Vaccine 29 (2011) 6059–6067 Contents lists available at ScienceDirect Vaccine jou rn al h om epa ge: www.elsevier.com/locate/vaccine Four year immunogenicity of the RTS,S/AS02 A malaria vaccine in Mozambican children during a phase IIb trial Pedro Aide a,b,∗ , Carlota Doba ˜ no a,c , Jahit Sacarlal a,d , John J. Aponte a,c , Inácio Mandomando a,b , Caterina Guinovart a,c , Quique Bassat a,c , Montse Renom a,c , Laura Puyol c , Eusebio Macete a,b , Esperanza Herreros g , Amanda Leach e , Marie-Claude Dubois e , Marie-Ange Demoitie e , Marc Lievens e , Johan Vekemans e , Christian Loucq f , W. Ripley Ballou e , Joe Cohen e , Pedro L. Alonso a,c a Centro de Investigac ¸ ão em Saúde de Manhic ¸ a (CISM), Manhic ¸ a, Mozambique b Instituto Nacional de Saúde, Ministério de Saúde, Maputo, Mozambique c Barcelona Centre for International Health Research/Hospital Clinic/University of Barcelona, Spain d Faculdade de Medicina, Universidade Eduardo Mondlane, Maputo, Mozambique e GlaxoSmithKline Biologicals, Rixensart, Belgium f PATH Malaria Vaccine Initiative, Bethesda, MD, USA g GlaxoSmithKline, Tres Cantos, Madrid, Spain a r t i c l e i n f o Article history: Received 25 September 2010 Received in revised form 9 March 2011 Accepted 12 March 2011 Available online 7 April 2011 Keywords: RTS S/AS02 A Malaria Vaccine Immunogenicity Children a b s t r a c t Previous studies with the malaria vaccine RTS,S/AS02 A in young children in a malaria endemic area of Mozambique have shown it to have a promising safety profile and to reduce the risk of Plasmodium falciparum infection and disease. In this study, we assessed the antibody responses to the P. falciparum and hepatitis B components of the RTS,S/AS02 A vaccine over a 45 months surveillance period in a large phase IIb trial which included 2022 children aged 1–4 years at recruitment. The RTS,S/AS02 A vaccine induced high anti-circumsporozoite antibody levels with at least 96% of chil- dren remaining seropositive during the entire follow-up period. IgG titers decayed over the first 6 months of follow-up to about 25% of the initial level, but still remained 30-fold higher until month 45 compared to controls. Children with higher levels of naturally acquired immunity at baseline, assessed by blood stage indirect fluorescent antibody test, had slightly higher anti-circumsporozoite levels, after adjusting for the effect of age. The RTS,S/AS02 A vaccine also induced high levels of anti-hepatitis B surface antigen antibodies (sero- protection >97%). RTS,S/AS02 A vaccine is immunogenic and induces long-lasting anti-circumsporozoite antibodies, per- sisting at least 42 months after immunization. These antibodies may play a role in protection against malaria. © 2011 Elsevier Ltd. All rights reserved. 1. Introduction Plasmodium falciparum is responsible for the high malaria mor- bidity and mortality in malaria endemic countries, accounting for around 250 million clinical malaria cases and 863,000 deaths every year [1]. The GlaxoSmithKline (GSK) Biologicals pre-erythrocytic RTS,S malaria vaccine antigen is a virus-like particle contain- ing a mixture of RTS, a chimeric recombinant protein combining ∗ Corresponding author at: Centro de Investigac ¸ ão em Saúde da Manhic ¸ a (CISM), Instituto Nacional de Saúde, Ministério de Saúde, Rua 12, P.O. Box 1929, Maputo, Mozambique. Tel.: +258 21 810181; fax: +258 21 810002. E-mail addresses: pedro.aide@manhica.net, pcpaid@gmail.com (P. Aide). polypeptide regions of P. falciparum circumsporozoite protein (CSP) and the hepatitis B virus surface antigen (HBsAg), and S, the recom- binant HBsAg alone. It is formulated in the AS02 adjuvant system [2,3]. Developments of this vaccine has included sequential steps of phase I and phase IIa studies in adults in the USA [3], phase I/IIb studies in adults in The Gambia [4], and finally children and infant studies in Mozambique [5–7] and Tanzania [8]. We have shown that the vaccine is immunogenic, inducing immunoglob- ulin G (IgG) humoral antibodies and CD4 + T cell and cytokine responses to P. falciparum CSP [9]. Some previous trials have shown an association between anti-CSP IgG levels in serum (measured by a standardized ELISA) and vaccine efficacy against malaria infection, but not against clinical disease [7,10,11]. The protective immune mechanism of RTS,S/AS remains poorly understood, and 0264-410X/$ – see front matter © 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.vaccine.2011.03.041