Machine Learning-Driven Identification of Serotype-Independent Pneumococcal Vaccine Candidates using samples from Human Infection Challenge Studies

medRxiv

Abstract

Abstract Identifying conserved, immunogenic proteins that confer protection against Streptococcus pneumoniae colonisation could enable development of serotype-independent vaccines. We analysed baseline samples from 86 healthy adults experimentally challenged with pneumococcal serotypes 6B or 15B to investigate whether immune responses to 75 universally expressed pneumococcal proteins associated with protection against colonisation. We measured serum IgG using a novel Luminex assay and cytokine responses from peripheral blood mononuclear cells following antigen stimulation. No individual IgG or cytokine marker correlated significantly with protection in univariate analysis. However, machine learning identified IgG responses to PdB, SP1069, and SP0899 as predictive of protection. MCP-1 responses to SP1069 and SP0899, and IL-17 production in response to SP0648-3 also correlated with protection. Elevated baseline IFN-γ, RANTES, and anti-protein IgG correlated with lower colonisation 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. Graphical Abstract

Authors 20

1. Katerina S. Cheliotis

   City St George's, University of London

   Affiliation as printed

   City St George's, University of London;

2. Patrícia Gonzalez‐Dias

   University of Oxford

   Affiliation as printed

   Oxford Vaccine Group, Department of Paediatrics, University of Oxford;

3. Esther L. German

   London School of Hygiene & Tropical Medicine

   Affiliation as printed

   London School of Hygeine and Tropical Medicine;

4. André N. A. Gonçalves

   University of Oxford

   Affiliation as printed

   Oxford Vaccine Group, Department of Paediatrics, University of Oxford;

5. Elena Mitsi

   University of Oxford

   Affiliation as printed

   Oxford Vaccine Group, Department of Paediatrics, University of Oxford;

6. Elissavet Nikolaou

   Murdoch Children's Research Institute

   Affiliation as printed

   Infection, Immunity and Global Health, Murdoch Childrens Research Institute, Melbourne;

7. Sherin Pojar
   Affiliation as printed

   BioGrad Limited, Liverpool;

8. Eliane Namie Miyaji

   Instituto Butantan

   Affiliation as printed

   Laboratório de Bacteriologia, Instituto Butantan;

9. Rafaella Tostes

   Instituto Butantan

   Affiliation as printed

   Laboratório de Bacteriologia, Instituto Butantan;

10. Jesús Reiné

    University of Oxford

    Affiliation as printed

    Oxford Vaccine Group, Department of Paediatrics, University of Oxford;

11. Andrea M. Collins

    University of Liverpool · Liverpool School of Tropical Medicine

    Affiliation as printed

    Department of Clinical Sciences, Liverpool School of Tropical Medicine;

12. Helder Imoto Nakaya

    Universidade de São Paulo

    Affiliation as printed

    Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo;

13. Stephen B. Gordon

    Centre for Inflammation Research · University of Edinburgh

    Affiliation as printed

    Centre for Inflammation Research, University of Edinburgh;

14. Ying‐Jie Lu

    Boston Children's Hospital · Harvard University

    Affiliation as printed

    Boston Children's Hospital, Harvard Medical School;

15. Shaun H. Pennington

    University of Liverpool · Liverpool School of Tropical Medicine

    Affiliation as printed

    Department of Clinical Sciences, Liverpool School of Tropical Medicine;

16. Richard Malley

    Boston Children's Hospital · Harvard University

    Affiliation as printed

    Boston Children's Hospital, Harvard Medical School;

17. Simon P. Jochems Aachen

    Leiden University · Leiden University Medical Center

    Affiliation as printed

    Leiden University Center for Infectious Diseases (LUCID), Leiden University Medical Center

18. Britta C. Urban

    University of Oxford

    Affiliation as printed

    Oxford Vaccine Group, Department of Paediatrics, University of Oxford;

19. Carla Solórzano

    University of Oxford

    Affiliation as printed

    Oxford Vaccine Group, Department of Paediatrics, University of Oxford;

20. Daniela Mulari Ferreira corresponding

    University of Oxford

    Affiliation as printed

    Oxford Vaccine Group, Department of Paediatrics, University of Oxford;