Journal Article

Preliminary Assessment of the Efficacy of a T-Cell-Based Influenza Vaccine, MVA-NP+M1, in Humans

Spencer, Alexandra J., Havelock, Tom, Powell, Timothy J., Oxford, John, Williams, Rob Lambkin, Lambe, Teresa, Peng, Yanchun, Hill, Adrian V. S., Blais, Marie-Eve, Lillie, Patrick J., Mullarkey, Caitlin, Gilbert, Sarah C., Berthoud, Tamara K., Duncan, Christopher J. A., Sheehy, Susanne H., Dong, Tao, Hamill, Matthew, Faust, Saul N., Gilbert, Anthony

2012

Overview

Background. The novel influenza vaccine MVA-NP+M1 is designed to boost cross-reactive T-cell responses to internal antigens of the influenza A virus that are conserved across all subtypes, providing protection against both influenza disease and virus shedding against all influenza A viruses. Following a phase 1 clinical study that demonstrated vaccine safety and immunogenicity, a phase 2a vaccination and influenza challenge study has been conducted in healthy adult volunteers. Methods. Volunteers with no measurable serum antibodies to influenza A/Wisconsin/67/2005 received either a single vaccination with MVA-NP+M1 or no vaccination. T-cell responses to the vaccine antigens were measured at enrollment and again prior to virus challenge. All volunteers underwent intranasal administration of influenza A/Wisconsin/67/2005 while in a quarantine unit and were monitored for symptoms of influenza disease and virus shedding. Results. Volunteers had a significantly increased T-cell response to the vaccine antigens following a single dose of the vaccine, with an increase in cytolytic effector molecules. Intranasal influenza challenge was undertaken without safety issues. Two of 11 vaccinees and 5 of 11 control subjects developed laboratory-confirmed influenza (symptoms plus virus shedding). Symptoms of influenza were less pronounced in the vaccinees and there was a significant reduction in the number of days of virus shedding in those vaccinees who developed influenza (mean, 1.09 days in controls, 0.45 days in vaccinees, P = .036). Conclusions. This study provides the first demonstration of clinical efficacy of a T-cell-based influenza vaccine and indicates that further clinical development should be undertaken. Clinical Trials Registration. NCT00993083.

• Publisher: Oxford University Press
• Subject: Administration, Intranasal / Adolescent / Adult / and Commentaries / Antibodies, Viral - blood / Antibodies, Viral - immunology / Antigens / Antigens, Viral - immunology / ARTICLES AND COMMENTARIES / Biological and medical sciences / Dosage / HLA-A2 Antigen / Human viral diseases / Humans / Immunization / Immunogenicity / Infectious diseases / Influenza / Influenza A virus / Influenza A virus - immunology / Influenza vaccines / Influenza Vaccines - administration & dosage / Influenza Vaccines - adverse effects / Influenza Vaccines - immunology / Influenza, Human - immunology / Influenza, Human - prevention & control / Influenza, Human - virology / Interferon-gamma / Medical sciences / Middle Aged / Nucleocapsid Proteins / Orthomyxoviridae / Patient safety / Pilot Projects / RNA-Binding Proteins - immunology / Symptoms / T lymphocytes / T-Lymphocytes - immunology / Vaccination / Vaccines / Viral Core Proteins - immunology / Viral diseases / Viral diseases of the respiratory system and ent viral diseases / Viral Matrix Proteins - immunology / Virus Shedding / Viruses / Volunteerism