Systemically administered DNA and fowlpox recombinants expressing four vaccinia virus genes although immunogenic do not protect mice against the highly pathogenic IHD-J vaccinia strain

Massimiliano Bissa, Sole Maria Pacchioni, Carlo Zanotto, Carlo De Giuli Morghen, Elena Illiano, Francesca Granucci, Ivan Zanoni, Achille Broggi, Antonia Radaelli

Research output: Contribution to journalArticle

Abstract

The first-generation smallpox vaccine was based on live vaccinia virus (VV) and it successfully eradicated the disease worldwide. Therefore, it was not administered any more after 1980, as smallpox no longer existed as a natural infection. However, emerging threats by terrorist organisations has prompted new programmes for second-generation vaccine development based on attenuated VV strains, which have been shown to cause rare but serious adverse events in immunocompromised patients. Considering the closely related animal poxviruses that might also be used as bioweapons, and the increasing number of unvaccinated young people and AIDS-affected immunocompromised subjects, a safer and more effective smallpox vaccine is still required. New avipoxvirus-based vectors should improve the safety of conventional vaccines, and protect from newly emerging zoonotic orthopoxvirus diseases and from the threat of deliberate release of variola or monkeypox virus in a bioterrorist attack. In this study, DNA and fowlpox recombinants expressing the L1R, A27L, A33R and B5R genes were constructed and evaluated in a pre-clinical trial in mouse, following six prime/boost immunisation regimens, to compare their immunogenicity and protective efficacy against a challenge with the lethal VV IHD-J strain. Although higher numbers of VV-specific IFNγ-producing T lymphocytes were observed in the protected mice, the cytotoxic T-lymphocyte response and the presence of neutralising antibodies did not always correlate with protection. In spite of previous successful results in mice, rabbits and monkeys, where SIV/HIV transgenes were expressed by the fowlpox vector, the immune response elicited by these recombinants was low, and most of the mice were not protected.

Original languageEnglish
Pages (from-to)374-382
Number of pages9
JournalVirus Research
Volume178
Issue number2
DOIs
Publication statusPublished - Dec 26 2013

Fingerprint

Fowlpox
Vaccinia
Recombinant DNA
Vaccinia virus
Smallpox Vaccine
Genes
Avipoxvirus
Monkeypox virus
Vaccines
Variola virus
Orthopoxvirus
Poxviridae
Smallpox
Zoonoses
Immunocompromised Host
Cytotoxic T-Lymphocytes
Neutralizing Antibodies
Transgenes
Haplorhini
Immunization

Keywords

  • Fowlpox virus
  • L1R, A27L, A33R and B5R VV genes
  • OPXV vaccine
  • Prime/boost
  • Recombinant vaccine

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases
  • Cancer Research

Cite this

Systemically administered DNA and fowlpox recombinants expressing four vaccinia virus genes although immunogenic do not protect mice against the highly pathogenic IHD-J vaccinia strain. / Bissa, Massimiliano; Pacchioni, Sole Maria; Zanotto, Carlo; De Giuli Morghen, Carlo; Illiano, Elena; Granucci, Francesca; Zanoni, Ivan; Broggi, Achille; Radaelli, Antonia.

In: Virus Research, Vol. 178, No. 2, 26.12.2013, p. 374-382.

Research output: Contribution to journalArticle

Bissa, Massimiliano ; Pacchioni, Sole Maria ; Zanotto, Carlo ; De Giuli Morghen, Carlo ; Illiano, Elena ; Granucci, Francesca ; Zanoni, Ivan ; Broggi, Achille ; Radaelli, Antonia. / Systemically administered DNA and fowlpox recombinants expressing four vaccinia virus genes although immunogenic do not protect mice against the highly pathogenic IHD-J vaccinia strain. In: Virus Research. 2013 ; Vol. 178, No. 2. pp. 374-382.
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