Immune responses elicited by R21/Matrix-M™ malaria vaccine in children aged 5-36 months: robust one year durability and correlation between long-lived CSP-IgG and vaccine efficacy

Malaria vaccines are a critical addition to global efforts to reduce disease burden, yet our understanding of the durability and immunologic mechanism of action across diverse endemic settings is limited. Here we evaluate humoral immune responses to four components of the R21/Matrix-M™ vaccine following a three-dose primary series and one booster dose administered a year later to children aged 5-36 months across five sites in four malaria-endemic African countries. Here we report robust induction of vaccine-specific antibodies after the primary series and booster dose of R21/Matrix-M™. Younger children aged 5-17 months had higher fold change from pre-vaccination to post-primary series for circumsporozoite protein (CSP)-specific IgG compared with 18-36 month olds (p<0.001) but there was no effect of age on the waning of antibodies in the first year. While baseline parasitemia was associated with higher pre-vaccination anti-CSP IgG titres (p<0.001), pre-vaccination CSP-specific antibodies did not impair the ability of the vaccine to elicit robust antibody responses. Both C-terminal CSP-specific and NANP-repeat IgG titres at 28 and 180 days after the primary series were associated with a reduction in the rate of clinical malaria in the R21/Matrix-MTM study arm. Notably, at one year following primary series, C-terminal CSP-specific IgG titres continued to be associated with a reduction in the rate of clinical malaria (IRR 0.32 (95% CI: 0.17, 0.61), underscoring its potential as a biomarker of vaccine-induced protection.