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Kwadwo A Kusi

University Of Ghana, Accra,Legon, Immunology Department, Faculty Member

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Papers by Kwadwo A Kusi

Seroprevalence of Antibodies against Plasmodium falciparum Sporozoite Antigens as Predictive Disease Transmission Markers in an Area of Ghana with Seasonal Malaria Transmission

PLOS ONE, 2016

Cerebral malaria is associated with low levels of circulating endothelial progenitor cells in African children

The American Journal of Tropical Medicine and Hygiene, Apr 1, 2009

Damage to the cerebral microvasculature is a feature of cerebral malaria. Circulating endothelial... more Damage to the cerebral microvasculature is a feature of cerebral malaria. Circulating endothelial progenitor cells are needed for microvascular repair. Based on this knowledge, we hypothesized that the failure to mobilize sufficient circulating endothelial progenitor cells to the cerebral microvasculature is a pathophysiologic feature of cerebral malaria. To test this hypothesis, we compared peripheral blood levels of CD34 + /VEGFR2 + and CD34 + /CD133 + cells and plasma levels of the chemokine stromal cell-derived growth factor 1 (SDF-1) in 214 children in Accra, Ghana. Children with cerebral malaria had lower levels of CD34 + /VEGFR2 + and CD34 + /CD133 + cells compared with those with uncomplicated malaria, asymptomatic parasitemia, or healthy controls. SDF-1 levels were higher in children with acute malaria compared with healthy controls. Together, these results uncover a potentially novel role for endothelial progenitor cell mobilization in the pathophysiology of cerebral malaria.

Immunization with different Pf AMA1 alleles in sequence induces clonal imprint humoral responses that are similar to responses induced by the same alleles as a vaccine cocktail in rabbits

Malar J, 2011

Background: Antibodies to key Plasmodium falciparum surface antigens have been shown to be import... more Background: Antibodies to key Plasmodium falciparum surface antigens have been shown to be important effectors that mediate clinical immunity to malaria. The cross-strain fraction of anti-malarial antibodies may however be required to achieve strain-transcending immunity. Such antibody responses against Plasmodium falciparum apical membrane antigen 1 (PfAMA1), a vaccine target molecule that is expressed in both liver and blood stages of the parasite, can be elicited through immunization with a mixture of allelic variants of the parasite molecule. Cross-strain antibodies are most likely elicited against epitopes that are shared by the allelic antigens in the vaccine cocktail. Methods: A standard competition ELISA was used to address whether the antibody response can be further focused on shared epitopes by exclusively boosting these common determinants through immunization of rabbits with different PfAMA1 alleles in sequence. The in vitro parasite growth inhibition assay was used to further evaluate the functional effects of the broadened antibody response that is characteristic of multi-allele vaccine strategies. Results: A mixed antigen immunization protocol elicited humoral responses that were functionally similar to those elicited by a sequential immunization protocol (p > 0.05). Sequential exposure to the different PfAMA1 allelic variants induced immunological recall of responses to previous alleles and yielded functional cross-strain antibodies that would be capable of optimal growth inhibition of variant parasites at high enough concentrations. Conclusions: These findings may have implications for the current understanding of the natural acquisition of clinical immunity to malaria as well as for rational vaccine design.

A STAT6 Intronic Single-Nucleotide Polymorphism is Associated with Clinical Malaria in Ghanaian Children

Genetics & Epigenetics, 2016

Malaria pathogenesis may be influenced by IgE responses and cytokine cross-regulation. Several mu... more Malaria pathogenesis may be influenced by IgE responses and cytokine cross-regulation. Several mutations in the IL-4/STAT6 signaling pathway can alter cytokine cross-regulation and IgE responses during a Plasmodium falciparum malarial infection. This study investigated the relationship between a STAT6 intronic single-nucleotide polymorphism (rs3024974), total IgE, cytokines, and malaria severity in 238 Ghanaian children aged between 0.5 and 13 years. Total IgE and cytokine levels were measured by ELISA, while genotyping was done by polymerase chain reaction-restriction fragment length polymorphism (RFLP). Compared with healthy controls, heterozygosity protected against clinical malaria: uncomplicated malaria (odds ratios [OR] = 0.13, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001), severe malarial anemia (OR = 0.18, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001), and cerebral malaria (OR = 0.39, P = 0.022). Levels of total IgE significantly differed among malaria phenotypes (P = 0.044) and rs3024974 genotypes (P = 0.037). Neither cytokine levels nor IL-6/IL-10 ratios were associated with malaria phenotypes or rs3024974 genotypes. This study suggests a role for rs3024974 in malaria pathogenesis and offers further insights into an IL-4/STAT6 pathway mutation in malaria pathogenesis.

Measurement of ex vivo ELISpot interferon-gamma recall responses to Plasmodium falciparum AMA1 and CSP in Ghanaian adults with natural exposure to malaria

Malaria Journal, 2016

Malaria eradication requires a concerted approach involving all available control tools, and an e... more Malaria eradication requires a concerted approach involving all available control tools, and an effective vaccine would complement these efforts. An effective malaria vaccine should be able to induce protective immune responses in a genetically diverse population. Identification of immunodominant T cell epitopes will assist in determining if candidate vaccines will be immunogenic in malaria-endemic areas. This study therefore investigated whether class I-restricted T cell epitopes of two leading malaria vaccine antigens, Plasmodium falciparum circumsporozoite protein (CSP) and apical membrane antigen-1 (AMA1), could recall T cell interferon-γ responses from naturally exposed subjects using ex vivo ELISpot assays. Thirty-five subjects aged between 24 and 43 years were recruited from a malaria-endemic urban community of Ghana in 2011, and their peripheral blood mononuclear cells (PBMCs) were tested in ELISpot IFN-γ assays against overlapping 15mer peptide pools spanning the entire CSP and AMA1 antigens, and 9-10mer peptide epitope mixtures that included previously identified and/or predicted human leukocyte antigen (HLA) class 1-restricted epitopes from same two antigens. For CSP, 26 % of subjects responded to at least one of the nine 15mer peptide pools whilst 17 % responded to at least one of the five 9-10mer HLA-restricted epitope mixtures. For AMA1, 63 % of subjects responded to at least one of the 12 AMA1 15mer peptide pools and 51 % responded to at least one of the six 9-10mer HLA-restricted epitope mixtures. Following analysis of data from the two sets of peptide pools, along with bioinformatics predictions of class I-restricted epitopes and the HLA supertypes expressed by a subset of study subjects, peptide pools that may contain epitopes recognized by multiple HLA supertypes were identified. Collectively, these results suggest that natural transmission elicits ELISpot IFN-γ activities to class 1-restricted epitopes that are largely HLA-promiscuous. These results generally demonstrate that CSP and AMA1 peptides recalled ELISpot IFN-γ responses from naturally exposed individuals and that both CSP and AMA1 contain diverse class 1-restricted epitopes that are HLA-promiscuous and are widely recognized in this population.

Towards a blood stage malaria vaccine, dealing with allelic polymorphism in the vaccine candidate apical membrane antigen 1

Effects of ABO Blood Groups on the Clinical Outcome of Malaria in Ghanaian Pregnant Women

Pregnancy-associated malaria is a severe form of malaria for which over 50 million pregnant women... more Pregnancy-associated malaria is a severe form of malaria for which over 50 million pregnant women are at risk. In sub-Saharan Africa, pregnancy-associated malaria is most common in primigravid women and is caused mainly by Plasmodium falciparum variants that have the ability to sequester in placental tissues. This can result in maternal anaemia, intrauterine growth retardation, low birth weight and may even lead to maternal and foetal death. Red blood cells from different blood groups (A, B, AB, and O) may differentially support parasite growth and sequestration. Antibodies and cytokines are believed to be important mediators in pregnancy-associated malaria but little information is available on the influence of the ABO blood groups on the production of P. falciparum-specific antibodies and cytokines. This study was conducted to determine the association of ABO blood groups with the plasma levels of IgG, IgM and the cytokines TNF-α and IL10 in eighty pregnant women at various stages...

Cerebral malaria is associated with low levels of circulating endothelial progenitor cells in African children

The American journal of tropical medicine and hygiene, 2009

Damage to the cerebral microvasculature is a feature of cerebral malaria. Circulating endothelial... more Damage to the cerebral microvasculature is a feature of cerebral malaria. Circulating endothelial progenitor cells are needed for microvascular repair. Based on this knowledge, we hypothesized that the failure to mobilize sufficient circulating endothelial progenitor cells to the cerebral microvasculature is a pathophysiologic feature of cerebral malaria. To test this hypothesis, we compared peripheral blood levels of CD34 (+)/VEGFR2(+) and CD34 (+)/CD133(+) cells and plasma levels of the chemokine stromal cell-derived growth factor 1 (SDF-1) in 214 children in Accra, Ghana. Children with cerebral malaria had lower levels of CD34 (+)/VEGFR2(+) and CD34 (+)/CD133(+) cells compared with those with uncomplicated malaria, asymptomatic parasitemia, or healthy controls. SDF-1 levels were higher in children with acute malaria compared with healthy controls. Together, these results uncover a potentially novel role for endothelial progenitor cell mobilization in the pathophysiology of cerebr...

Cohort study of the association of antibody levels to AMA 1, MSP 119, MSP 3 and GLURP with protection from clinical malaria in Ghanaian children

by Samuel Bosomprah and Kwadwo A Kusi

Malaria …, 2008

Background: Antigen-specific antibody-mediated immune responses play an important role in natural... more Background: Antigen-specific antibody-mediated immune responses play an important role in natural protection against clinical malaria, but conflicting estimates of this association have emerged from immuno-epidemiological studies in different geographical settings. This study was aimed at assessing in a standardized manner the relationship between the antibody responses to four malaria vaccine candidate antigens and protection from clinical malaria, in a cohort of Ghanaian children.

Generation of Humoral Immune Responses to Multi-Allele PfAMA1 Vaccines; Effect of Adjuvant and Number of Component Alleles on the Breadth of Response

PLoS ONE, 2010

There is increasing interest in multi-allele vaccines to overcome strain-specificity against poly... more There is increasing interest in multi-allele vaccines to overcome strain-specificity against polymorphic vaccine targets such as Apical Membrane Antigen 1 (AMA1). These have been shown to induce broad inhibitory antibodies in vitro and formed the basis for the design of three Diversity-Covering (DiCo) proteins with similar immunological effects. The antibodies produced are to epitopes that are shared between vaccine alleles and theoretically, increasing the number of component AMA1 alleles is expected to broaden the antibody response. A plateau effect could however impose a limit on the number of alleles needed to achieve the broadest specificity. Moreover, production cost and the vaccine formulation process would limit the number of component alleles. In this paper, we compare rabbit antibody responses elicited with multi-allele vaccines incorporating seven (three DiCos and four natural AMA1 alleles) and three (DiCo mix) antigens for gains in broadened specificity. We also investigate the effect of three adjuvant platforms on antigen specificity and antibody functionality. Our data confirms a broadened response after immunisation with DiCo mix in all three adjuvants. Higher antibody titres were elicited with either CoVaccine HT TM or Montanide ISA 51, resulting in similar in vitro inhibition (65-82%) of five out of six culture-adapted P. falciparum strains. The antigen binding specificities of elicited antibodies were also similar and independent of the adjuvant used or the number of vaccine component alleles. Thus neither the four extra antigens nor adjuvant had any observable benefits with respect to specificity broadening, although adjuvant choice influenced the absolute antibody levels and thus the extent of parasite inhibition. Our data confirms the feasibility and potential of multi-allele PfAMA1 formulations, and highlights the need for adjuvants with improved antibody potentiation properties for AMA1-based vaccines.

Humoral Immune Response to Mixed PfAMA1 Alleles; Multivalent PfAMA1 Vaccines Induce Broad Specificity

PLoS ONE, 2009

Apical Membrane Antigen 1 (AMA1), a merozoite protein essential for red cell invasion, is a candi... more Apical Membrane Antigen 1 (AMA1), a merozoite protein essential for red cell invasion, is a candidate malaria vaccine component. Immune responses to AMA1 can protect in experimental animal models and antibodies isolated from AMA1vaccinated or malaria-exposed humans can inhibit parasite multiplication in vitro. The parasite is haploid in the vertebrate host and the genome contains a single copy of AMA1, yet on a population basis a number of AMA1 molecular surface residues are polymorphic, a property thought to be primarily as a result of selective immune pressure. After immunisation with AMA1, antibodies more effectively inhibit strains carrying homologous AMA1 genes, suggesting that polymorphism may compromise vaccine efficacy. Here, we analyse induction of broad strain inhibitory antibodies with a multi-allele Plasmodium falciparum AMA1 (PfAMA1) vaccine, and determine the relative importance of cross-reactive and strain-specific IgG fractions by competition ELISA and in vitro parasite growth inhibition assays. Immunisation of rabbits with a PfAMA1 allele mixture yielded an increased proportion of antibodies to epitopes common to all vaccine alleles, compared to single allele immunisation. Competition ELISA with the anti-PfAMA1 antibody fraction that is cross-reactive between FVO and 3D7 AMA1 alleles showed that over 80% of these common antibodies were shared with other PfAMA1 alleles. Furthermore, growth inhibition assays revealed that for any PfAMA1 allele (FVO or 3D7), the cross-reactive fraction alone, on basis of weight, had the same functional capacity on homologous parasites as the total affinity-purified IgGs (cross-reactive+strainspecific). By contrast, the strain-specific IgG fraction of either PfAMA1 allele showed slightly less inhibition of red cell invasion by homologous strains. Thus multi-allele immunisation relatively increases the levels of antibodies to common allele epitopes. This explains the broadened cross inhibition of diverse malaria parasites, and suggests multi-allele approaches warrant further clinical investigation.

The Quantity and Quality of African Children's IgG Responses to Merozoite Surface Antigens Reflect Protection against Plasmodium falciparum Malaria

PLoS ONE, 2009

Background: Antibodies, particularly cytophilic IgG subclasses, with specificity for asexual bloo... more Background: Antibodies, particularly cytophilic IgG subclasses, with specificity for asexual blood stage antigens of Plasmodium falciparum, are thought to play an important role in acquired immunity to malaria. Evaluating such responses in longitudinal sero-epidemiological field studies, allied to increasing knowledge of the immunological mechanisms associated with anti-malarial protection, will help in the development of malaria vaccines.

format_quoteThe study validated associations between antibody responses and protection from malaria attacks, confirming statistical power.format_quote

Immunization with different PfAMA1 alleles in sequence induces clonal imprint humoral responses that are similar to responses induced by the same alleles as a vaccine cocktail in rabbits

Malaria Journal, 2011

Background: Antibodies to key Plasmodium falciparum surface antigens have been shown to be import... more Background: Antibodies to key Plasmodium falciparum surface antigens have been shown to be important effectors that mediate clinical immunity to malaria. The cross-strain fraction of anti-malarial antibodies may however be required to achieve strain-transcending immunity. Such antibody responses against Plasmodium falciparum apical membrane antigen 1 (PfAMA1), a vaccine target molecule that is expressed in both liver and blood stages of the parasite, can be elicited through immunization with a mixture of allelic variants of the parasite molecule. Cross-strain antibodies are most likely elicited against epitopes that are shared by the allelic antigens in the vaccine cocktail. Methods: A standard competition ELISA was used to address whether the antibody response can be further focused on shared epitopes by exclusively boosting these common determinants through immunization of rabbits with different PfAMA1 alleles in sequence. The in vitro parasite growth inhibition assay was used to further evaluate the functional effects of the broadened antibody response that is characteristic of multi-allele vaccine strategies. Results: A mixed antigen immunization protocol elicited humoral responses that were functionally similar to those elicited by a sequential immunization protocol (p > 0.05). Sequential exposure to the different PfAMA1 allelic variants induced immunological recall of responses to previous alleles and yielded functional cross-strain antibodies that would be capable of optimal growth inhibition of variant parasites at high enough concentrations. Conclusions: These findings may have implications for the current understanding of the natural acquisition of clinical immunity to malaria as well as for rational vaccine design.

Anti-sporozoite antibodies as alternative markers for malaria transmission intensity estimation

by Samuel Bosomprah, Emmanuel Dickson, and Kwadwo A Kusi

Malaria Journal, 2014

Background: Reported malaria cases continue to decline globally, and this has been attributed to ... more Background: Reported malaria cases continue to decline globally, and this has been attributed to strategic implementation of multiple malaria control tools. Gains made would however need to be sustained through continuous monitoring to ensure malaria elimination and eradication. Entomological inoculation rate (EIR) is currently the standard tool for transmission monitoring but this is not sensitive enough, especially in areas of very low transmission. Transmission estimation models based on seroconversion rates (λ) of antibodies to Plasmodium falciparum blood stage antigens are gaining relevance. Estimates of λ, which is the measure of transmission intensity, correlate with EIR but are limited by long-term persistence of antibodies to blood stage antigens. Seroprevalence of antibodies to sporozoite antigens may be better alternatives since these antigens usually have shorter immune exposure times. The aim of this study was to develop transmission estimation models based on the seroprevalence of antibodies to two P. falciparum sporozoite antigens (CSP, CelTOS) and compare with models based on the classical blood stage antigen AMA1.

Safety and immunogenicity of multi-antigen AMA1-based vaccines formulated with CoVaccine HT™ and Montanide ISA 51 in rhesus macaques

Malaria Journal, 2011

Background: Increasing the breadth of the functional antibody response through immunization with ... more Background: Increasing the breadth of the functional antibody response through immunization with Plasmodium falciparum apical membrane antigen 1 (PfAMA1) multi-allele vaccine formulations has been demonstrated in several rodent and rabbit studies. This study assesses the safety and immunogenicity of three PfAMA1 Diversity-Covering (DiCo) vaccine candidates formulated as an equimolar mixture (DiCo mix) in CoVaccine HT™ or Montanide ISA 51, as well as that of a PfAMA1-MSP1 19 fusion protein formulated in Montanide ISA 51. Methods: Vaccine safety in rhesus macaques was monitored by animal behaviour observation and assessment of organ and systemic functions through clinical chemistry and haematology measurements. The immunogenicity of vaccine formulations was assessed by enzyme-linked immunosorbent assays and in vitro parasite growth inhibition assays with three culture-adapted P. falciparum strains. Results: These data show that both adjuvants were well tolerated with only transient changes in a few of the chemical and haematological parameters measured. DiCo mix formulated in CoVaccine HT™ proved immunologically and functionally superior to the same candidate formulated in Montanide ISA 51. Immunological data from the fusion protein candidate was however difficult to interpret as four out of six immunized animals were non-responsive for unknown reasons. Conclusions: The study highlights the safety and immunological benefits of DiCo mix as a potential human vaccine against blood stage malaria, especially when formulated in CoVaccine HT™, and adds to the accumulating data on the specificity broadening effects of DiCo mix.

P171 Severity of Plasmodium falciparum infection in Ghanaian children is associated with a STAT6 single nucleotide polymorphism

International Journal of Antimicrobial Agents, 2009

The objective of this study was to elucidate the precise mechanisms by which E. coli K1 makes DCs... more The objective of this study was to elucidate the precise mechanisms by which E. coli K1 makes DCs tolerogenic. Methods: DCs were isolated from healthy volunteers and infected with E. coli K1 in vitro for varying times. Expression of costimulatory markers as well CD47 on DCs was assessed by flow cytometry. Thromospondin-1 (TSP-1) levels were estimated in DC-E. coli coculture supernatants by ELISA. Antigen presentation was evaluated by co-culturing DCs and T cells in mixed lymphocyte reaction (MLR). Results: Here, our studies demonstrated that the interaction of OmpA + E. coli K1 with DCs enhances the expression of CD47, an integrin associated molecule reported to induce tolerogenicity in immune cells like T cells. In addition, a significant increase in the expression of TSP-1, a natural ligand for CD47, on the surface of DCs and in the supernatants was observed. In contrast, OmpA E. coli, which promotes the maturation of DCs, failed to upregulate the expression of CD47 and TSP-1 in DCs. Pretreatment of DCs with CD47 blocking antibodies led to maturation of DCs substantiating the role of CD47 in OmpA + E. coli K1 mediated tolerogenicity. Furthermore, OmpA + E. coli K1 infected DCs failed to present antigen to T cells. Conclusions: The present study identified an important and novel mechanism by which E. coli K1 makes DCs tolerogenic by upregulating the expression of CD47. Targeting CD47 might help in restoring maturation of DCs in response to E. coli K1 leading to efficient antigen presentation thus promoting clearance of bacteria.

Levels of Soluble CD163 and Severity of Malaria in Children in Ghana

by Kwadwo A Kusi, Daniel Dodoo, George Obeng-adjei, and Kwadwo Kusi

Clinical and Vaccine Immunology, 2008

CD163 is an acute-phase-regulated monocyte/macrophage membrane receptor expressed late in inflamm... more CD163 is an acute-phase-regulated monocyte/macrophage membrane receptor expressed late in inflammation. It is involved in the haptoglobin-mediated removal of free hemoglobin from plasma, has been identified as a naturally soluble plasma glycoprotein with potential anti-inflammatory properties, and is possibly linked to an individual's haptoglobin phenotype. High levels of soluble CD163 (sCD163) in a malaria episode may therefore downregulate inflammation and curb disease severity. In order to verify this, the relationships between sCD163 levels, malaria severity, and selected inflammatory mediators tumor necrosis factor alpha [TNF-␣], interleukin-6 [IL-6], and IL-10) were assessed by enzyme-linked immunosorbent assay using plasma samples obtained from pediatric malaria patients with uncomplicated malaria (UM [n ‫؍‬ 38]), cerebral malaria (CM [n ‫؍‬ 52]), and severe malarial anemia (SA [n ‫؍‬ 55]) during two consecutive malaria transmission seasons (2002 and 2003)

format_quoteMedian sCD163 levels were highest in UM patients (11.9 g/ml), significantly differing from CM (8.0 g/ml) and SA patients (7.7 g/ml).format_quote

Measurement of the plasma levels of antibodies against the polymorphic vaccine candidate apical membrane antigen 1 in a malaria-exposed population

by Kwadwo A Kusi and Samuel Bosomprah

BMC Infectious Diseases, 2012

Background: Establishing antibody correlates of protection against malaria in human field studies... more Background: Establishing antibody correlates of protection against malaria in human field studies and clinical trials requires, amongst others, an accurate estimation of antibody levels. For polymorphic antigens such as apical membrane antigen 1 (AMA1), this may be confounded by the occurrence of a large number of allelic variants in nature. Methods: To test this hypothesis, plasma antibody levels in an age-stratified cohort of naturally exposed children from a malaria-endemic area in Southern Ghana were determined by indirect ELISA. Titres against four single PfAMA1 alleles were compared with those against three different allele mixtures presumed to have a wider repertoire of epitope specificities. Associations of antibody levels with the incidence of clinical malaria as well as with previous exposure to parasites were also examined. Results: Antibody titres against PfAMA1 alleles generally increased with age/exposure while antibody specificity for PfAMA1 variants decreased, implying that younger children (≤ 5 years) elicit a more strain-specific antibody response compared to older children. Antibody titre measurements against the FVO and 3D7 AMA1 alleles gave the best titre estimates as these varied least in pair-wise comparisons with titres against all PfAMA1 allele mixtures. There was no association between antibody levels against any capture antigen and either clinical malaria incidence or parasite density.

format_quoteNo association found between antibody levels and clinical malaria incidence or parasite density, highlighting the role of antigenic variability in antibody response.format_quote

Measuring naturally acquired ex vivo IFN-γ responses to Plasmodium falciparum cell-traversal protein for ookinetes and sporozoites (CelTOS) in Ghanaian adults

by Kwadwo A Kusi, Martha Sedegah, and Edem Badji

Background: A malaria vaccine that targets the sporozoite/liver stage parasites could potentially... more Background: A malaria vaccine that targets the sporozoite/liver stage parasites could potentially prevent blood
stage infection and the associated clinical symptoms. Identification of sporozoite/liver stage antigens is, therefore,
crucial for the development of effective vaccines. Cell-traversal protein for ookinetes and sporozoites (CelTOS) is a
highly conserved antigen involved in sporozoite motility and hepatocyte invasion and has been shown to induce
significant IFN-γ production in PBMCs from radiation-attenuated sporozoite-immunized malaria-naïve individuals.
The aim of this study was to ascertain whether such CelTOS-specific recall responses are also induced in individuals
with natural exposure to Plasmodium falciparum.
Methods: Ex vivo IFN-γ responses to 15mer overlapping peptide pools covering the entire sequence of CelTOS and
five other candidate antigens, CSP, AMA1, MSP1, TRAP and LSA1, were characterized using PBMCs from 35 malaria
exposed adults. Responses to four CelTOS peptide pools (CelTp1, CelTp2, CelTp3 and CelTp4), a pool containing
peptides from the entire CelTOS antigen (CelTTp), and pools comprised of overlapping peptides from each of the
other five malaria antigens were assessed by ex vivo ELISpot assay. A positive IFN-γ response for stimulants was
defined by two criteria; a stimulation index of two or greater relative to the unstimulated control, and a difference
of 10 or greater in spot forming cells between stimulant and the unstimulated control.
Results: Of the 35 volunteers tested, five had positive IFN-γ recall responses against the four different CelTOS pools
while four volunteers made responses against the CelTTp pool; six volunteers were, therefore, positive with CelTOS.
By contrast, six volunteers responded to AMA1, seven to LSA1, 15 to MSP1 and two volunteers responded against
CSP and TRAP.
Conclusions: These results suggest natural malaria transmission induces CelTOS-specific ex vivo IFN-γ in Ghanaian
adults and that the frequency of these responses was similar to those of other previously characterized malaria
antigens. These findings support the further evaluation of CelTOS as a pre-erythrocytic candidate antigen for inclusion
in a potential multi-antigen vaccine.

format_quote14% of participants responded positively to CelTOS peptide pools, demonstrating potential immunogenicity within endemic populations.format_quote

High Plasma Levels of Soluble Intercellular Adhesion Molecule (ICAM)-1 Are Associated with Cerebral Malaria

by Selorme Adukpo, Michael Fokuo Ofori, and Kwadwo A Kusi

PLoS ONE, 2013

Background: Cerebral malaria (CM) is responsible for most of the malaria-related deaths in childr... more Background: Cerebral malaria (CM) is responsible for most of the malaria-related deaths in children in sub-Saharan Africa. Although, not well understood, the pathogenesis of CM involves parasite and host factors which contribute to parasite sequestration through cytoadherence to the vascular endothelium. Cytoadherence to brain microvasculature is believed to involve host endothelial receptor, CD54 or intercellular adhesion molecule (ICAM)-1, while other receptors such as CD36 are generally involved in cytoadherence of parasites in other organs. We therefore investigated the contributions of host ICAM-1 expression and levels of antibodies against ICAM-1 binding variant surface antigen (VSA) on parasites to the development of CM.