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Malaria vaccine phase II trial results shows record efficacy

A new malaria vaccine candidate R21/MM surpasses the efficacy (77%) of the previous Mosquirix vaccine (55%) in early trials. 

Malaria is mainly caused by a parasite called Plasmodium falciparum and claims around 4,05,500 lives annually. The female Anopheles mosquito injects the parasite from its saliva into the bloodstream in the form of a sporozoite. The sporozoites form merozoites in the hepatocytes completing half of its cycle. These merozoites invade the red blood cells and produce more merozoites until the cells burst open, thus beginning a new infective cycle.

P. falciparum, over time, has developed mechanisms to evade immune reactions and become resistant to drugs. Thus, making it challenging to develop a vaccine and formulate possible treatments. The malaria vaccine currently available is RTS,S/AS01 aka Mosquirix and was developed by GlaxoSmithKline in the late 1980s. This vaccine has parts of the circumsporozoite protein (CSP) which is found in sporozoites, thus inducing appropriate immune response and memory antibodies. The efficacy of Mosquirix ranges from 26% to 55% in infants. The pilot implementation of the Mosquirix vaccine was approved by the WHO in 2015 and was launched all across Africa in 2019. 

However, Mosquirix does not meet the WHO’s mandate of 75% efficacy for a vaccine. A new hope came in the form of the R21/MM candidate vaccine. Developed by the scientists at the University of Oxford’s Jenner Institute along with Novavax and Serum Institute of India, the vaccine showed 77% efficacy in its phase IIb trials. The trials were conducted in a cohort of 450 children ageing between 5-17 months from Burkina Faso, West Africa and the results were published in The Lancet

R21 is a pre-erythrocytic vaccine and is similar to Mosquirix. Both vaccines have HBsAg (hepatitis B virus antigen) fused to the antigenic parts of CSP and form spherical ‘virus-like particles’. R21 has a lesser amount of the HBsAg exposing more of the CSP antigen as compared to RTS/AS01 vaccine. Hence, only a small quantity of R21 was enough to induce stronger and long-lasting immune responses. An adjuvant is a high molecular weight substance that is given along with the vaccine to boost its immunogenicity. R21 along with Matrix-M (MM), saponin-based adjuvant elicits an effective humoral and cell-mediated response. In phase I and IIa clinical trials, the vaccine showed a good immunogenic profile in mice. 

The trial cohort was divided into 3 groups of 150. Group A received 5ugR21/25ugMM vaccine, group B received 5ugR21/50ug MM and group C received a rabies vaccine. The vaccine was administered through the intramuscular route. Three doses over a span of three weeks were administered before the seasonal malaria peak in July and a fourth shot was given 12 months later. The primary outcome was to check the protective efficacy of the vaccine against clinical malaria 28 days from the third shot up to 6 months.  

After 6 months, 43 children from Group A, 38 children from Group B and 105 children from Group C had clinical malaria showing 71% efficacy of the vaccine in group A and 77% efficacy in group B. The efficacies remained the same during the 12-month checkup as well. The first two groups also had a high titre of antibodies (86% increase) against the NANP central repeats of the CSP antigen in the vaccine within 28 days of receiving the third shot. The antibody titre levels reduced over the following 12 months but returned after receiving the fourth vaccination. 

Another advantage of the R21/MM vaccine is the ease and low cost of production. Only 5ug of R21 is required and the MM adjuvant is less complex to manufacture, which can allow for a large scale supply of the vaccine. Further phase III trials involving a larger cohort is required to further confirm the effectiveness of the R21/MM vaccine. This study gave rise to the very first malaria vaccine to cross the WHO mandate of 75% efficacy and provides exciting prospects of a prophylactic solution to eradicate the deadly parasitic disease. 

“A phase 3 trial across five African sites of differing malaria transmission and seasonality is underway, with the aim of licensure of a safe, low-cost, high efficacy vaccine, which can substantially reduce the malaria disease burden,” the scientists postulate.

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