MSc (Med), Faculty of Health Sciences, University of the Witwatersrand, 2009 / Background:
RTS,S candidate malaria vaccine has been shown to be highly immunogenic in children
and infants, but the protective immune mechanisms still remain to be clearly elucidated. It
is believed that RTS,S elicits a strong neutralizing humoral immune response directed
against surface-exposed sporozoite proteins and cell mediated immune (CMI) responses
characterized by predominantly CD4+ Th1 cells. The objective of this study was to
investigate humoral and cell-mediated immune responses to the RTS,S/AS02D malaria
vaccine and its association with protection against infection and disease by P. falciparum.
Methodology and Principal Findings:
This secondary data analysis from data of a phase I/IIb randomized, double-blind,
controlled trial, included 154 healthy infants living in rural Mozambique, previously
immunized with RTS,S/AS02D candidate malaria vaccine or the control Engerix-B™
vaccine.
Antibodies against circumsporozoite protein (CSP) and hepatitis-B surface antigen
(HBsAg) were measured with a standard ELISA. Fresh blood intracellular staining assay
was performed to evaluate the expression of IL-2 and IFN-γ by CD4+ and CD8+ cells in
response to in vitro stimulation of specific peptides. Data was evaluated for association
with the risk of malaria detected by both active and passive case detection of infection over
a period of 6 months post dose 3.
Anti-HBs antibody geometric mean titers declined from 10,082 mIU/mL one month post
Dose 3 to 2,751 mIU/mL at 12 months post Dose 3 in the RTS,S/AS02D group; anti-HBs
v
geometric mean titers were 392.4 mIU/mL and 263.9 mIU/mL, respectively in the Engerix-
BTM group. Anti-CSP antibody geometric mean titers declined from 199.9 EU/mL one
month post Dose 3 to 7.3 EU/mL at 12 months post Dose 3 in the RTS,S/AS02D group.
Median stimulation indices of HBs-specific IL-2 and IFN-γ producing CD8+ T cells was
higher in the RTS,S/AS02D group than in control group (Wilcoxon rank sum p-values for
IFN-γ = 0.015, for IL-2 = 0.030) at 10.5 weeks post immunization. Median stimulation
indices of anti-CSP specific IFN-γ producing CD8+ T cells at the same time point was
1.13 (IQR: 0.79 - 1.67; p=0.029). For specific IL-2-producing CD4+ T cells, the median
SI was 1.14 (IQR: 0.74 – 1.60, p=0.043) at 10.5 weeks post dose three.
The reduction in hazards of malaria infection were 18.3 % (95% CI: -267.9 – 81.8,
p=0.793) and -12.0 % (95% CI: -295 – 68.2, p=0.86) for specific IL-2 CD4+ stimulation
indices; For specific CD8+ IFN-γ stimulation indices the hazards were -103.6% (95%
CI: -690.9 – 47.6; p=0.305) and 48.8% (95% CI: -97.0 – 86.7; p=0.33) at four and 10.5
weeks post immunization respectively.
Conclusion:
The RTS,S/AS02D vaccine was immunogenic and has elicited detectable levels of CSP specific
cell mediated responses. No evidence of association was found between the
antibodies anti-CSP and specific cell mediated responses and the risk of malaria.
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:wits/oai:wiredspace.wits.ac.za:10539/7962 |
| Date | 12 April 2010 |
| Creators | Aide, Pedro Carlos Paulino |
| Source Sets | South African National ETD Portal |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | application/pdf |
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