malaria
Never in the 200-year history of immunisation has a vaccine (let alone several) been developed and approved for wide-scale use in such a short amount of time as with Covid-19. So why haven't we been able to unleash the power of vaccines – and a similar shared sense of purpose – against the deadliest disease in human history?
Since the foundations were laid in the fight against smallpox in the 1790s, vaccines have been integral to our ability to control, prevent and eliminate various diseases. However, scientists have so far failed to produce effective vaccines against diseases caused by parasites. Parasites are a range of organisms that live on or in other organisms (hosts) and extract nutrients from them.
Malaria is the most deadly disease in human history, with over 229 million cases and 409,000 deaths in 2019 alone. Over 65% of malaria deaths occur in children under the age of five. Despite these staggering figures, and the efforts of scientists worldwide, there is no widely-available vaccine against the parasite Plasmodium falciparum, which is responsible for the majority of human malaria cases in Africa and Southeast Asia.
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From RTÉ Radio 1's News At One, Dr William Hamilton from the Wellcome Sanger Institute on a study which has found that malaria parasites resistant to key drugs are spreading rapidly in South East Asia
Parasites don’t just cause deaths but contribute to reduced quality of life, impaired cognitive development and severe disfigurement, primarily in the world’s poorest people. They also cause diseases in livestock, domestic pets and wildlife worldwide. In 2020, the economic impact of the pandemic was expected to exceed the combined cost of every natural disaster in the previous 20 years. The economic impact of diseases caused by infection with parasites might not be as obvious. Still, the annual cost of worms on livestock production in the EU alone is estimated to be more than €1.8 billion.
Controlling diseases caused by the major parasites relies on the delivery of drug treatments to people in endemic areas. But as is the case with the emergence of anti-microbial resistance in our fight against bacterial infections, parasites that are resistant or less susceptible to these drugs are rapidly emerging and spreading. Hence, the clock is ticking as the limited number of anti-parasitic drugs available lose their potency. Even worse, residues from these drugs are increasingly detected in the environment, with the negative effects on the biodiversity of essential insect populations just starting to be quantified.
So what’s the hold up? If parasites are such a problem, why do we still not have any widely-available vaccines for the diseases they cause? The first issue is because most parasites infect at least one host to complete their life cycle, making them far more difficult (and expensive) to study in the laboratory than bacteria and viruses. Secondly, they also come in great variety, from the simple, consisting of only one cell, to the complex, which have many cells.
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From RTÉ Radio 1's Liveline, listener Ronan Fahey talks about taking part in a clinical trial for a new malaria vaccination
The third hurdle is the enormous complexity of multicellular parasites, many of which are capable of intricate interactions with their hosts – including deliberately manipulating or suppressing host immune responses to ensure their survival. Most people are aware by now that the vaccines used to protect against Covid-19 target the spike protein that the virus uses to attach and infect human cells. This protein, which is one of only 29 produced by SARS-CoV-2, is an ideal vaccine target because it prevents the virus from binding to host cells, stopping it in its tracks.
However, most multicellular parasites have much larger genomes than viruses and bacteria and thus make a lot more proteins. Some parasite genomes contain up to 22,000 genes, many of which encode proteins that help them infect and cause disease in their hosts. For example, our 'friend’ Plasmodium falciparum, has about 5,300 genes. It quickly becomes apparent that scientists working to develop vaccines against diseases caused by parasites have much more work to do to identify ideal parasite vaccine targets.
Scientists have tried to circumvent this complexity by creating vaccines that use whole parasites specifically treated to prevent disease, while still generating protective immune responses in vaccinated hosts. This approach avoids the need to identify individual target proteins, but the major drawback is the need to produce these parasites in the laboratory – which is logistically impossible for large-scale vaccine production.
here parasites are concerned, vaccine hesitancy is further exacerbated by their general 'ick factor'
Unfortunately, as we have seen with many other vaccines, it can often be difficult to convince the general public to adopt killed or inactivated vaccines. Where parasites are concerned, vaccine hesitancy is further exacerbated by their general ‘ick factor’. People are often unwilling to be exposed to parasites (dead or alive), even if it prevents against much more severe disease in the future.
Thankfully, the successful Covid-19 vaccine effort has opened up a new world of possibilities for vaccine research that is likely to have profound impacts across other diseases – including those caused by parasites. Aside from highlighting the potential of mRNA vaccine technology as a new means of vaccination, the global Covid-19 vaccine response has streamlined our ability to manufacture and distribute vaccines, and has alerted the general public and policy-makers alike of the major risks imposed by infectious diseases. Hopefully, innovation in these fields will translate across to parasite vaccine research, enabling the adoption of new vaccine technologies for both production and public uptake.
The views expressed here are those of the author and do not represent or reflect the views of RTÉ
