Malaria, New Malaria Vaccine R21/MatrixM

Context (TH | TH | IE | FP | WIRE): The WHO recommended (but yet to be prequalified) a malaria vaccine, R21/MatrixM.

Established in 2001, WHO Prequalification ensure that medicines supplied by procurement agencies (like UNICEF, UNITAID, etc.) meet quality, safety and efficacy standards.

Malaria

Malaria is a mosquito-borne infectious disease that affects humans and other animals.
It is caused by single-celled microorganisms of the Plasmodium group of protozoans (microscopic heterotrophs that live as predators or parasites).

Five Plasmodium species cause malaria in humans.
- Plasmodium falciparum and Plasmodium vivax pose the greatest threat.
- Recent evidence has shown drug-resistant mutations in Plasmodium Falciparum.
- P. ovale and P. malariae generally cause a milder form of malaria.
- P. knowlesi rarely causes disease in humans.
Transmission: Infected female Anopheles mosquitoes transmit Plasmodium parasites through bites. The parasites multiply in the liver and destroy red blood cells (RBCs).
Symptoms: Fever, chills, yellow skin, seizures etc.
Treatment: It is preventable as well as curable. Prevention of malaria includes medications and mosquito elimination.
Distribution: It is mostly found in tropical and subtropical areas of Africa, Asia, and South America.

Currently, none of the two malaria vaccines is approved to be used in India.

According to WHO, in 2021, worldwide there were 247 million malaria cases and 6,19,000 deaths.
African Region accounted for 95% of all malaria cases and 96% of all malaria deaths in 2021.
Children under age five accounted for about 80% of all malaria deaths in the African Region.
Moreover, 25 million children are born yearly in countries with moderate to high malaria transmission.

It is the world’s second WHO-recommended malaria vaccine for children, after RTS,S in 2021.
It is developed by Oxford University and manufactured by the Serum Institute of India (SII).
The new vaccine will be sold under the brand Mosquirix.
It has been approved for use in Burkina Faso, Ghana, and Nigeria for children under 36 months.
This vaccine is meant for children under the age of five years
It has three primary doses and a booster shot after a year.
It is specific to Plasmodium falciparum. So, it cannot be used to prevent infections caused by other malaria parasites like Plasmodium vivax.
It uses the same adjuvant, Matrix M, as the COVID-19 vaccine, Novavax, a version of which was also rolled out by SII.

Adjuvant: A substance that is added to a vaccine to enhance the immune response to the vaccine.
Matrix M: It is a proprietary saponin-based adjuvant from Novavax, licensed to the SII for use in endemic countries, while Novavax retains commercial rights in non-endemic countries.

High efficacy: It has an efficacy of 75% in areas with seasonal prevalence and 68% in areas where the disease circulates all year round.
Low cost: It is about half the price of RTS,S, the only other malaria vaccine available.
Mass production: Serum Institute of India has the potential to mass-produce it on a large scale.

The vaccine efficacy was maintained for 18 months, with a single booster dose given 12 months after the primary series.
Efficacy is higher in younger children (5-17 months) than older ones (18-36 months), suggesting potential lower effectiveness in those previously exposed to malaria.
Also, the vaccine was more efficacious in seasonal malaria areas than in perennial ones. This suggests the vaccine will be not highly effective for children in areas with very high malaria incidence.

Vaccines are designed to stimulate the immune system against specific infectious diseases.
Both the newly endorsed malaria vaccines, R21 and RTS,S, are sub-unit vaccines that aim to protect against malaria caused by Plasmodium falciparum parasite.
They contain the circumsporozoite protein, which coats the surface of the P. falciparum parasite.
The protein on the vaccines triggers an immune response against the P. falciparum parasite
It’s a bit like how most COVID vaccines target the “spike” protein on the surface of SARS-CoV-2 (the virus that causes COVID) to block the virus.

Sub-unit Vaccine is a type of vaccine that contains only a portion of the pathogen (such as a protein or antigen) rather than the whole microorganism.

Both malaria vaccines are administered with an adjuvant and contain the same parasite protein target, but they are designed with different amounts of parasite protein and unique adjuvants.

Administration of booster shots: The trials show that yearly boosters will be required to maintain protection. But boosters are challenging to administer even in areas with robust health systems.
Non-integration with children vaccination programmes: To date, neither malaria vaccine has been integrated into other childhood vaccination programs, placing an additional burden on communities.
Very high malaria-risk areas: There is a risk that previous malaria infection can block the efficacy of vaccines, leaving those most at risk with reduced protection.

Context (TH): Both the endorsed malaria vaccines does not target the malaria in India which is caused by Plasmodium vivax parasites.

They target only the malaria caused by Plasmodium falciparum parasites which is the deadliest.

India saw an 85.1% decrease in malaria cases and an 83.36% drop in deaths from 2015 to 2022.
However, according to the WHO, India accounts for 83% of malaria cases in southeast Asia.
India is now in a lower-endemic area, reporting fewer than 100 deaths in the last two to three years.

Before rolling out any vaccine or any programme, we must do a cost-benefit analysis.
WHO has done this assessment only in high burden countries where vaccine is cost-effective.
In low-burden countries like India, vaccination is not very cost-effective.
Moreover, Plasmodium Vivax is not a very severe variant.

Many countries like Sri Lanka, Maldives and China, which were high burden countries, eliminated malaria only by control measures.
There are various control measures under the National Vector Disease Control programme need to be accelerated.

Both endorsed vaccines only target one type of malaria, that is, caused by P. falciparum parasites. It’s the deadliest form of malaria, so vaccine efforts have primarily targeted this species.
These vaccines don’t protect against other malaria types, esp. P. vivax, a major concern in SE Asia.
So, it is essential to develop second-generation malaria vaccines, which can:
- Induce high levels of sustained protection without the need for yearly boosters
- Protect against all malaria types (particularly P. vivax)
- Protect children who have the highest malaria risk