RTS, S (also: RTS, S / AS01, trade name: Mosquirix) - mRNA vaccine against malaria produced by GlaxoSmithKline and Bharat Biotech. The first ever vaccine against this disease and the first vaccine against the parasite. Given in 4 doses, it provides only partial, temporary protection against infection in children over 5 months of age. The vaccine is not intended for sale in malaria-free areas.
History of the creation
Vaccine research has been conducted since 1984 by GlaxoSmithKline (GSK) and the Walter Reed Army Institute of Research (WRAIR). Both institutions tried to create a vaccine that exploited the finding that ionizing radiation attenuated sporozoites prevent malaria infection (another vaccine candidate uses them: PfSPZ). CSP, a circumsporozoite protein, was identified as the target protein of the immune response. WRAIR and the US National Institutes of Health have successfully duplicated and sequenced this protein. Since the production of the entire CSP antigen was very difficult at the time, GSK used Escherichia coli to produce the antigen fragments (central repeat region). One of the four candidate antigens was submitted to clinical trials. In controlled infection, one volunteer showed a protective effect. However, multiple attempts to create a vaccine using only the CSP fragment have not yielded clinically significant results. Since 1987, GSK and WRAIR have worked together.
GSK researchers, using the knowledge gained from the development of the Energix-B hepatitis B vaccine, pioneered the use of HBV surface antigens as a carrier of the central repeat region and the C-terminal region of the CSP protein (containing the T and B epitopes) of the NF54 strain Plasmodium falciparum. As a result, the presentation of the antigen to the immune system was enhanced.
Then, attempts were made to select an appropriate vaccine adjuvant. Ultimately, GSK and WRAIR selected AS01 as the best. It contains immunostimulants 3-O-deacylated 4ʹ-monophosphoryl lipid A (MPL) and saponins QS-21 (obtained from the true soapwood) based on liposomes.
Since 2001, GSK has been working on it with PATH (Program for Appropriate Technology in Health) as part of a public-private partnership, using funding from the Bill & Melinda Gates Foundation.
Phase III clinical trials
Phase III clinical trials lasted from 2009 to 2014. It was attended by 15,459 children and infants and 11 clinical centers in 7 countries (Burkina Faso, Gabon, Ghana, Kenya, Malawi, Mozambique, Tanzania), including 8,922 patients aged 5-17 months and 6,537 infants aged 6-7. 12 weeks. In the double-blind study, participants were randomly assigned to one of three equal groups:
the first received three doses of RTS, S / AS01 at 0, 1 and 2 months and a booster dose after 20 months.
the second three doses of RTS, S / AS01 at 0, 1 and 2 months, after 20 months vaccination against meningococcus C (Menjugate agent).
the third, comparative, received 3 doses of rabies vaccination (Verorab) and the fourth dose of meningococcal vaccination (as above), at the same time schedule: 0, 1, 2, and 20 months. The results showed that giving 4 doses of vaccine prevented in four From the age of 39, 39% of infections and 29% of severe disease. It killed 1,774 cases of malaria per 1,000 vaccinated children (infection may occur multiple times). The effectiveness of the vaccine declines over time and further studies with booster doses are required.
Vaccination adverse reactions were similar to other routine vaccinations in this age group. Febrile seizures were more common in children 5-17 months of age, especially after the 3rd dose of that