• Vaccine Name: RTS,S/AS02A
• Target Pathogen: Plasmodium spp.
• Target Disease: Malaria
• Vaccine Ontology ID: VO_0000774
• Type: Subunit vaccine
• Status: Clinical trial
• Antigen: RTS,S is the pre-erythrocyte sporozoite-stage Plasmodium falciparum antigen. It is a circumsporozoite surface protein (Alonso et al., 2004).
• Adjuvant:
  • Adjuvant name:
  • VO adjuvant ID: VO_0001264
• Preparation: RTS,S/AS02 is a pre-erythrocyte sporozoite-stage malaria vaccine based on the circumsporozoite surface protein of Plasmodium falciparum RTS,S fused to HBsAg , incorporating a new adjuvant (AS02) (Bojang et al., 2001; Alonso et al., 2004).

Human Response

• Host Strain: Mozambique children
• Vaccination Protocol: A double-blind, phase IIb, randomised controlled trial was performed in Mozambique in 2022 children aged 1–4 years. The study included two cohorts of children living in two separate areas which underwent different follow-up schemes. Participants were randomly allocated three doses of either RTS,S/AS02A candidate malaria vaccine or control vaccines. The primary endpoint, determined in cohort 1 (n=1605), was time to first clinical episode of P falciparum malaria (axillary temperature ≥37·5°C and P falciparum asexual parasitaemia >2500 per μL) over a 6-month surveillance period. Efficacy for prevention of new infections was determined in cohort 2 (n=417) (Alonso et al., 2004).
• Persistence: Vaccine efficacy in extending time to first infection was determined in cohort 2. 323 children had first episodes of asexual P falciparum parasitaemia (157 in the RTS,S/AS02A group and 166 in the control group), yielding a vaccine efficacy estimate of 45.0% (95% CI 31.4–55.9; p<0.0001). The mean density of asexual-stage parasites at the time of first infection was similar for the control and RTS,S/AS02A groups (3950 vs 3016 per μL, p=0.354). With the same methods as those used to assess persistence of efficacy for cohort 1, the model with the best fit suggested waning efficacy of the vaccine over time, which stabilised at about 40%. The prevalence of asexual P falciparum parasitaemia at the end of follow-up was lower in the RTS,S/AS02A group than in the control group (52.3% vs 65.8%; p=0.019), and prevalence of anaemia at month 8·5 was 2.7% in the control group and 0% in the RTS,S/AS02A group (p=0.056) (Alonso et al., 2004).
• Immune Response: Prevaccination anti-circumsporozoite antibody titres were low in the study children. The vaccine was immunogenic, inducing specific antibody levels after dose three, decaying over 6 months to about a quarter of the initial level, but remaining well above baseline values. Antibody levels in the control group remained low over the follow-up period. The vaccine also induced high levels of antibodies against HBsAg (>97% seroprotection). For both circumsporozoite and HBsAg, immunogenicity of the vaccine was greater in children younger than 24 months of age (Alonso et al., 2004).
• Side Effects: RTS,S/AS02A and control vaccines were safe and well tolerated. More than 92% of children in both groups received all three doses. Local and general solicited adverse events were of short duration and were mostly mild or moderate in intensity. Grade 3 local or general adverse events were uncommon and of short duration. Local injection-site pain that limited arm motion arose after seven (0.2%) doses in the RTS,S/AS02A group and after one (0.03%) dose in the control vaccine group, and injection-site swelling of more than 20 mm happened after 224 (7.7%) and 14 (0.5%) doses, respectively. General solicited adverse events (fever, irritability, drowsiness, anorexia) that prevented normal activities arose after 55 (1.9%) doses in the RTS,S/AS02A group and 23 (0.8%) doses in the control group. At least one unsolicited adverse event was reported by 653 (64.5%) children in the RTS,S/AS02A group and 597 (59.1%) in the control group. 429 serious adverse events were reported: 180 (17.8%) in the RTS,S/AS02A group and 249 (24.7%) in the control group. 15 children died during the study, five (0.6%) in the RTS,S/AS02A group and ten (1.2%) in the control group. Four of those who died had malaria as a significant contributing factor and all four were in the control group. No serious adverse event or death was judged to be related to vaccination (Alonso et al., 2004).
• Challenge Protocol: Children were not challenged (Alonso et al., 2004)
• Efficacy: Vaccine efficacy for the first clinical episodes was 29.9% (95% CI 11.0-44.8; p=0.004). At the end of the 6-month observation period, prevalence of P falciparum infection was 37% lower in the RTS,S/AS02A group compared with the control group (11.9% vs 18.9%; p=0.0003). Vaccine efficacy for severe malaria was 57.7% (95% CI 16.2-80.6; p=0.019). In cohort 2, vaccine efficacy for extending time to first infection was 45.0% (31.4-55.9; p<0.0001) (Alonso et al., 2004).
• Description: Development of an effective malaria vaccine could greatly contribute to disease control. RTS,S/AS02A is a pre-erythrocytic vaccine candidate based on Plasmodium falciparum circumsporozoite surface antigen. The RTS,S/AS02A vaccine was safe, well tolerated, and immunogenic (Alonso et al., 2004).