New malaria vaccine
Background:
- Nearly 600,000 people per year in sub-Saharan Africa die of malaria, a devastating disease that primarily affects young children under the age of five.
- Priority should be given to developing a disease-preventing vaccine, however due to the parasite’s complex life cycle, it has proven difficult to pinpoint the crucial elements that contribute to protective immunity.
Recent developments in the creation of a malaria vaccine:
- The WHO’s approval of GlaxoSmithKline’s RTS,S/AS01 (Mosquirix) malaria vaccine for use in paediatric immunisation in October 2021 will be a great accomplishment.
- RTS, S/AS01 still has a major positive influence on public health and has the potential to save thousands of lives each year, despite only having a minor reduction in severe malaria cases after four doses given to kids under the age of 5.
- The fact that it took more than 30 years and nearly $700 million to make this advancement emphasises the technical challenges and scientific challenges associated with developing a vaccine to stop a parasite illness like malaria.
- GSK has given Bharat Biotech licence to manufacture Mosquirix, and by 2029, it’s projected that the Hyderabad-based company will be the only one doing so globally.
- But RTS,S/AS01 falls short of the WHO’s own benchmark for the effectiveness of the malaria vaccine, which was set at 75% in 2015.
- In September 2021, phase 1 and phase 2 studies of the R21/Matrix M malaria vaccine, developed by the University of Oxford in the UK, among 450 children in Burkina Faso, revealed a 77% effectiveness rate.
- Early in September 2022, R21/Matrix-M received renewed attention because the findings of a booster dose were published in the journal Lancet Infectious Diseases, demonstrating a high efficacy of 80% was maintained after two years.
How vaccines work:
- The RTS,S, and R21 liver stage parasites share a similar component with the main protein known as sporozoite, which is present on their surface.
- Both also contain the self-assembling protein known as hepatitis B virus surface antigen (HBsAg), which promotes the growth of CSP antigen-fused virus-like particles.
- The main difference between the two vaccines is their HBsAg content. About 20% of the fusion protein is found in RTS, S, with the remaining 80% being the independently produced HBsAg antigen.
- In contrast, R21 is entirely made up of the CSP fusion protein moieties. As a result, a much higher percentage of CSP antigen is visible on the surface of the virus-like particle, greatly boosting the likelihood that the host’s immune system will encounter it.
- Matrix-M, a Novavax-produced adjuvant, is used by R21, while AS01, a GSK-developed adjuvant, is used by RTS, S. (Sweden). Matrix M, a formulation of plant-based saponins, stimulates both antibody and cellular immunological reactions to vaccines.
Phase 3 results are awaited:
- Even though the most recent results of a booster dose of R21 have well-deservedly inspired optimism, the results of a larger phase 3 trial of the vaccine will be eagerly awaited.
- In four African countries, including two where malaria is a year-round concern, R21 is presently undergoing phase 3 studies in infants between the ages of 5 and 36 months.
- The effectiveness and safety of R21 will be investigated in these trials at five sites in Burkina Faso, Kenya, Mali, and Tanzania with the participation of 4,800 kids. By the end of 2023, the initial findings are anticipated.
- It will be necessary to construct the risk-benefit analysis using copious, meticulously gathered safety data. The SARS-CoV-2 experience has served as a reminder that serious side effects won’t be identified until millions of vaccinations have been documented.
Advantages and disadvantages:
- Why, especially in light of the fact that India has a long history of conducting fundamental malaria research and has a large number of well-established malaria research and control facilities, has the country not been more successful in developing vaccines against diseases like malaria?
- There is a critical need in India for the creation of secure and reliable models of human infection control for diseases like malaria and the flu.
- All malaria vaccines under development must go through testing in the safe and dependable Controlled Human Malaria Infection (CHMI) model after completing phase 1 safety investigations. This has been adopted by several European countries, including the UK, Colombia, and Thailand. RTS, S, and R21 were all tested in CHMI prior to completing additional safety and effectiveness field studies.
- Researchers at the International Centre for Genetic Engineering and Biotechnology (ICGEB) in Delhi have conducted phase 1 safety testing on two experimental blood stage malaria vaccines that they created and produced in the country.
- However, it has been challenging to continue the development of these vaccines in India due to the absence of the CHMI paradigm. There needs to be better cooperation between scientific, long-term continuous financial, regulatory, and logistic systems to aid researchers in developing novel vaccines to combat infectious illnesses.
