Imperial College London

DrJuliaMakinde

Faculty of MedicineDepartment of Infectious Disease

Research Associate
 
 
 
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j.makinde

 
 
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Chelsea and Westminster HospitalChelsea and Westminster Campus

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Summary

 

Publications

Publication Type
Year
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34 results found

Makinde J, Nduati EW, Freni-Sterrantino A, Streatfield C, Kibirige C, Dalel J, Black SL, Hayes P, Macharia G, Hare J, McGowan E, Abel B, King D, Joseph S, Hunter E, Sanders EJ, Price M, Gilmour Jet al., 2021, A novel sample selection approach to aid the identification of factors that correlate wth the control of HIV-1 infection, Frontiers in Immunology, Vol: 12, Pages: 1-12, ISSN: 1664-3224

Individuals infected with HIV display varying rates of viral control and disease progression, with a small percentage of individuals being able to spontaneously control infection in the absence of treatment. In attempting to define the correlates associated with natural protection against HIV, extreme heterogeneity in the datasets generated from systems methodologies can be further complicated by the inherent variability encountered at the population, individual, cellular and molecular levels. Furthermore, such studies have been limited by the paucity of well-characterised samples and linked epidemiological data, including duration of infection and clinical outcomes. To address this, we selected 10 volunteers who rapidly and persistently controlled HIV, and 10 volunteers each, from two control groups who failed to control (based on set point viral loads) from an acute and early HIV prospective cohort from East and Southern Africa. A propensity score matching approach was applied to control for the influence of five factors (age, risk group, virus subtype, gender, and country) known to influence disease progression on causal observations. Fifty-two plasma proteins were assessed at two timepoints in the 1st year of infection. We independently confirmed factors known to influence disease progression such as the B*57 HLA Class I allele, and infecting virus Subtype. We demonstrated associations between circulating levels of MIP-1α and IL-17C, and the ability to control infection. IL-17C has not been described previously within the context of HIV control, making it an interesting target for future studies to understand HIV infection and transmission. An in-depth systems analysis is now underway to fully characterise host, viral and immunological factors contributing to control.

Journal article

Boelen L, Debebe B, Silveira M, Salam A, Makinde J, Roberts CH, Wang ECY, Frater J, Gilmour J, Twigger K, Ladell K, Miners KL, Jayaraman J, Traherne JA, Price DA, Qi Y, Martin MP, Macallan DC, Thio CL, Astemborski J, Kirk G, Donfield SM, Buchbinder S, Khakoo SI, Goedert JJ, Trowsdale J, Carrington M, Kollnberger S, Asquith Ret al., 2018, Inhibitory killer-cell immunoglobulin-like receptors strengthen CD8+ T cell-mediated control of HIV-1, HCV and HTLV-1, Science Immunology, Vol: 3, Pages: 1-16, ISSN: 2470-9468

Killer cell immunoglobulin-like receptors (KIRs) are expressed predominantly on natural killer cells, where they play a key role in the regulation of innate immune responses. Recent studies show that inhibitory KIRs can also affect adaptive T cell–mediated immunity. In mice and in human T cells in vitro, inhibitory KIR ligation enhanced CD8+ T cell survival. To investigate the clinical relevance of these observations, we conducted an extensive immunogenetic analysis of multiple independent cohorts of HIV-1–, hepatitis C virus (HCV)–, and human T cell leukemia virus type 1 (HTLV-1)–infected individuals in conjunction with in vitro assays of T cell survival, analysis of ex vivo KIR expression, and mathematical modeling of host-virus dynamics. Our data suggest that functional engagement of inhibitory KIRs enhances the CD8+ T cell response against HIV-1, HCV, and HTLV-1 and is a significant determinant of clinical outcome in all three viral infections.

Journal article

Fernandez N, Makinde J, Black SL, Hayes P, King DF, Joseph S, McGowan E, Abel B, Gilmour Jet al., 2018, The Generation and Validation of Autologous CD8 and CD4 T Cell Lines for Use as Assay Controls in HIV Viral Inhibition Assays, HIV Research for Prevention Meeting (HIVR4P) - AIDS Vaccine, Microbicide and ARV-Based Prevention Science, Publisher: MARY ANN LIEBERT, INC, Pages: 247-247, ISSN: 0889-2229

Conference paper

Makinde J, Nduati EW, Kibirige C, Black SL, Hayes P, Hare J, King DF, Joseph S, McGowan E, Abel B, Price MA, Sanders EJ, Gilmour Jet al., 2018, Classification of HIV Controllers in an Acute Infection Cohort to Enable Systems Investigation of Signatures Associated With Control of Infection, HIV Research for Prevention Meeting (HIVR4P) - AIDS Vaccine, Microbicide and ARV-Based Prevention Science, Publisher: MARY ANN LIEBERT, INC, Pages: 377-377, ISSN: 0889-2229

Conference paper

Makinde J, Hayes P, Black SL, King DF, Joseph S, McGowan E, Abel B, Gilmour Jet al., 2018, A Rapid Protocol for Enriching Peptide-specific CD8 T Cell Lines to Determine Their Contribution to Viral Inhibition, HIV Research for Prevention Meeting (HIVR4P) - AIDS Vaccine, Microbicide and ARV-Based Prevention Science, Publisher: MARY ANN LIEBERT, INC, Pages: 246-246, ISSN: 0889-2229

Conference paper

Kvirkvelia N, Chikadze N, Makinde J, McBride JD, Porakishvili N, Hills FA, Martensen PM, Justesen J, Delves PJ, Lund T, Roitt IMet al., 2018, Investigation of factors influencing the immunogenicity of hCG as a potential cancer vaccine, CLINICAL AND EXPERIMENTAL IMMUNOLOGY, Vol: 193, Pages: 73-83, ISSN: 0009-9104

Journal article

Miles JJ, Tan MP, Dolton G, Edwards ESJ, Galloway SAE, Laugel B, Clement M, Makinde J, Ladell K, Matthews KK, Watkins TS, Tungatt K, Wong Y, Lee HS, Clark RJ, Pentier JM, Attaf M, Lissina A, Ager A, Gallimore A, Rizkallah PJ, Gras S, Rossjohn J, Burrows SR, Cole DK, Price DA, Sewell AKet al., 2018, Peptide mimic for influenza vaccination using nonnatural combinatorial chemistry, JOURNAL OF CLINICAL INVESTIGATION, Vol: 128, Pages: 1569-1580, ISSN: 0021-9738

Polypeptide vaccines effectively activate human T cells but suffer from poor biological stability, which confines both transport logistics and in vivo therapeutic activity. Synthetic biology has the potential to address these limitations through the generation of highly stable antigenic “mimics” using subunits that do not exist in the natural world. We developed a platform based on D–amino acid combinatorial chemistry and used this platform to reverse engineer a fully artificial CD8+ T cell agonist that mirrored the immunogenicity profile of a native epitope blueprint from influenza virus. This nonnatural peptide was highly stable in human serum and gastric acid, reflecting an intrinsic resistance to physical and enzymatic degradation. In vitro, the synthetic agonist stimulated and expanded an archetypal repertoire of polyfunctional human influenza virus–specific CD8+ T cells. In vivo, specific responses were elicited in naive humanized mice by subcutaneous vaccination, conferring protection from subsequent lethal influenza challenge. Moreover, the synthetic agonist was immunogenic after oral administration. This proof-of-concept study highlights the power of synthetic biology to expand the horizons of vaccine design and therapeutic delivery.

Journal article

Makinde J, Jones C, Bartolf A, Sibeko S, Baden S, Cosgrove C, Shattock RJet al., 2018, Localized cyclical variations in immunoproteins in the female genital tract and the implications on the design and assessment of mucosal infection and therapies, AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Vol: 79, ISSN: 1046-7408

ProblemFluctuating hormones regulate reproductive processes in the female genital tract. Consequent changes in the local immunological environment are likely to affect cellular interaction with infectious agents and the assessment of therapies that target mucosal infections.Method of studyWe compared Softcup and Weck‐Cel sampling protocols and assessed the changes in the concentrations of 39 soluble proteins with menstrual cycle progression in the mucosal and peripheral compartments.ResultsWe demonstrate that the mucosal immunological profile is distinct from serum with inflammatory and migratory signatures that are localized throughout the cycle. The analytes highlighted in the mucosal compartment were generally highest at the follicular phase with a tendency to fall as the cycle progressed through ovulation to the luteal phase.ConclusionOur results underscore the need to consider these localized cyclical differences in studies aimed at assessing the outcome of disease and the efficacy of mucosal vaccines and other therapies.

Journal article

Wooldridge L, Morgan D, Pearson JA, Gras S, van den Berg H, Lissina A, Llewellyn-Lacey S, Willis M, Dockree T, McLaren JE, Ekeruche-Makinde J, Gostick E, Robertson N, Rossjohn J, Burrows SR, Price D, Wong S, Peakman M, Skowera A, Clement Met al., 2017, Autoreactive CD8(+) T-cells are highly dependent on CD8 for activation and as such targeting CD8 is an effective way of blocking autoreactive CD8(+) T-cell activation, Annual Meeting of the American-Association-of-Immunologists (AAI), Publisher: AMER ASSOC IMMUNOLOGISTS, ISSN: 0022-1767

Conference paper

Cole DK, van den Berg HA, Lloyd A, Crowther MD, Beck K, Ekeruche-Makinde J, Miles JJ, Bulek AM, Dolton G, Schauenburg AJ, Wall A, Fuller A, Clement M, Laugel B, Rizkallah PJ, Wooldridge L, Sewell AKet al., 2016, Structural Mechanism Underpinning Cross-reactivity of a CD8(+) T-cell Clone That Recognizes a Peptide Derived from Human Telomerase Reverse Transcriptase, Journal of Biological Chemistry, Vol: 292, Pages: 802-813, ISSN: 0021-9258

T-cell cross-reactivity is essential for effective immune surveillance but has also been implicated as a pathway to autoimmunity. Previous studies have demonstrated that T-cell receptors (TCRs) that focus on a minimal motif within the peptide are able to facilitate a high level of T-cell cross-reactivity. However, the structural database shows that most TCRs exhibit less focused antigen binding involving contact with more peptide residues. To further explore the structural features that allow the clonally expressed TCR to functionally engage with multiple peptide-major histocompatibility complexes (pMHCs), we examined the ILA1 CD8+ T-cell clone that responds to a peptide sequence derived from human telomerase reverse transcriptase. The ILA1 TCR contacted its pMHC with a broad peptide binding footprint encompassing spatially distant peptide residues. Despite the lack of focused TCR-peptide binding, the ILA1 T-cell clone was still cross-reactive. Overall, the TCR-peptide contacts apparent in the structure correlated well with the level of degeneracy at different peptide positions. Thus, the ILA1 TCR was less tolerant of changes at peptide residues that were at, or adjacent to, key contact sites. This study provides new insights into the molecular mechanisms that control T-cell cross-reactivity with important implications for pathogen surveillance, autoimmunity, and transplant rejection.

Journal article

Makinde J, 2016, Eradicating polio amidst insurgency in Nigeria, Eradicating polio amidst insurgency in Nigeria

Speed read:Nigeria is now striving for polio eradication following four new cases.The new cases have led to unconventional strategies for vaccine coverage.But dealing decisively with Boko Haram insurgency could help achieve eradication.

Report

Clement M, Pearson JA, Gras S, van den Berg HA, Lissina A, Llewellyn-Lacey S, Willis MD, Dockree T, McLaren JE, Ekeruche-Makinde J, Gostick E, Robertson NP, Rossjohn J, Burrows SR, Price DA, Wong FS, Peakman M, Skowera A, Wooldridge Let al., 2016, Targeted suppression of autoreactive CD8(+) T-cell activation using blocking anti-CD8 antibodies, Scientific Reports, Vol: 6, ISSN: 2045-2322

CD8+ T-cells play a role in the pathogenesis of autoimmune diseases such as multiple sclerosis and type 1 diabetes. However, drugs that target the entire CD8+ T-cell population are not desirable because the associated lack of specificity can lead to unwanted consequences, most notably an enhanced susceptibility to infection. Here, we show that autoreactive CD8+ T-cells are highly dependent on CD8 for ligand-induced activation via the T-cell receptor (TCR). In contrast, pathogen-specific CD8+ T-cells are relatively CD8-independent. These generic differences relate to an intrinsic dichotomy that segregates self-derived and exogenous antigen-specific TCRs according to the monomeric interaction affinity with cognate peptide-major histocompatibility complex class I (pMHCI). As a consequence, “blocking” anti-CD8 antibodies can suppress autoreactive CD8+ T-cell activation in a relatively selective manner. These findings provide a rational basis for the development and in vivo assessment of novel therapeutic strategies that preferentially target disease-relevant autoimmune responses within the CD8+ T-cell compartment.

Journal article

Ekeruche-Makinde J, Herrera C, Evans A, Bosquet N, Le Grand R, Kelly C, Shattock Ret al., 2016, Targeting Cellular Drug Transporters to Boost Antiretroviral Drug Activity at Mucosal Sites, Conference on HIV Research for Prevention (HIV R4P), Publisher: MARY ANN LIEBERT, INC, Pages: 221-221, ISSN: 0889-2229

Conference paper

Szomolay B, Liu J, Brown PE, Miles JJ, Clement M, Llewellyn-Lacey S, Dolton G, Ekeruche-Makinde J, Lissina A, Schauenburg AJ, Sewell AK, Burrows SR, Roederer M, Price DA, Wooldridge L, van den Berg HAet al., 2016, Identification of human viral protein-derived ligands recognized by individual MHCI-restricted T-cell receptors, IMMUNOLOGY AND CELL BIOLOGY, Vol: 94, Pages: 573-582, ISSN: 0818-9641

Journal article

McDonald JU, Ekeruche-Makinde J, Ho MM, Tregoning JS, Ashiru Oet al., 2016, Development of a custom pentaplex sandwich immunoassay using Protein-G coupled beads for the Luminex® xMAP® platform., Journal of Immunological Methods, Vol: 433, Pages: 6-16, ISSN: 1872-7905

Multiplex bead-based assays have many advantages over ELISA, particularly for the analyses of large quantities of samples and/or precious samples of limited volume. Although many commercial arrays covering multitudes of biologically significant analytes are available, occasionally the development of custom arrays is necessary. Here, the development of a custom pentaplex sandwich immunoassay using Protein G-coupled beads, for analysis using the Luminex® xMAP® platform, is described. This array was required for the measurement of candidate biomarkers of vaccine safety in small volumes of mouse sera. Optimisation of this assay required a stepwise approach: testing cross-reactivity of the antibody pairs, the development of an in-house serum diluent buffer as well as heat-inactivation of serum samples to prevent interference from matrix effects. We then demonstrate the use of this array to analyse inflammatory mediators in mouse serum after immunisation. The work described here exemplifies how Protein G-coupled beads offer a flexible and robust approach to develop custom multiplex immunoassays, which can be applied to a range of analytes from multiple species.

Journal article

Mukhopadhya I, Murray GI, Berry S, Thomson J, Frank B, Gwozdz G, Ekeruche-Makinde J, Shattock R, Kelly C, Iannelli F, Pozzi G, El-Omar EM, Hold GL, Hijazi Ket al., 2016, Drug transporter gene expression in human colorectal tissue and cell lines: modulation with antiretrovirals for microbicide optimization, JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, Vol: 71, Pages: 372-386, ISSN: 0305-7453

Journal article

Singanayagam A, Lamb L, Makinde JE, Teo I, Shaunak Set al., 2015, Systemic cytokine storm in severe eosinophilic dermatitis, QJM-AN INTERNATIONAL JOURNAL OF MEDICINE, Vol: 108, Pages: 907-908, ISSN: 1460-2725

Journal article

Hijazi K, Cuppone AM, Smith K, Stincarelli MA, Ekeruche-Makinde J, De Falco G, Hold GL, Shattock R, Kelly CG, Pozzi G, Iannelli Fet al., 2015, Expression of Genes for Drug Transporters in the Human Female Genital Tract and Modulatory Effect of Antiretroviral Drugs, PLOS ONE, Vol: 10, ISSN: 1932-6203

Journal article

Reynolds C, Goudet A, Jenjaroen K, Sumonwiriya M, Rinchai D, Musson J, Overbeek S, Makinde J, Quigley K, Manji J, Spink N, Yos P, Wuthiekanun V, Bancroft G, Robinson J, Lertmemongkolchai G, Dunachie S, Maillere B, Holden M, Altmann D, Boyton Ret al., 2015, T cell immunity to the Alkyl Hydroperoxide Reductase of Burkholderia pseudomallei: A correlate of disease outcome in Acute Melioidosis., Journal of Immunology, Vol: 194, Pages: 4814-4824, ISSN: 0022-1767

There is an urgent need for a better understanding of adaptive immunity to Burkholderia pseudomallei, the causative agent of melioidosis that is frequently associated with sepsis or death in patients in Southeast Asia and Northern Australia. The imperative to identify vaccine targets is driven both by the public health agenda in these regions and biological threat concerns. In several intracellular bacterial pathogens, alkyl hydroperoxidase reductases are upregulated as part of the response to host oxidative stress, and they can stimulate strong adaptive immunity. We show that alkyl hydroperoxidase reductase (AhpC) of B. pseudomallei is strongly immunogenic for T cells of 'humanized' HLA transgenic mice and seropositive human donors. Some T cell epitopes, such as p6, are able to bind diverse HLA class II heterodimers and stimulate strong T cell immunity in mice and humans. Importantly, patients with acute melioidosis who survive infection show stronger T cell responses to AhpC relative to those who do not. Although the sequence of AhpC is virtually invariant among global B. pseudomallei clinical isolates, a Cambodian isolate varies only in C-terminal truncation of the p6 T cell epitope, raising the possibility of selection by host immunity. This variant peptide is virtually unable to stimulate T cell immunity. For an infection in which there has been debate about centrality of T cell immunity in defense, these observations support a role for T cell immunity to AhpC in disease protection.

Journal article

Miles J, van den Berg H, Ekeruche-Makinde J, Skowera A, Cole D, Dolton G, Schauenburg A, Tan MP, Pentier J, Peakman M, Price D, Burrows S, Sewell A, Wooldridge Let al., 2013, The length of the peptide in the MHC groove compartmentalizes the CD8+T cell repertoire, 100th Annual Meeting of the American-Association-of-Immunologists, Publisher: AMER ASSOC IMMUNOLOGISTS, ISSN: 0022-1767

Conference paper

Ekeruche-Makinde J, Miles JJ, van den Berg HA, Skowera A, Cole DK, Dolton G, Schauenburg AJA, Tan MP, Pentier JM, Llewellyn-Lacey S, Miles KM, Bulek AM, Clement M, Williams T, Trimby A, Bailey M, Rizkallah P, Rossjohn J, Peakman M, Price DA, Burrows SR, Sewell AK, Wooldridge Let al., 2013, Peptide length determines the outcome of TCR/peptide-MHCI engagement, BLOOD, Vol: 121, Pages: 1112-1123, ISSN: 0006-4971

Journal article

Ekeruche-Makinde J, Clement M, Cole DK, Edwards ESJ, Ladell K, Miles JJ, Matthews KK, Fuller A, Lloyd KA, Madura F, Dolton GM, Pentier J, Lissina A, Gostick E, Baxter TK, Baker BM, Rizkallah PJ, Price DA, Wooldridge L, Sewell AKet al., 2012, T-cell Receptor-optimized Peptide Skewing of the T-cell Repertoire Can Enhance Antigen Targeting, JOURNAL OF BIOLOGICAL CHEMISTRY, Vol: 287, Pages: 37269-37281

Journal article

Wooldridge L, Ekeruche-Makinde J, Skowera A, Peakman M, van den Berg HA, Sewell AKet al., 2012, A single autoimmune T cell receptor recognizes more than a million different peptides, European Congress of Immunology, Publisher: WILEY-BLACKWELL, Pages: 101-101, ISSN: 0019-2805

Conference paper

Wooldridge L, Ekeruche-Makinde J, van den Berg HA, Skowera A, Miles JJ, Tan MP, Dolton G, Clement M, Llewellyn-Lacey S, Price DA, Peakman M, Sewell AKet al., 2012, A Single Autoimmune T Cell Receptor Recognizes More Than a Million Different Peptides, JOURNAL OF BIOLOGICAL CHEMISTRY, Vol: 287, Pages: 1168-1177

Journal article

Pentier J, Dolton G, Ekeruche J, Schauenburg A, Wooldridge L, Rizkallah PJ, Miles JJ, Sewell AKet al., 2011, Making tumour-associated antigens more immunogenic; lessons from positional scanning synthetic combinatorial libraries, Annual Congress of the British-Society-for-Immunology, Publisher: WILEY-BLACKWELL, Pages: 59-59, ISSN: 0019-2805

Conference paper

Cole DK, Bulek A, Rizkallah P, Schauenburg A, Miles K, Edwards E, Madura F, Holland C, Godkin A, Doltan G, Laugel B, Bridgeman J, Pentier J, Tan M-P, Clement M, Miles J, Ladell K, Ekeruche J, Gostick E, Wooldridge L, McLaren J, Fuller A, Price D, Lissina A, Sewell Aet al., 2011, Structural and biophysical binding parameters that govern T-cell antigen discrimination, Annual Congress of the British-Society-for-Immunology, Publisher: WILEY-BLACKWELL, Pages: 53-53, ISSN: 0019-2805

Conference paper

Clement M, Ladell K, Ekeruche-Makinde J, Miles JJ, Edwards ESJ, Dolton G, Williams T, Schauenburg AJA, Cole DK, Lauder SN, Gallimore AM, Godkin AJ, Burrows SR, Price DA, Sewell AK, Wooldridge Let al., 2011, Anti-CD8 Antibodies Can Trigger CD8(+) T Cell Effector Function in the Absence of TCR Engagement and Improve Peptide-MHCI Tetramer Staining, JOURNAL OF IMMUNOLOGY, Vol: 187, Pages: 654-663, ISSN: 0022-1767

Journal article

Wooldridge L, Edwards E, Ekeruche J, Miles J, van den Berg H, Clement M, Sewell Aet al., 2011, Combinatorial peptide library scans of multiple HLA A*0201 restricted CTL reveal high levels of degeneracy at MHCI anchor positions, Publisher: AMER ASSOC IMMUNOLOGISTS, ISSN: 0022-1767

Conference paper

Ekeruche J, Clement M, Cole DK, Ladell K, Edwards E, Miles J, Wynn K, Fuller A, Lissina A, Gostick E, Baxter T, Baker B, Rizkallah P, Price D, Wooldridge L, Sewell AKet al., 2010, TOPSORT: TCR optimized peptide skewing of the repertoire of T-cells, Annual Congress of the British-Society-for-Immunology, Publisher: WILEY-BLACKWELL PUBLISHING, INC, Pages: 14-14, ISSN: 0019-2805

Conference paper

Clement M, Ladell K, Ekeruche J, Dolton G, Miles JJ, Cole DK, Lauder SN, Miners KL, Gallagher K, Gallimore AM, Godkin AJ, Price DA, Sewell AK, Wooldridge Let al., 2010, Antibody mediated CD8 ligation in the absence of TCR engagement can induce CTL effector function and enhance pMHCI tetramer binding, Annual Congress of the British-Society-for-Immunology, Publisher: WILEY-BLACKWELL PUBLISHING, INC, Pages: 173-173, ISSN: 0019-2805

Conference paper

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