Preliminary assessment of the efficacy of a T-cell-based influenza vaccine, MVA-NP+M1, in humans.

Abstract

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.

• Authors: Patrick J Lillie, Tamara K Berthoud, Timothy J Powell, Teresa Lambe, Caitlin Mullarkey, Alexandra J Spencer, Matthew Hamill, Yanchun Peng, Marie-Eve Blais, Christopher J A Duncan, Susanne H Sheehy, Tom Havelock, Saul N Faust, Rob Lambkin Williams, Anthony Gilbert, John Oxford, Tao Dong, Adrian V S Hill, Sarah C Gilbert
• Journal: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America (Clin Infect Dis) Vol. 55 Issue 1 Pg. 19-25 (Jul 2012) ISSN: 1537-6591 [Electronic] United States
• PMID: 22441650 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Viral
• Antigens, Viral
• HLA-A2 Antigen
• Influenza Vaccines
• M1 protein, Influenza A virus
• NP protein, Influenza A virus
• Nucleocapsid Proteins
• RNA-Binding Proteins
• Viral Core Proteins
• Viral Matrix Proteins
• Interferon-gamma

Topics

• Administration, Intranasal
• Adolescent
• Adult
• Antibodies, Viral (blood, immunology)
• Antigens, Viral (immunology)
• HLA-A2 Antigen
• Humans
• Influenza A virus (immunology)
• Influenza Vaccines (administration & dosage, adverse effects, immunology)
• Influenza, Human (immunology, prevention & control, virology)
• Interferon-gamma
• Middle Aged
• Nucleocapsid Proteins
• Pilot Projects
• RNA-Binding Proteins (immunology)
• T-Lymphocytes (immunology)
• Viral Core Proteins (immunology)
• Viral Matrix Proteins (immunology)
• Virus Shedding