Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2012 Jul;55(1):19-25.
doi: 10.1093/cid/cis327. Epub 2012 Mar 22.

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

Affiliations
Clinical Trial

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

Patrick J Lillie et al. Clin Infect Dis. 2012 Jul.

Erratum in

  • Erratum.
    [No authors listed] [No authors listed] Clin Infect Dis. 2019 Jun 18;69(1):195. doi: 10.1093/cid/ciz354. Clin Infect Dis. 2019. PMID: 31120522 Free PMC article. No abstract available.

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.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Ex vivo interferon γ enzyme-linked immunosorbent spot assay responses to nucleoprotein (NP) and matrix protein 1 (M1). The graph represents the summed response to NP and M1 antigens in vaccinees (circles) and controls (squares) at the relevant time points; lines represent the median per group and open symbols represent subjects who developed laboratory-confirmed influenza. Control subjects were not assayed at day 0 or day 21. Vaccination took place on day 0 and influenza challenge on day 30. Data were analyzed with a Kruskal-Wallis 1-way analysis of variance with selected pairs of data analyzed with a Dunn positive test. No significant difference between the median response in the vaccinated and control group was observed at time of screening (day 0 for vaccinees, day 29 for controls). A significant increase in the response was observed in vaccinees between days 0 and 21 and days 0 and 29 (< .001, < .05, respectively). A significant difference between vaccinees and controls was observed at day 29 (P < .05). Abbreviations: PBMC, peripheral blood mononuclear cell; SFU, spot-forming units.
Figure 2.
Figure 2.
Responses to M158–66 in human leukocyte antigen A2–positive volunteers. Whole blood drawn 1 day prior to virus challenge was labeled for tetramer (A*0201/GILGFVFTL) followed by perforin or granzyme A staining. Values shown are the percentage of CD8+ T cells or Tet+ cells; individuals are shown as a single point with lines representing the median per group. Open symbols represent samples from volunteers who subsequently developed laboratory-confirmed influenza. For each marker the data were analyzed with an unpaired t test; P values are shown for statistically significant differences between vaccinees and controls.
Figure 3.
Figure 3.
Total of symptom scores at each time point following challenge (A) or total grade 2 and 3 symptom and examination scores (B) for vaccinees (circles) and controls (squares), with the group mean indicated by a line. Open symbols denote subjects who developed laboratory-confirmed influenza after challenge.

References

    1. Osterholm MT, Kelley NS, Sommer A, Belongia EA. Efficacy and effectiveness of influenza vaccines: a systematic review and meta-analysis. Lancet Infect Dis. 2012;12:36–44. - PubMed
    1. Kresse H, Rovini H. Influenza vaccine market dynamics. Nat Rev Drug Discov. 2009;8:841–2. - PubMed
    1. McMichael AJ, Gotch F, Cullen P, Askonas B, Webster RG. The human cytotoxic T cell response to influenza A vaccination. Clin Exp Immunol. 1981;43:276–84. - PMC - PubMed
    1. Epstein SL. Prior H1N1 influenza infection and susceptibility of Cleveland Family Study participants during the H2N2 pandemic of 1957: an experiment of nature. J Infect Dis. 2006;193:49–53. - PubMed
    1. He XS, Holmes TH, Zhang C, et al. Cellular immune responses in children and adults receiving inactivated or live attenuated influenza vaccines. J Virol. 2006;80:11756–66. - PMC - PubMed

Publication types

MeSH terms

Associated data