Multifunctional antibodies are induced by the RTS, S malaria vaccine and associated with protection in a phase 1/2a trial
The Journal of infectious diseases, 2021•academic.oup.com
Background RTS, S is the leading malaria vaccine candidate but only confers partial efficacy
against malaria in children. RTS, S is based on the major Plasmodium falciparum sporozoite
surface antigen, circumsporozoite protein (CSP). The induction of anti-CSP antibodies is
important for protection; however, it is unclear how these protective antibodies function.
Methods We quantified the induction of functional anti-CSP antibody responses in healthy
malaria-naive adults (N= 45) vaccinated with RTS, S/AS01. This included the ability to …
against malaria in children. RTS, S is based on the major Plasmodium falciparum sporozoite
surface antigen, circumsporozoite protein (CSP). The induction of anti-CSP antibodies is
important for protection; however, it is unclear how these protective antibodies function.
Methods We quantified the induction of functional anti-CSP antibody responses in healthy
malaria-naive adults (N= 45) vaccinated with RTS, S/AS01. This included the ability to …
Background
RTS,S is the leading malaria vaccine candidate but only confers partial efficacy against malaria in children. RTS,S is based on the major Plasmodium falciparum sporozoite surface antigen, circumsporozoite protein (CSP). The induction of anti-CSP antibodies is important for protection; however, it is unclear how these protective antibodies function.
Methods
We quantified the induction of functional anti-CSP antibody responses in healthy malaria-naive adults (N = 45) vaccinated with RTS,S/AS01. This included the ability to mediate effector functions via the fragment crystallizable (Fc) region, such as interacting with human complement proteins and Fcγ-receptors (FcγRs) that are expressed on immune cells, which promote various immunological functions.
Results
Our major findings were (1) RTS,S-induced antibodies mediated Fc-dependent effector functions, (2) functional antibodies were generally highest after the second vaccine dose, (3) functional antibodies targeted multiple regions of CSP, (4) participants with higher levels of functional antibodies had a reduced probability of developing parasitemia following homologous challenge (P < .05), and (5) nonprotected subjects had higher levels of anti-CSP IgM.
Conclusions
Our data suggest a role for Fc-dependent antibody effector functions in RTS,S-induced immunity. Enhancing the induction of these functional activities may be a strategy to improve the protective efficacy of RTS,S or other malaria vaccines.
Clinical Trials Registration
NCT00075049
Oxford University Press