Associate Professor
Kwadwo Asamoah Kusi
Project Title
Clinical and immunopathological consequences of chronic HBV and Plasmodium falciparum co-infections
EDCTP Project
TMA2018SF-2456
EDCTP Program
EDCTP2
EDCTP Project Call
Senior Fellowship (SF)
Host Organisation
| Department | Institution | Country |
|---|---|---|
| University of Ghana | Ghana |
Current Organisation
NOGUCHI MEMORIAL INSTITUTE FOR MEDICAL RESEARCH(NM
Current Job Title
Senior Research Fellow
Biography
Publications
Cerebral malaria (CM) may cause death or long-term neurological
damage in children, and several host genetic risk factors
have been reported. Malaria-specific immunoglobulin (Ig) G3
antibodies are crucial to human immune response against malaria.
The hinge region of IgG3 exhibits length polymorphism
(with long [L], medium [M], and short [S] alleles), which may
influence its functionality. We studied IgG3 hinge region length
polymorphisms in 136 Ghanaian children with malaria. Using
logistic regression models, we found that children with the
recessive MM allotype encoding medium IgG3 hinge region
length had an increased risk of CM (adjusted odds ratio, 6.67
[95% confidence interval, 1.30–34.32]; P = .004) . This has implications
for future epidemiological studies on CM.
Sterile protection against clinical malaria has been achieved in animal models and experimental
human challenge studies involving immunization with radiation attenuated Plasmodium falciparum
sporozoite vaccines as well as by live sporozoites under chloroquine prophylaxis. Parasite-specific
IFN-c and granzyme B-secreting CD8 + T cells have been identified as key mediators of protection.
Although the exact parasite targets of protective CD8 + T cell responses are not fully defined,
responses against a handful of vaccine candidate antigens have been associated with protection.
Identifying the T cell targets in these antigens will facilitate the development of simpler, costeffective,
and efficacious next generation multi-epitope vaccines. The aim of this study was to identify
immunodominant portions of four malaria vaccine candidate antigens using peripheral blood
mononuclear cells (PBMCs) from adults with life-long exposure to malaria parasites. Cryopreserved
PBMCs from 291 HLA-typed subjects were stimulated with pools of overlapping 15mer peptides spanning
the entire sequences of P. falciparum circumsporozoite protein (CSP, 9 pools), apical membrane
antigen 1 (AMA1, 12 pools), thrombospondin related anonymous protein (TRAP, 6 pools) and cell
traversal for ookinetes and sporozoites (CelTOS, 4 pools) in FluoroSpot assays. 125 of 291 subjects
made IFN-c responses to 30 of the 31 peptide pools tested and 22 of 291 made granzyme B
responses, with 20 making dual responses. The most frequent responses were to the CSP Cterminal
region and the least frequent responses were to TRAP and CelTOS. There was no association
between FluoroSpot responses and active malaria infection, detected by either microscopy, RDT, or
PCR.
In conclusion, CSP and AMA1 have relatively higher numbers of epitopes that trigger IFN-c and
granzyme B-secreting T cells in adults with life-long malaria parasite exposure compared to the other
two antigens tested, and highlights the continued relevance of these two antigens as vaccine
candidates.