Ending malaria with multiple vax strategies
Ahistoric moment took place on October 6, 2021 when the World Health Organisation (WHO) recommended a groundbreaking malaria vaccine for children at risk. With more than 30 years in making, RTS,S/AS01 vaccine under the brand name Mosquirix has emerged as the world’s first malaria vaccine.
Developed by the British firm GlaxoSmithKline (GSK), non-profit organisation PATH and with support by Bill & Melinda Gates Foundation, Mosquirix has changed the course of public health history. For a disease that can kill within 24 hours of symptom onset, this development is indeed remarkable.
But the development of this malaria vaccine has faced several obstacles, in terms of lack of a traditional market, few developers, and the technical complexity of developing any vaccine against a parasite since malaria parasites have a complex life cycle, and there is poor understanding of the complex immune response to malaria infection.
Malaria parasites are also genetically complex, producing thousands of potential antigens. Unlike the diseases for which we currently have effective vaccines, exposure to malaria parasites does not confer lifelong protection. Mosquirix has been developed to trigger the immune system to defend against the first stages of malaria when the Plasmodium falciparum parasite enters the human host’s bloodstream through a mosquito bite and infects liver cells. The vaccine is designed to prevent the parasite from infecting the liver, where it can mature, multiply, re enter the bloodstream, and infect red blood cells, which can lead to disease symptoms.
Another promising malaria vaccine candidate is being developed by the US-based biotech company Sanaria since 2010. It includes whole sporozoites, the sexual form of the parasite extracted from mosquito salivary glands, which have either been made noninfectious through irradiation or are administered along with chemoprevention. A more effective vaccine could also come in the form of the University of Oxford’s R21 that recently showed good efficacy in an early trial testing it among children 5- 17 months of age in Burkina Faso, West Africa.
Besides malaria, dengue fever is the next critical mosquito-borne disease in the world that is most rapidly spreading. There has been a 30-fold increase in global incidence over the past 50 years. Although a vaccine (Dengvaxia) has been developed for this disease, the maker Sanofi Pasteur had announced in 2017 that people who receive the vaccine and have not been previously infected with a dengue virus may be at risk of developing severe dengue if they get dengue after being vaccinated.
Developing a viable vaccine against dengue virus has proved difficult over the years because the pathogen is actually four different virus types, or serotypes. Unless a vaccine protects against all four, a vaccine can wind up doing more harm than good.
Preparing tools such as vaccines to fight these diseases appears to be a common strategy, but did you know that these little super-spreader of diseases could actually transform into friends that can be used to inject the vaccine in humans? The story goes back to 2010 when a group of Japanese researchers genetically engineered mosquitoes that spread vaccines instead of disease. For their study, the researchers attached SP15 vaccine against leishmaniasis, a parasitic disease spread by sand flies that can cause skin sores and organ damage, to a malaria mosquito. These mosquitoes produced SP15 in their saliva, and mice bitten by these mosquitoes produced antibodies against the parasite. However, the team wasn’t sure whether the immune response was strong enough to protect against infection.
Adding to it, the concept of a ‘flying vaccinator’ transgenic mosquito is not likely to be a practicable method of disease control, because a ‘flying vaccinator’ is an unacceptable way to deliver vaccines without dosage limit and informed consent against current vaccine programmes.
With vaccines emerging as the most effective solution to prevent a large number of deadly diseases globally, we might just end up using flying vaccinecarrying syringes, marking another historic event.