A new study reports an improved version of the leading malaria vaccine, RTS,S. Named R21, this next generation vaccine is more immunogenic in lower doses and offers better protection when given alone or in combination with other virus-based malaria vaccines.
Malaria is a significant health problem worldwide. An estimated 214 million new infections, leading to 438,000 deaths were reported in 2015 alone. Moreover, drug-resistant parasites and insecticide-resistant mosquitoes are on the rise. The development of a highly effective vaccine, or improving upon the one already in use, would be crucial in bringing down the global morbidity rate associated with the infection.
Approved by European regulators in 2015, RTS,S remains the sole anti-malarial vaccine on the market to date. Developed by GlaxoSmithKline in collaboration with Walter Reed Army Institute of Research (WRAIR), it is a vaccine made from a subunit of P. falciparum, called the circumsporozoite protein (CSP). To make CSP more immunogenic (and hence more effective), RTS,S uses the hepatitis B surface antigen (HBsAg) as a platform to form 22 nm particles that display CSP on the surface. Once inside the body, immune cells recognize the CSP as foreign and mount an immune response. Further encounters with the same antigen (such as during an infection) elicit an immune response to destroy the P. falciparum sporozoite before it can spread to the liver cells.
Although considered a milestone in the field of malaria prevention, the protective efficacy of RTS,S remains modest (26-50%). Furthermore, for it to remain potent, multiple follow-up doses are required, and efficacy is often low in infants and children.
Researchers at the University of Oxford, UK, now report an improved version of RTS,S, called R21. It was generated by expressing a single CSP-HBsAg fusion protein. It readily formed virus-like particles when expressed in yeast, without the need for additional HBsAg, thereby improving the CSP: HBsAg ratio from 1:4 (as was in RTS,S) to 1:1. This means that on a per particle basis, more CSP antigen is represented on the surface by R21 which may lead to a better immune response against the antigen.
Indeed, a very low dose of R21 showed excellent anti-CSP titers and offered enhanced protection in a rodent model challenged with transgenic CSP expressing sporozoites.
Furthermore, as part of a multi-component vaccine strategy, R21 was combined with other TRAP-protein based viral vaccine. This led to further enhancement of efficacy and better protection against sporozoite infection.
The study is published in the journal Scientific Reports, under Nature Publishing Group.
Written By: Debapriya Dutta, PhD