Machine learning-driven identification of serotype-independent pneumococcal vaccine candidates using samples from human infection challenge studies
Vaccine, vol. 75, pp. 128280
Abstract
Identifying conserved, immunogenic proteins that confer protection against Streptococcus pneumoniae (pneumococcus) colonization could enable development of serotype-independent vaccines. In our controlled human infection model, no individual IgG or cytokine/chemokine response correlated significantly with protection against colonization with pneumococcus, suggesting that effective immunity reflects a coordinated, multi-antigen response. To capture these complex patterns, we trained independent Random Forest models on humoral and cellular datasets. The humoral model identified IgG responses to PdB, SP1069, and SP0899 as predictive of protection. The cellular model revealed that MCP-1 responses to SP1069 and SP0899, and IL-17A production in response to SP0648-3, were associated with protection. Elevated baseline IFN-γ, RANTES, and anti-protein IgG levels were linked to reduced colonization density. We highlight SP1069 and SP0899 as potential serotype-independent vaccine candidates and demonstrate the utility of machine learning to identify immune correlates of protection.
Authors 21
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University of London · Liverpool School of Tropical Medicine · City St George's, University of London
Affiliation as printed
Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom; City St George's, University of London, London, United Kingdom
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Liverpool School of Tropical Medicine · University of Oxford · NIHR Oxford Biomedical Research Centre
Affiliation as printed
Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, United Kingdom; NIHR Oxford Biomedical Research Centre, Oxford, United Kingdom
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Liverpool School of Tropical Medicine · London School of Hygiene & Tropical Medicine
Affiliation as printed
Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom; London School of Hygiene and Tropical Medicine, London, United Kingdom
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Liverpool School of Tropical Medicine · University of Oxford · NIHR Oxford Biomedical Research Centre
Affiliation as printed
Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, United Kingdom; NIHR Oxford Biomedical Research Centre, Oxford, United Kingdom
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Liverpool School of Tropical Medicine · University of Oxford · NIHR Oxford Biomedical Research Centre
Affiliation as printed
Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, United Kingdom; NIHR Oxford Biomedical Research Centre, Oxford, United Kingdom
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The University of Melbourne · Liverpool School of Tropical Medicine · Peter Doherty Institute · Murdoch Children's Research Institute
Affiliation as printed
Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom; Infection, Immunity and Global Health, Murdoch Children's Research Institute, Melbourne, Victoria, Australia; Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia
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Liverpool School of Tropical Medicine
Affiliation as printed
Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom; BioGrad Limited, Liverpool, United Kingdom
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Affiliation as printed
Laboratório de Bacteriologia, Instituto Butantan, São Paulo, Brazil
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Affiliation as printed
Laboratório de Bacteriologia, Instituto Butantan, São Paulo, Brazil
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Liverpool School of Tropical Medicine · University of Oxford · NIHR Oxford Biomedical Research Centre
Affiliation as printed
Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, United Kingdom; NIHR Oxford Biomedical Research Centre, Oxford, United Kingdom
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Liverpool School of Tropical Medicine · Liverpool University Hospitals NHS Foundation Trust
Affiliation as printed
Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom; Liverpool University Foundation Hospitals Trust, Liverpool, United Kingdom
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Universidade de São Paulo · Hospital Israelita Albert Einstein
Affiliation as printed
Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil, 05508; Hospital Israelita Albert Einstein, São Paulo, Brazil
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Liverpool School of Tropical Medicine · Centre for Inflammation Research · University of Edinburgh
Affiliation as printed
Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom; Centre for Inflammation Research, University of Edinburgh, Edinburgh, United Kingdom
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Boston Children's Hospital · Harvard University
Affiliation as printed
Boston Children's Hospital, Harvard, Medical School, MA, USA
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Liverpool School of Tropical Medicine
Affiliation as printed
Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom
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University of Oxford · NIHR Oxford Biomedical Research Centre
Affiliation as printed
Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, United Kingdom; NIHR Oxford Biomedical Research Centre, Oxford, United Kingdom
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Boston Children's Hospital · Harvard University
Affiliation as printed
Boston Children's Hospital, Harvard, Medical School, MA, USA
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Simon P. Jochems Aachen
Leiden University · Leiden University Medical Center
Affiliation as printed
Leiden University Center for Infectious Diseases (LUCID), Leiden University Medical Center, Leiden, Netherlands
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Liverpool School of Tropical Medicine · University of Oxford · NIHR Oxford Biomedical Research Centre
Affiliation as printed
Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, United Kingdom; NIHR Oxford Biomedical Research Centre, Oxford, United Kingdom
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Carla Solórzano corresponding
Liverpool School of Tropical Medicine · University of Oxford · NIHR Oxford Biomedical Research Centre
Affiliation as printed
Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, United Kingdom; NIHR Oxford Biomedical Research Centre, Oxford, United Kingdom. Electronic address: carla.solorzanogonzalez@paediatrics.ox.ac.uk
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Liverpool School of Tropical Medicine · University of Oxford
Affiliation as printed
Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, United Kingdom
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