Characterisation of natural immune responses to fal vac-l of plasmodium falciparumin children and adults from a holoendemic area of Western Kenya
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Date
2000
Authors
Were, Tom
Journal Title
Journal ISSN
Volume Title
Publisher
Kenyatta University
Abstract
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
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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.
Description
Department of Microbiology, 150p. 2000, RA 644.M2W4