{
  "abstract": "Introduction Enteric fever, primarily caused by Salmonella enterica Typhi and Salmonella enterica Paratyphi A (SPA), is endemic mainly in South Asia, disproportionately affecting school-age children. Although typhoid conjugate vaccines (TCVs) are effective and implemented in many countries, no licensed vaccine exists against paratyphoid A. Bivalent vaccines targeting both S. Typhi and SPA may address this gap. Although field efficacy trials are not considered feasible, controlled human infection models (CHIMs) offer an alternative pathway for evaluating vaccine efficacy. This will be the first efficacy study of a bivalent vaccine against typhoid and paratyphoid A using a paratyphoid CHIM.Methods and analysis This is a phase II multicentre, double-blind, randomised controlled trial assessing the efficacy and immunogenicity of a bivalent conjugate vaccine candidate, Serum Institute of India Typhoid Conjugate Vaccine (Bivalent) (SII-TCV(B)), against SPA using a CHIM in healthy UK adults aged 18–55 years. A total of 192 participants will be randomised 1:1 to receive either SII-TCV(B) or a licensed Vi-polysaccharide typhoid vaccine (Vi-PS). All participants will be orally challenged with S. Paratyphi A (strain NVGH308) 28 days postvaccination. Participants will be monitored closely for 14 days and treated at 14 days postchallenge or promptly on diagnosis, according to prespecified criteria. The primary objective is to evaluate vaccine efficacy of SII-TCV(B) against paratyphoid infection using a CHIM. The coprimary immunogenicity objective is to assess non-inferiority of the typhoid IgG response compared with a licensed Vi-PS control.Ethics and dissemination The study has received ethical approval from the Berkshire Research Ethics Committee (24/SC/0309) and regulatory approval from the UK Medicines and Healthcare products Regulatory Agency. Results will be disseminated via peer-reviewed publications and scientific meetings.Trial registration number ISRCTN65855590.",
  "authors": [
    {
      "affiliations": [
        "University of Oxford Oxford Vaccine Group, Oxford, UK",
        "NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK"
      ],
      "name": "Margarete Paganotti Vicentine"
    },
    {
      "affiliations": [
        "University of Oxford Oxford Vaccine Group, Oxford, UK",
        "NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK"
      ],
      "name": "Naina McCann"
    },
    {
      "affiliations": [
        "University of Oxford Oxford Vaccine Group, Oxford, UK",
        "NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK"
      ],
      "name": "Oisin Hennigan"
    },
    {
      "affiliations": [
        "University of Oxford Oxford Vaccine Group, Oxford, UK",
        "NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK"
      ],
      "name": "Noshi Maria"
    },
    {
      "affiliations": [
        "University of Oxford Oxford Vaccine Group, Oxford, UK",
        "NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK"
      ],
      "name": "Claudia I Juarez Molina"
    },
    {
      "affiliations": [
        "University of Oxford Oxford Vaccine Group, Oxford, UK",
        "NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK"
      ],
      "name": "Stanislava Koleva"
    },
    {
      "affiliations": [
        "University of Oxford Oxford Vaccine Group, Oxford, UK",
        "Oxford Health NHS Foundation Trust, Oxford, UK"
      ],
      "name": "Mohammod K Islam"
    },
    {
      "affiliations": [
        "University of Oxford Oxford Vaccine Group, Oxford, UK"
      ],
      "name": "Elizabeth Jones"
    },
    {
      "affiliations": [
        "University of Oxford, Oxford, UK"
      ],
      "name": "Amy Flaxman"
    },
    {
      "affiliations": [
        "University of Oxford Oxford Vaccine Group, Oxford, UK",
        "Texas Department of Public Safety, Austin, Texas, USA"
      ],
      "name": "Nicole Day"
    },
    {
      "affiliations": [
        "University of Oxford Oxford Vaccine Group, Oxford, UK",
        "NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK"
      ],
      "name": "Allison MacDonald"
    },
    {
      "affiliations": [
        "University of Oxford Oxford Vaccine Group, Oxford, UK",
        "NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK"
      ],
      "name": "Mehreen Adnan"
    },
    {
      "affiliations": [
        "University of Oxford, Oxford, UK"
      ],
      "name": "Nisha Singh"
    },
    {
      "affiliations": [
        "University of Oxford Oxford Vaccine Group, Oxford, UK",
        "NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK"
      ],
      "name": "Sophie Vernon"
    },
    {
      "affiliations": [
        "University of Oxford Oxford Vaccine Group, Oxford, UK",
        "NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK"
      ],
      "name": "Eleanor Wilson"
    },
    {
      "affiliations": [
        "Serum Institute of India Private Limited, Pune, India"
      ],
      "name": "Anirudha Vyankatesh Potey"
    },
    {
      "affiliations": [
        "Serum Institute of India Private Limited, Pune, India"
      ],
      "name": "Abhijeet Dharmadhikari"
    },
    {
      "affiliations": [
        "Serum Institute of India Private Limited, Pune, India"
      ],
      "name": "Sanket Gaidhane"
    },
    {
      "affiliations": [
        "Serum Institute of India Private Limited, Pune, India"
      ],
      "name": "Prasad S Kulkarni"
    },
    {
      "affiliations": [
        "University of Oxford Oxford Vaccine Group, Oxford, UK",
        "NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK"
      ],
      "name": "Hannah Robinson"
    },
    {
      "affiliations": [
        "University of Oxford Oxford Vaccine Group, Oxford, UK",
        "NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK"
      ],
      "name": "Parvinder Aley"
    },
    {
      "affiliations": [
        "University of Oxford Oxford Vaccine Group, Oxford, UK",
        "NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK"
      ],
      "name": "Young Chan Kim"
    },
    {
      "affiliations": [
        "University of Oxford Oxford Vaccine Group, Oxford, UK",
        "NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK",
        "Oxford University Hospitals NHS Foundation Trust, Oxford, UK"
      ],
      "name": "Brian Angus"
    },
    {
      "affiliations": [
        "University of Oxford Oxford Vaccine Group, Oxford, UK",
        "NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK"
      ],
      "name": "Xinxue Liu"
    },
    {
      "affiliations": [
        "University of Oxford Oxford Vaccine Group, Oxford, UK",
        "NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK",
        "Oxford University Hospitals NHS Foundation Trust, Oxford, UK"
      ],
      "name": "Maheshi Nirmala Ramasamy"
    },
    {
      "affiliations": [
        "University of Oxford Oxford Vaccine Group, Oxford, UK",
        "NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK"
      ],
      "name": "Andrew J Pollard"
    }
  ],
  "title": "Phase II multicentre double-blind randomised controlled trial of a Bivalent VaccInation against Salmonella Typhi and Paratyphi A (BiVISTA) using a controlled human infection model of paratyphoid A infection: study protocol",
  "uid": "e956af81-ffdf-508a-a89f-6e3ca6c8f001"
}