Systematic Review of Safety of RTS,S with AS01 and AS02 Adjuvant Systems Using Data from Randomized Controlled Trials in Infants, Children, and Adults

Abstract

Background: Emergence of antimalarial drugs and insecticides resistance alarms scientists to develop a safe and effective malaria vaccine. A pre-erythrocytic malaria vaccine called RTS,S has made great strides. Aim: The review was aimed to assess the safety of the candidate malaria vaccine RTS,S with AS01 and AS02 adjuvants using data from Phase I-III randomized controlled clinical trials (RCTs). Methods: This systematic review was conducted based on PRISMA 2020. Regardless of time of publication year, all articles related with safety of RTS,S, RCTs published in the English language were included in the study. The last search of databases, and registry was conducted on 30 May, 2022. Pubmed, Google Scholar, Cochrane Library, Wiley Online Library, and Clinical trials.gov were thoroughly searched for accessible RCTs on the safety of RTS,S malaria vaccine. The studies were screened in three steps: duplicate removal, title and abstract screening, and full-text review. The included studies' bias risk was assessed using the Cochrane risk of bias tool for RCTs. This systematic review is registered at Prospero (registration number: CRD42021285888). The qualitative descriptive findings from the included published studies were reported stratified by clinical trial phases. Findings: A total of thirty-five eligible safety studies were identified. Injection site pain and swelling, febrile convulsion, fever, headache, meningitis, fatigue, gastroenteritis, myalgia, pneumonia, reactogenicity, and anemia were the most commonly reported adverse events. Despite few clinical trials reported serious adverse events, none of them were related to vaccination. Conclusion: Most of the adverse events observed from RTS,S/AS01 and RTS,S/AS02 malaria vaccines were reported in the control group and shared by other vaccines. Hence, the authors concluded that both RTS,S/AS01 and RTS,S/AS02 malaria vaccines are safe.

Frequency of serious adverse events and death in 5-17 months children receiving RTS,S/AS01E vaccine - a systematic review and meta-analysis of RCTs.

“…SAEs refer to signi cant, severe, or life-threatening medical occurrences or conditions that participants may experience after receiving the vaccine. These events go beyond the expected side effects and pose a substantial risk to the health and well-being of the individuals involved [19].…”

Recent Advances in Messenger Ribonucleic Acid (mRNA) Vaccines and Their Delivery Systems: A Review

“…Most of the adverse events observed from mRNA vaccines were also reported from RTS, S malaria vaccine, and other vaccines were also shared by other vaccines. 356 Therefore, as far as mRNA vaccines are the current choice of vaccine development, further research is required to optimize the in vitro transcribed RNA vaccine and delivery materials, notably lipid nanoparticles, to address the aforementioned difficulties. Use of biodegradable lipids, changing (optimization) of the four components of LNPs, use of effective purification techniques, chemical modifications to the mRNA molecule, such as cap structures and modified nucleosides, choice of appropriate delivery materials, use of cryoprotectants and lyophilization technique, and appropriate implementation of cold chain requirements of mRNA vaccines are among the strategies to increase the effectiveness of mRNA vaccines.…”