Characterisation of natural immune responses to fal vac-l of plasmodium falciparumin children and adults from a holoendemic area of Western Kenya
Previous studies indicate that FAL VAC-1, a recombinant multistage and multicomponent Plasmodium falciparum candidate vaccine containing 12 B cell and 9 T cell epitopes from 9 different antigens of different life cycle stages is immunogenic in animal models and that FAL VAC-1-induced antibodies produced significant antiparasite activities against both sporozoite and blood stages of the parasite. In preparation for vaccine trials in humans, a community based cross-sectional study in a malaria holoendemic area of western Kenya was conducted during April-August 1999, to characterise in vitro natural humoral and cellular immune responses to this candidate vaccine and their association with clinical protection against malaria in young children < 2 years old (N= 180) and their non-pregnant mothers aged 15-48 years (N=139). FAL VAC-1 antigen was used in antibody measurement by ELISA and in lymphoproliferative experiments. Prevalence and level of antibodies were significantly higher in adults than in children when stratified by age groups: 0-6 months; 7-12 months, 13-18 months; 19-24 months; 15-25 years and 26-48 years. Total IgG, IgG1, IgG3 and IgM were the predominant antibodies. IgG2 responses were low and no IgG4 was detected. In children, there were higher IgG 1 levels in parasitaemic group than in the aparasitaemic 'group (F=3.459, p=0.024, t-test). Furthermore, total IgG, IgG1, IgG3 and IgM levels were inversely associated with .' . r '. haemoglobin levels at the time of sampling (total IgG, r=-0.215, p=0.005, IgG1, r=- 0.180, p=0.019; IgG3, r=-0.164, p=0.034; IgM, r=-0.216, p=O.OOl). Parasitaemic children had significantly higher IgG 1 levels at a month prior to sampling. In addition, IgG 1 was positively correlated to the rate of high density parasitaemia and to episodes of clinical malaria (r=0.218, p=0.029 and r=0.237, p=0.018), respectively. However, in adults, aparasitaemic individuals had high total IgG, IgG 1 and IgM levels than parasitaemic individuals (total IgG, F=3.856, p=O.007; IgGl, F=2.701, p=O.007; IgM, F=5.133, p=O.OOl,t-test). In addition, IgG2 was inversely associated with haemoglobin levels at the time of sampling. In contrast to antibody responses, lymphoproliferative responses were higher in children than in adults (one-way ANOV A, F=2.392, p=O.038). Generally, lymphocytes from adults responded at lower antigen concentrations, while those from children responded at higher antigen concentrations. There were no associations between lymphoproliferation and malaria infection or haemoglobin level in either young children or adults. The results of this study therefore indicate that: FAL VAC-l, a multistage multicomponent malaria vaccine candidate is recognised by individuals naturally exposed to malaria. The antibody responses increase whereas lymphoproliferative responses decrease with age. The higher IgG1 levels in children may indicate the presence of a current P. falciparum infection, but in adults from the same holoendemic area, IgG 1, may be associated with protection against parasitaemia.