Explained: Why It Took Over 3 Decades To Develop a Vaccine for Malaria?

Experts and research highlight the hindrances faced during developing a vaccine for malaria parasite, which has a complex life cycle

Update: 2021-10-09 13:45 GMT


The World Health Organization (WHO), on October 6, 2021, approved the first vaccine against malaria after a nearly seven decade global battle against the disease which claims lives of more than four lakh people each year. The WHO has recommended a widespread deployment of the vaccine — RTS,S/AS01, which is developed by GlaxoSmithKline (GSK) for children below five years in sub-Saharan Africa and other at-risk regions.

"This is a historic moment. The long-awaited malaria vaccine for children is a breakthrough for science, child health and malaria control," said WHO Director-General Dr Tedros Adhanom Ghebreyesus. According to him, "Using this vaccine on top of existing tools to prevent malaria could save tens of thousands of young lives each year."

However, it is to be noted that RTS,S is a vaccine that acts only against one species of the Plasmodium parasite known as the Plasmodium falciparum (the deadliest malaria parasite globally and the most prevalent one in Africa). The vaccine offers no protection against the other four species such as P. vivax, P. ovale, P. knowlesi and P. malariae which are prevalent in South-East Asia, Americas and Europe.

According to WHO's World Malaria Report 2020, the WHO African region accounted for 94% of malaria cases in 2019 carrying the highest share of the global malaria burden. In 2018, the species P. falciparum accounted for 99.7% of estimated malaria cases in the WHO African Region, while the Eastern Mediterranean region saw 71% of cases, Western Pacific (65%) and the South-East Asia region, 50%.

About 95% of malaria deaths globally were in 31 countries, highlighted the report. Nigeria (23%), the Democratic Republic of the Congo (11%), the United Republic of Tanzania (5%), Mozambique (4%), Niger (4%) and Burkina Faso (4%) accounted for about 51% of all malaria deaths globally in 2019.

What is the RTS,S vaccine?

The making of the plasmodium falciparum candidate, RTS,S, brand name Mosquirix, dates back to the late 20th century. The first trials of this vaccine were published in 1997, after which a series of trials culminated in phase 3 testing (conducted over five years—2009-2014) and was later favourably reviewed in 2015 by the European Medicines Agency, as per a June 2020 article titled Malaria vaccines since 2000: progress, priorities, products in Nature journal.

After a thorough review of the phase 3 trial results, two independent WHO advisory groups — the Strategic Advisory Group of Experts on Immunization and the Malaria Policy Advisory Group — jointly called for pilot implementation of the vaccine in three to five settings in sub-Saharan Africa, according to the WHO.

The current approval of the vaccine is based on the results of the ongoing pilot programme in Ghana, Kenya and Malawi, where the vaccine has reached more than eight lakh children since 2019. The findings show that the vaccine, which requires four injections, thwarted about 4 in 10 (39%) cases of malaria over four years of follow-up and about 3 in 10 (29%) cases of severe malaria, with significant reductions seen in overall hospital admissions as well as in admissions due to malaria or severe anaemia.

Moreover, the vaccine also reduced the need for blood transfusions, which are required to treat life-threatening malaria anaemia by 29%, according to the WHO. RTS,S is a recombinant protein vaccine.

"The reason it is called RTS,S is because S is coming from the surface protein of Hepatitis and it is a very good carrier for another protein when you want to stimulate the antigens," Dr Virander Chauhan, an Arturo Falaschi Emeritus Scientist at the International Centre for Genetic Engineering and Biotechnology, told FactChecker. He is best known for his contribution in developing procedures to prepare recombinant vaccine target antigens.

Malaria in India

Cases and deaths related to malaria have steadily reduced in the last five years from more than 10.87 lakh cases and 331 deaths in 2016 to more than 28,000 cases and 18 deaths as of June 2021, according to a Lok Sabha response in July 2021. "In 2020, 99.97% of malaria cases were reported to have recovered after treatment. The number of malaria cases and deaths has been constantly declining in the country. There is 84.4% reduction in malaria cases and 83.6% reduction in malaria deaths in 2020 as compared to 2015," read the LS response.

Malaria is mainly present in the eastern and central part of India. According to the WHO, India accounted for about 86% of all malaria deaths in the WHO South-East Asia Region in 2019.

With 10,347 cases, Chhattisgarh has the highest number of malaria cases in the first five months of 2021. It is followed by Odisha with 6,260 cases and Jharkhand with 3,436 cases. Chhattisgarh (14) saw the highest number of deaths caused by the vector borne disease, followed by Maharashtra and Odisha with two deaths each.

Malaria Vaccine: Why It Took So Long to Develop?

Malaria is caused by infestation rather than an infection of red blood cells by a protozoan parasite generally called malarial parasite, which is the term applied for invasion by microbes (viruses and bacteria).

Health experts FactChecker spoke to said there are various factors that hindered the development of the vaccine with the main factor being the complex life cycle of the malarial parasite. "A mosquito is a definitive host (with sexual reproduction/ multiplication) and human the intermediate host (having asexual stages)," Dr T Jacob John, virologist and professor emeritus of Christian Medical College, Vellore, told FactChecker.

"The antigens of the two stages are very complex and immunity to no one antigen offers protection. The immune protection against viruses and bacteria is relatively good, but against protozoa, relatively poor. Many attempts to design a safe and effective malaria vaccine had failed. That is the reason for the enormous delay in approving a vaccine now, in spite of the fact that the approved vaccine is not highly protective," said John.

The mosquito carrying P. falciparum, responsible for the most severe form of malaria, injects a form of parasite called sporozoite into the bloodstream of a person, according to an article on Building a better Malaria Vaccine in Nature. These sporozoites infiltrate the liver and multiply while later hijacking the red blood cells. It is important that the vaccine, RTS,S targets these sporozoites before they reach the liver.

"The question that comes in the public's mind is that it took less than a year to develop the COVID-19 vaccine and nearly 30 years to make a vaccine for malaria. COVID-19 is an exception because its genomes are very small. They don't multiply on their own. If a virus can have 12-15 proteins a malaria parasite will have as many as 5,000 proteins," explained Chauhan.

Firstly, when it comes to viruses, it ideally takes five to six years to develop a vaccine because virus genomes are small in number. "Even for Hepatitis A and B, vaccines took at least 10 years. We still do not have an HIV vaccine. There are vaccines against viruses and even bacteria, but this is a first for parasites," he added.

Secondly, AS01 in the vaccine is an adjuvant. An adjuvant is a chemical that boosts your ability to make an immune response. In the case of this vaccine, the adjuvant took a very long time to discover.

Thirdly, most of these vaccines will be administered to children below the age of five. Safety trials cannot begin in this age group without first conducting trials on adults. Even for COVID-19, the vaccines were first administered to adults, while trials for children are still under process.

"We need a series of safety and efficacy trials which take years. It has taken nearly 17 years to conduct phase 2 and 3 trials. Still, what we have is not efficacious. The efficacy of the vaccine is only 39% which means the effectiveness will wane off within 3-4 years," said Chauhan.

India close to eradicating malaria?

So far, no district or state in the country has been declared malaria free. However, in 2020, total 116 districts reported zero malaria cases and 215 districts reported less than 10 cases, said Minister of State for Health & Family Welfare Dr Bharati Pravin Pawar in a response given in the Lok Sabha on July 23, 2021.

"India does not have a functional Health Protection Agency, for which reason we have special programmes against single diseases like malaria, tuberculosis, polio, leprosy, AIDS. But not against all other diseases like typhoid, cholera, scrub typhus, leptospirosis, amebic dysentery, shigella dysentery, hookworm, cysticercosis and so on," said John.

The Centre has launched the National Framework for Malaria Elimination, 2016-2030 to eliminate malaria in India. The goal is to achieve zero indigenous cases of Malaria in the country by 2027 and get 'malaria free' certification by 2030.

The ideal efficacy or protection of the vaccine should be over 65%, according to the National Malaria Control Programme. This means that the current vaccine can only partially protect a person.

The vaccine was developed by GSK Laboratories, and its field investigations were supported by PATH. In January 2021, GSK and PATH chose Bharat Biotech International Ltd (BBIL) as a manufacturing partner, after an international competitive selection process to ensure long-term supply of the RTS,S vaccine.

"Specific studies will have to be done to see if RTS,S vaccine will have a role in malaria control in endemic regions in India," John said while adding that India has more Vivax malaria than Falciparum so this vaccine may not prove to be very helpful in India's goal to eradicate malaria.



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