Malaria has an enormous public health impact and new preventive interventions are urgently needed. After more than 100 years of research on malaria vaccines, RTS,S was the first pre-erythrocytic vaccine candidate that entered phase III clinical development [
1-
3]. RTS,S contains hepatitis B surface antigen (HBsAg) together with a fusion protein of HBsAg and a carboxy-terminal fragment of
Plasmodium falciparum circumsporozoite protein (CSP), co-expressed in yeast and formulated with a proprietary adjuvant (AS01). The exact mechanism of RTS,S-mediated protection is not known, although Immunoglobulin G antibodies (IgG) against the CSP repeat region are likely to play an important role since the concentration of anti-CSP IgG partly explains protection in most studies that assessed efficacy of RTS,S in African children [
4-
6]. In addition, passive transfer of anti-CSP IgG can protect animals from subsequent challenge [
7,
8]. Besides concentration, many other properties determine antibody function. Among them are availability of effector molecules, post-translational modification, isotype, subclass, affinity and avidity of antibodies. It is difficult to measure all these characteristics in one sample, particularly in the small sample volumes obtained during clinical trials in infants. Affinity, defined as the strength of interaction between an epitope and an antibody binding site, would be a particularly interesting variable to measure in the context of anti-CSP IgG-mediated immunity, since the time of interaction with the parasite is short (less than 30 minutes [
9]), sporozoites are strongly diluted and few. In fact, only one successful hepatocyte infection is sufficient to initiate and maintain blood stage infection. Studies in mice have shown that high antibody affinity against a synthetic CSP immunogen is positively associated with protection [
8,
10] and most studies in humans indicate that anti-CSP IgG concentration explains only parts of the vaccine-mediated protection. Increase in antibody affinity after repeated antigen exposure is the result of affinity maturation due to somatic hypermutation. The rate and extent of maturation may be influenced by several factors, including nature, route and dose of the antigen, adjuvants and carriers as well as the immunization schedule. In the present study antibody avidity was measured. It is a representation of the strength of interaction between antibodies and antigens in a complex and besides antibody affinity, valences of antibodies and antigens as well as structural features of the complex are important determinants of avidity. For CSP, it has been shown that the use of some adjuvants can increase the avidity of anti-CSP IgG after vaccination of human volunteers [
11]. In this study IgG avidity against the repeat region of CSP was measured after the second and third injection of RTS,S/AS01
E in infants that received the vaccine as part of a phase IIb clinical trial to assess safety and efficacy of RTS,S/AS01
E in the age-group targeted by the expanded programme on immunization (EPI) [
5,
12].