Immunogenicity of modified vaccinia virus Ankara expressing the hemagglutinin stalk domain of pandemic (H1N1) 2009 influenza virus

Giuseppina Di Mario, Elisa Soprana, Francesco Gubinelli, Maddalena Panigada, Marzia Facchini, Concetta Fabiani, Bruno Garulli, Michela Basileo, Antonio Cassone, Antonio Siccardi, Isabella Donatelli, Maria R. Castrucci

Research output: Contribution to journalArticle

Abstract

Background: Vaccination offers protection against influenza, although current vaccines need to be reformulated each year. The development of a broadly protective influenza vaccine would guarantee the induction of heterosubtypic immunity also against emerging influenza viruses of a novel subtype. Vaccine candidates based on the stalk region of the hemagglutinin (HA) have the potential to induce broad and persistent protection against diverse influenza A viruses. Methods: Modified vaccinia virus Ankara (MVA) expressing a headless HA (hlHA) of A/California/4/09 (CA/09) virus was used as a vaccine to immunize C57BL/6 mice. Specific antibody and cell-mediated immune responses were determined, and challenge experiments were performed by infecting vaccinated mice with CA/09 virus. Results: Immunization of mice with CA/09-derived hlHA, vectored by MVA, was able to elicit influenza-specific broad cross-reactive antibodies and cell-mediated immune responses, but failed to induce neutralizing antibodies and did not protect mice against virus challenge. Conclusion: Although highly immunogenic, our vaccine was unable to induce a protective immunity against influenza. A misfolded and unstable conformation of the hlHA molecule may have affected its capacity of inducing neutralizing antiviral, conformational antibodies. Design of stable hlHA-based immunogens and their delivery by recombinant MVA-based vectors has the potential of improving this promising approach for a universal influenza vaccine.

Original languageEnglish
Pages (from-to)69-75
Number of pages7
JournalPathogens and Global Health
Volume111
Issue number2
DOIs
Publication statusPublished - Feb 17 2017

Fingerprint

Vaccinia virus
Hemagglutinins
Pandemics
Orthomyxoviridae
Vaccines
Human Influenza
Influenza Vaccines
Viruses
Antibodies
Immunity
Influenza A virus
Neutralizing Antibodies
Inbred C57BL Mouse
Antiviral Agents
Immunization
Vaccination

Keywords

  • antibodies
  • Influenza virus
  • MVA vector
  • vaccine

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

Cite this

Immunogenicity of modified vaccinia virus Ankara expressing the hemagglutinin stalk domain of pandemic (H1N1) 2009 influenza virus. / Di Mario, Giuseppina; Soprana, Elisa; Gubinelli, Francesco; Panigada, Maddalena; Facchini, Marzia; Fabiani, Concetta; Garulli, Bruno; Basileo, Michela; Cassone, Antonio; Siccardi, Antonio; Donatelli, Isabella; Castrucci, Maria R.

In: Pathogens and Global Health, Vol. 111, No. 2, 17.02.2017, p. 69-75.

Research output: Contribution to journalArticle

Di Mario, Giuseppina ; Soprana, Elisa ; Gubinelli, Francesco ; Panigada, Maddalena ; Facchini, Marzia ; Fabiani, Concetta ; Garulli, Bruno ; Basileo, Michela ; Cassone, Antonio ; Siccardi, Antonio ; Donatelli, Isabella ; Castrucci, Maria R. / Immunogenicity of modified vaccinia virus Ankara expressing the hemagglutinin stalk domain of pandemic (H1N1) 2009 influenza virus. In: Pathogens and Global Health. 2017 ; Vol. 111, No. 2. pp. 69-75.
@article{d7c80ad614ce4472ba0ec898e3faff79,
title = "Immunogenicity of modified vaccinia virus Ankara expressing the hemagglutinin stalk domain of pandemic (H1N1) 2009 influenza virus",
abstract = "Background: Vaccination offers protection against influenza, although current vaccines need to be reformulated each year. The development of a broadly protective influenza vaccine would guarantee the induction of heterosubtypic immunity also against emerging influenza viruses of a novel subtype. Vaccine candidates based on the stalk region of the hemagglutinin (HA) have the potential to induce broad and persistent protection against diverse influenza A viruses. Methods: Modified vaccinia virus Ankara (MVA) expressing a headless HA (hlHA) of A/California/4/09 (CA/09) virus was used as a vaccine to immunize C57BL/6 mice. Specific antibody and cell-mediated immune responses were determined, and challenge experiments were performed by infecting vaccinated mice with CA/09 virus. Results: Immunization of mice with CA/09-derived hlHA, vectored by MVA, was able to elicit influenza-specific broad cross-reactive antibodies and cell-mediated immune responses, but failed to induce neutralizing antibodies and did not protect mice against virus challenge. Conclusion: Although highly immunogenic, our vaccine was unable to induce a protective immunity against influenza. A misfolded and unstable conformation of the hlHA molecule may have affected its capacity of inducing neutralizing antiviral, conformational antibodies. Design of stable hlHA-based immunogens and their delivery by recombinant MVA-based vectors has the potential of improving this promising approach for a universal influenza vaccine.",
keywords = "antibodies, Influenza virus, MVA vector, vaccine",
author = "{Di Mario}, Giuseppina and Elisa Soprana and Francesco Gubinelli and Maddalena Panigada and Marzia Facchini and Concetta Fabiani and Bruno Garulli and Michela Basileo and Antonio Cassone and Antonio Siccardi and Isabella Donatelli and Castrucci, {Maria R.}",
year = "2017",
month = "2",
day = "17",
doi = "10.1080/20477724.2016.1275464",
language = "English",
volume = "111",
pages = "69--75",
journal = "Pathogens and Global Health",
issn = "2047-7724",
publisher = "Maney Publishing",
number = "2",

}

TY - JOUR

T1 - Immunogenicity of modified vaccinia virus Ankara expressing the hemagglutinin stalk domain of pandemic (H1N1) 2009 influenza virus

AU - Di Mario, Giuseppina

AU - Soprana, Elisa

AU - Gubinelli, Francesco

AU - Panigada, Maddalena

AU - Facchini, Marzia

AU - Fabiani, Concetta

AU - Garulli, Bruno

AU - Basileo, Michela

AU - Cassone, Antonio

AU - Siccardi, Antonio

AU - Donatelli, Isabella

AU - Castrucci, Maria R.

PY - 2017/2/17

Y1 - 2017/2/17

N2 - Background: Vaccination offers protection against influenza, although current vaccines need to be reformulated each year. The development of a broadly protective influenza vaccine would guarantee the induction of heterosubtypic immunity also against emerging influenza viruses of a novel subtype. Vaccine candidates based on the stalk region of the hemagglutinin (HA) have the potential to induce broad and persistent protection against diverse influenza A viruses. Methods: Modified vaccinia virus Ankara (MVA) expressing a headless HA (hlHA) of A/California/4/09 (CA/09) virus was used as a vaccine to immunize C57BL/6 mice. Specific antibody and cell-mediated immune responses were determined, and challenge experiments were performed by infecting vaccinated mice with CA/09 virus. Results: Immunization of mice with CA/09-derived hlHA, vectored by MVA, was able to elicit influenza-specific broad cross-reactive antibodies and cell-mediated immune responses, but failed to induce neutralizing antibodies and did not protect mice against virus challenge. Conclusion: Although highly immunogenic, our vaccine was unable to induce a protective immunity against influenza. A misfolded and unstable conformation of the hlHA molecule may have affected its capacity of inducing neutralizing antiviral, conformational antibodies. Design of stable hlHA-based immunogens and their delivery by recombinant MVA-based vectors has the potential of improving this promising approach for a universal influenza vaccine.

AB - Background: Vaccination offers protection against influenza, although current vaccines need to be reformulated each year. The development of a broadly protective influenza vaccine would guarantee the induction of heterosubtypic immunity also against emerging influenza viruses of a novel subtype. Vaccine candidates based on the stalk region of the hemagglutinin (HA) have the potential to induce broad and persistent protection against diverse influenza A viruses. Methods: Modified vaccinia virus Ankara (MVA) expressing a headless HA (hlHA) of A/California/4/09 (CA/09) virus was used as a vaccine to immunize C57BL/6 mice. Specific antibody and cell-mediated immune responses were determined, and challenge experiments were performed by infecting vaccinated mice with CA/09 virus. Results: Immunization of mice with CA/09-derived hlHA, vectored by MVA, was able to elicit influenza-specific broad cross-reactive antibodies and cell-mediated immune responses, but failed to induce neutralizing antibodies and did not protect mice against virus challenge. Conclusion: Although highly immunogenic, our vaccine was unable to induce a protective immunity against influenza. A misfolded and unstable conformation of the hlHA molecule may have affected its capacity of inducing neutralizing antiviral, conformational antibodies. Design of stable hlHA-based immunogens and their delivery by recombinant MVA-based vectors has the potential of improving this promising approach for a universal influenza vaccine.

KW - antibodies

KW - Influenza virus

KW - MVA vector

KW - vaccine

UR - http://www.scopus.com/inward/record.url?scp=85010637384&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85010637384&partnerID=8YFLogxK

U2 - 10.1080/20477724.2016.1275464

DO - 10.1080/20477724.2016.1275464

M3 - Article

C2 - 28081672

AN - SCOPUS:85010637384

VL - 111

SP - 69

EP - 75

JO - Pathogens and Global Health

JF - Pathogens and Global Health

SN - 2047-7724

IS - 2

ER -