The control of smallpox was achieved using live vaccinia virus (VV) vaccine, which successfully eradicated the disease worldwide. As the variola virus no longer exists as a natural infection agent, mass vaccination was discontinued after 1980. However, emergence of smallpox outbreaks caused by accidental or deliberate release of variola virus has stimulated new research for second-generation vaccine development based on attenuated VV strains. Considering the closely related animal poxviruses that also arise as zoonoses, and the increasing number of unvaccinated or immunocompromised people, a safer and more effective vaccine is still required. With this aim, new vectors based on avian poxviruses that cannot replicate in mammals should improve the safety of conventional vaccines, and protect from zoonotic orthopoxvirus diseases, such as cowpox and monkeypox. In this study, DNA and fowlpox (FP) recombinants that expressed the VV L1R, A27L, A33R, and B5R genes were generated (4DNAmix, 4FPmix, respectively) and tested in mice using novel administration routes. Mice were primed with 4DNAmix by electroporation, and boosted with 4FPmix applied intranasally. The lethal VVIHD-J strain was then administered by intranasal challenge. All of the mice receiving 4DNAmix followed by 4FPmix, and 20% of the mice immunized only with 4FPmix, were protected. The induction of specific humoral and cellular immune responses directly correlated with this protection. In particular, higher anti-A27 antibodies and IFN-producing T lymphocytes were measured in the blood and spleen of the protected mice, as compared to controls. VVIHD-J neutralizing antibodies in sera from the protected mice suggest that the prime/ boost vaccination regimen with 4DNAmix plus 4FPmix may be an effective and safe mode to induce protection against smallpox and poxvirus zoonotic infections. The electroporation/ intranasal administration routes contributed to effective immune responses and mouse survival.

Protection of mice against the highly pathogenic VVIHD-J by DNA and fowlpox recombinant vaccines, administered by electroporation and intranasal routes, correlates with serum neutralizing activity

QUAGLINO, Elena
Co-first
;
ROLIH, VALERIA;CAVALLO, Federica;
2016-01-01

Abstract

The control of smallpox was achieved using live vaccinia virus (VV) vaccine, which successfully eradicated the disease worldwide. As the variola virus no longer exists as a natural infection agent, mass vaccination was discontinued after 1980. However, emergence of smallpox outbreaks caused by accidental or deliberate release of variola virus has stimulated new research for second-generation vaccine development based on attenuated VV strains. Considering the closely related animal poxviruses that also arise as zoonoses, and the increasing number of unvaccinated or immunocompromised people, a safer and more effective vaccine is still required. With this aim, new vectors based on avian poxviruses that cannot replicate in mammals should improve the safety of conventional vaccines, and protect from zoonotic orthopoxvirus diseases, such as cowpox and monkeypox. In this study, DNA and fowlpox (FP) recombinants that expressed the VV L1R, A27L, A33R, and B5R genes were generated (4DNAmix, 4FPmix, respectively) and tested in mice using novel administration routes. Mice were primed with 4DNAmix by electroporation, and boosted with 4FPmix applied intranasally. The lethal VVIHD-J strain was then administered by intranasal challenge. All of the mice receiving 4DNAmix followed by 4FPmix, and 20% of the mice immunized only with 4FPmix, were protected. The induction of specific humoral and cellular immune responses directly correlated with this protection. In particular, higher anti-A27 antibodies and IFN-producing T lymphocytes were measured in the blood and spleen of the protected mice, as compared to controls. VVIHD-J neutralizing antibodies in sera from the protected mice suggest that the prime/ boost vaccination regimen with 4DNAmix plus 4FPmix may be an effective and safe mode to induce protection against smallpox and poxvirus zoonotic infections. The electroporation/ intranasal administration routes contributed to effective immune responses and mouse survival.
2016
134
182
191
www.elsevier.com/locate/antiviral
Fowlpox virus; Intranasal mucosal vaccination; L1R, A27L, A33R, B5R VV genes; OPXV vaccine; Prime/boost; Recombinant vaccines; Pharmacology; Virology
Bissa, Massimiliano; Quaglino, Elena; Zanotto, Carlo; Illiano, Elena; Rolih, Valeria; Pacchioni, Sole; Cavallo, Federica; De Giuli Morghen, Carlo; Rad...espandi
File in questo prodotto:
File Dimensione Formato  
Bissa et al., Antiviral Res, 2016.pdf

Accesso aperto

Tipo di file: PDF EDITORIALE
Dimensione 982.98 kB
Formato Adobe PDF
982.98 kB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/1624130
Citazioni
  • ???jsp.display-item.citation.pmc??? 2
  • Scopus 4
  • ???jsp.display-item.citation.isi??? 3
social impact