Mosquirix™ RTS, S/AS01 Vaccine Development, Immunogenicity, and Efficacy

Abstract

Malaria is a parasitic infection caused by bites from Plasmodium falciparum (P.falciparum)-infected mosquitoes with a present scale of symptoms ranging from moderate fever to neurological disorders. P. falciparum is the most lethal of the five strains of malaria, and is a major case of morbidity and mortality in endemic regions. Recent advancements in malaria diagnostic tools and prevention strategies have improved conjugation antimalarial therapies using fumigation and long-lasting insecticidal sprays, thus lowering malarial infections. Declines in the total number of infected individuals have been correlated with antimalarial drugs. Despite this, malaria remains a major health threat, affecting more than 30 million men, women, and children around the globe, and 20 percent of all children around the globe have malaria parasites in their blood. To overcome this life-threatening condition, novel therapeutic strategies, including immunization, are urgently needed to tackle this infection around the world. In line with this, the development of the RTS, S vaccine was a significant step forward in the fight against malaria. RTS, S is a vaccine for P. falciparum in which R specifies central repeat units, T the T-cell epitopes, and S indicates surface antigen. The RTS, S/AS01 malarial vaccine was synthesized and screened in several clinical trials between 2009 and 2014, involving thousands of young children in seven African countries, showing that children who received the vaccine did not suffer from severe malaria. Mosquirix™ was approved by the World Health Organization in 2021, indicating it to be safe and advocating its integration into routine immunization programs and existing malaria control measures. This paper examines the various stages of the vaccine’s development, including the evaluation of its immunogenicity and efficacy on the basis of a total of 2.3 million administered doses through a routine immunization program. The protection and effectiveness provided by the vaccine are strong, and evidence shows that it can be effectively delivered through the routine child immunization platform. The economic cost of the vaccine remains to be considered.

Advances in Infectious Disease Vaccine Adjuvants

“…The Walter Reed Army Institute of Research (WRAIR) and GSK developed the RTS, S malarial vaccine in 1987 [ 291 ]. The ‘R’ in RTS, S vaccine represents the central repeat region, made up of the chain of N-acylneuraminate-9-phosphate (NANP) amino acid tandem repeat tetrapeptides.…”

“…The ‘R’ in RTS, S vaccine represents the central repeat region, made up of the chain of N-acylneuraminate-9-phosphate (NANP) amino acid tandem repeat tetrapeptides. ‘T’ represents the immune dominant segregated epitopes of T lymphocytes, and ‘S’ is the surface antigen of Hepatitis B [ 291 ]. This RTS, S malaria vaccine contains the circumsporozoite protein and an adjuvant system (AS01 and AS02) and was clinically assessed in children and infants [ 148 ].…”

“…RTS, S/AS01 combined with a plasmodium subunit antigen was shown to secrete antigen-specific immunoglobulins and CD4 + cells, with the stimulation of both cell-mediated and antibody immune responses, effectively blocking sporozoite colonisation of hepatocytes and protecting against new, P. falciparum [ 291 ]. However, Phase 3 clinical trials of this RTS, S/AS01 malaria vaccine did not provide sufficient protection due to passage of time [ 291 ].…”

“…RTS, S/AS01 combined with a plasmodium subunit antigen was shown to secrete antigen-specific immunoglobulins and CD4 + cells, with the stimulation of both cell-mediated and antibody immune responses, effectively blocking sporozoite colonisation of hepatocytes and protecting against new, P. falciparum [ 291 ]. However, Phase 3 clinical trials of this RTS, S/AS01 malaria vaccine did not provide sufficient protection due to passage of time [ 291 ]. Further, potential safety risks occurred in the young-testing group, [ 291 ] meaning further optimisation of the RTS, S/AS01 malaria vaccine to focus on the prolonged immunogenicity and elimination of the safety problems in children is necessary [ 291 ].…”

“…However, Phase 3 clinical trials of this RTS, S/AS01 malaria vaccine did not provide sufficient protection due to passage of time [ 291 ]. Further, potential safety risks occurred in the young-testing group, [ 291 ] meaning further optimisation of the RTS, S/AS01 malaria vaccine to focus on the prolonged immunogenicity and elimination of the safety problems in children is necessary [ 291 ].…”