Mucosal DNA vaccine immunization against measles with a highly attenuated Shigella flexneri vector

Glenn Fennelly, Shibber A. Khan, Maria A. Abadi, T. Fabian Wild, Barry R. Bloom

Research output: Contribution to journalArticle

104 Citations (Scopus)

Abstract

An intranasal vaccine vector would elicit protective immunity at the respiratory mucosa, the portal of entry and the primary site for replication for measles virus (MV) and other respiratory viruses. In a murine model of pulmonary Shigella, we demonstrate here that a candidate-attenuated Shigella vaccine vector is safely tolerated in IFN-γ deficient mice at an inoculum that is 1 million-fold higher than the inoculum of the wild-type parent strain that would be lethal for greater than 90% of these mice. Also, following intranasal inoculation, the Δasd Shigella harboring a DNA MV vaccine plasmid induces a vigorous MV-specific Th1-type (both CD8 + CTL and IFN-γ) and, to a lesser degree, Th2-type responses among splenocytes in addition to low levels of IgG and IgA in the serum. Priming for MV-specific CTL responses was possible in mice that had prior infection with a wild-type Shigella of the same serotype. Remarkably, mice immunized by the intranasal route with attenuated Shigella harboring the DNA MV vaccine plasmid had a level of MV-specific CTL activity among splenocytes that was comparable with levels observed in mice immunized by the i.p. route with attenuated Salmonella typhi harboring the same DNA vaccine plasmid, despite the fact that Shigella remained localized to the lungs, yet Salmonella disseminated to the spleen following inoculation. Thus, Δasd Shigella represents a very useful vector for delivery of DNA vaccines to mucosal lymphoid tissues.

Original languageEnglish (US)
Pages (from-to)1603-1610
Number of pages8
JournalJournal of Immunology
Volume162
Issue number3
StatePublished - Feb 1 1999
Externally publishedYes

Fingerprint

Shigella flexneri
Measles virus
DNA Vaccines
Shigella
Measles
Immunization
Measles Vaccine
Plasmids
DNA Viruses
Shigella Vaccines
Respiratory Mucosa
Lung
Attenuated Vaccines
Salmonella typhi
Lymphoid Tissue
Salmonella
Immunoglobulin A
Immunity
Mucous Membrane
Vaccines

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Fennelly, G., Khan, S. A., Abadi, M. A., Fabian Wild, T., & Bloom, B. R. (1999). Mucosal DNA vaccine immunization against measles with a highly attenuated Shigella flexneri vector. Journal of Immunology, 162(3), 1603-1610.
Fennelly, Glenn ; Khan, Shibber A. ; Abadi, Maria A. ; Fabian Wild, T. ; Bloom, Barry R. / Mucosal DNA vaccine immunization against measles with a highly attenuated Shigella flexneri vector. In: Journal of Immunology. 1999 ; Vol. 162, No. 3. pp. 1603-1610.
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Fennelly, G, Khan, SA, Abadi, MA, Fabian Wild, T & Bloom, BR 1999, 'Mucosal DNA vaccine immunization against measles with a highly attenuated Shigella flexneri vector', Journal of Immunology, vol. 162, no. 3, pp. 1603-1610.

Mucosal DNA vaccine immunization against measles with a highly attenuated Shigella flexneri vector. / Fennelly, Glenn; Khan, Shibber A.; Abadi, Maria A.; Fabian Wild, T.; Bloom, Barry R.

In: Journal of Immunology, Vol. 162, No. 3, 01.02.1999, p. 1603-1610.

Research output: Contribution to journalArticle

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