A paramyxovirus-vectored intranasal vaccine against Ebola virus is immunogenic in vector-immune animals

Lijuan Yang, Anthony Sanchez, Jerrold M. Ward, Brian R. Murphy, Peter L. Collins, Alexander Bukreyev

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Ebola virus (EBOV) causes outbreaks of a highly lethal hemorrhagic fever in humans. The virus can be transmitted by direct contact as well as by aerosol and is considered a potential bioweapon. Because direct immunization of the respiratory tract should be particularly effective against infection of mucosal surfaces, we previously developed an intranasal vaccine based on replication-competent human parainfluenza virus type 3 (HPIV3) expressing EBOV glycoprotein GP (HPIV3/EboGP) and showed that it is immunogenic and protective against a high dose parenteral EBOV challenge. However, because the adult human population has considerable immunity to HPIV3, which is a common human pathogen, replication and immunogenicity of the vaccine in this population might be greatly restricted. Indeed, in the present study, replication of the vaccine in the respiratory tract of HPIV3-immune guinea pigs was found to be restricted to undetectable levels. This restriction appeared to be based on both neutralizing antibodies and cellular or other components of the immunity to HPIV3. Surprisingly, even though replication of HPIV3/EboGP was highly restricted in HPIV3-immune animals, it induced a high level of EBOV-specific antibodies that nearly equaled that obtained in HPIV3-naive animals. We also show that the previously demonstrated presence of functional GP in the vector particle was not associated with increased replication in the respiratory tract nor with spread beyond the respiratory tract of HPIV3-naive guinea pigs, indicating that expression and functional incorporation of the attachment/penetration glycoprotein of this systemic virus did not mediate a change in tissue tropism.

Original languageEnglish
Pages (from-to)255-264
Number of pages10
JournalVirology
Volume377
Issue number2
DOIs
StatePublished - Aug 1 2008
Externally publishedYes

Fingerprint

Ebola Vaccines
Human parainfluenza virus 3
Ebolavirus
Respiratory System
Immunity
Glycoproteins
Guinea Pigs
Vaccines

Keywords

  • Antibody
  • Ebola
  • Immunization
  • Immunogenicity
  • Respiratory
  • Vaccine
  • Virus

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

Cite this

A paramyxovirus-vectored intranasal vaccine against Ebola virus is immunogenic in vector-immune animals. / Yang, Lijuan; Sanchez, Anthony; Ward, Jerrold M.; Murphy, Brian R.; Collins, Peter L.; Bukreyev, Alexander.

In: Virology, Vol. 377, No. 2, 01.08.2008, p. 255-264.

Research output: Contribution to journalArticle

Yang, Lijuan ; Sanchez, Anthony ; Ward, Jerrold M. ; Murphy, Brian R. ; Collins, Peter L. ; Bukreyev, Alexander. / A paramyxovirus-vectored intranasal vaccine against Ebola virus is immunogenic in vector-immune animals. In: Virology. 2008 ; Vol. 377, No. 2. pp. 255-264.
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