Antibody levels to multiple malaria vaccine candidate antigens in relation to clinical malaria episodes in children in the Kasena-Nankana district of Northern Ghana

Abstract

BackgroundConsidering the natural history of malaria of continued susceptibility to infection and episodes of illness that decline in frequency and severity over time, studies which attempt to relate immune response to protection must be longitudinal and have clearly specified definitions of immune status. Putative vaccines are expected to protect against infection, mild or severe disease or reduce transmission, but so far it has not been easy to clearly establish what constitutes protective immunity or how this develops naturally, especially among the affected target groups. The present study was done in under six year old children to identify malaria antigens which induce antibodies that correlate with protection from Plasmodium falciparum malaria.MethodsIn this longitudinal study, the multiplex assay was used to measure IgG antibody levels to 10 malaria antigens (GLURP R0, GLURP R2, MSP3 FVO, AMA1 FVO, AMA1 LR32, AMA1 3D7, MSP1 3D7, MSP1 FVO, LSA-1and EBA175RII) in 325 children aged 1 to 6 years in the Kassena Nankana district of northern Ghana. The antigen specific antibody levels were then related to the risk of clinical malaria over the ensuing year using a negative binomial regression model.ResultsIgG levels generally increased with age. The risk of clinical malaria decreased with increasing antibody levels. Except for FMPOII-LSA, (p = 0.05), higher IgG levels were associated with reduced risk of clinical malaria (defined as axillary temperature ≥37.5°C and parasitaemia of ≥5000 parasites/ul blood) in a univariate analysis, upon correcting for the confounding effect of age. However, in a combined multiple regression analysis, only IgG levels to MSP1-3D7 (Incidence rate ratio = 0.84, [95% C.I.= 0.73, 0.97, P = 0.02]) and AMA1 3D7 (IRR = 0.84 [95% C.I.= 0.74, 0.96, P = 0.01]) were associated with a reduced risk of clinical malaria over one year of morbidity surveillance.ConclusionThe data from this study support the view that a multivalent vaccine involving different antigens is most likely to be more effective than a monovalent one. Functional assays, like the parasite growth inhibition assay will be necessary to confirm if these associations reflect functional roles of antibodies to MSP1-3D7 and AMA1-3D7 in this population.

Effect of Seasonal Malaria Chemoprevention (SMC) with SulfadoxinePyrimethamine (SP) and Amodiaquine (AQ) on the Acquisition of antiAMA1 and anti-MSP1_42 Antibodies among Children under 10 Years Living in the Southern part of Senegal (Velingara)

“…Previous study conducted in Senegal showed that antibodies level increases with age, specifically in children over 5 years [29]. These results are in line with those found in Ghana that showed IgG levels increased with age [30].…”

Plasmodium falciparum Malaria in Children Aged 0-2 Years: The Role of Foetal Haemoglobin and Maternal Antibodies to Two Asexual Malaria Vaccine Candidates (MSP3 and GLURP)

“…However other studies did not find a protective effect of antibodies to MSP3 [19], [25], [26] but none of these studies concluded on antibodies to MSP3 appearing as a marker of exposure.…”

“…In Ghana, Dodoo and colleagues reported a protective effect of total IgG and IgG subclasses to GLURP (R0 and R2) in the univariate analysis. However neither total IgG nor IgG subclasses to GLURP (R0 and R2) were significantly protective when all the serological covariates were taken into account in the final multivariable model [19], [25]. In a study conducted in Tanzania by Lusingu and colleagues, total IgG to GLURP R0 was not associated with protection against febrile malaria; among IgG subclasses only IgG1 was associated with protection.…”

Comparative antibody responses against three antimalarial vaccine candidate antigens from urban and rural exposed individuals in Gabon

“…Other studies reported that high levels of anti-MSP1 IgG1 antibodies are associated with protection against malaria attacks [50]. A more recent study from Ghana revealed that the risk of clinical malaria decreased with increasing antibody levels against GLURP R2, MSP3, AMA1, MSP1, and EBA175 [51]. However, the number of children with severe anemia was too low to draw conclusions; further studies are needed to confirm that anti-Pf113 antibodies are associated with protection against anemia.…”