RGD capsid modification enhances mucosal protective immunity of a non-human primate adenovirus vector expressing PseudomonasaeruginosaOprF

A. Krause, W. Z. Whu, J. Qiu, D. Wafadari, N. R. Hackett, A. Sharma, Ronald Crystal, S. Worgall

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Replication-deficient adenoviral (Ad) vectors of non-human serotypes can serve as Ad vaccine platforms to circumvent pre-existing anti-human Ad immunity. We found previously that, in addition to that feature, a non-human primate-based AdC7 vector expressing outer membrane protein F of P. aeruginosa (AdC7OprF) was more potent in inducing lung mucosal and protective immunity compared to a human Ad5-based vector. In this study we analysed if genetic modification of the AdC7 fibre to display an integrin-binding arginine-glycine-aspartic acid (RGD) sequence can further enhance lung mucosal immunogenicity of AdC7OprF. Intratracheal immunization of mice with either AdC7OprF.RGD or AdC7OprF induced robust serum levels of anti-OprF immunoglobulin (Ig)G up to 12 weeks that were higher compared to immunization with the human vectors Ad5OprF or Ad5OprF.RGD. OprF-specific cellular responses in lung T cells isolated from mice immunized with AdC7OprF.RGD and AdC7OprF were similar for T helper type 1 (Th1) [interferon (IFN)-γ in CD8+ and interleukin (IL)-12 in CD4+], Th2 (IL-4, IL-5 and IL-13 in CD4+) and Th17 (IL-17 in CD4+). Interestingly, AdC7OprF.RGD induced more robust protective immunity against pulmonary infection with P.aeruginosa compared to AdC7OprF or the control Ad5 vectors. The enhanced protective immunity induced by AdC7OprF.RGD was maintained in the absence of alveolar macrophages (AM) or CD1d natural killer T cells. Together, the data suggest that addition of RGD to the fibre of an AdC7-based vaccine is useful to enhance its mucosal protective immunogenicity.

Original languageEnglish
Pages (from-to)230-241
Number of pages12
JournalClinical and Experimental Immunology
Volume173
Issue number2
DOIs
Publication statusPublished - 1 Aug 2013
Externally publishedYes

Fingerprint

Mucosal Immunity
Capsid
Adenoviridae
Primates
Immunity
Lung
Immunization
Vaccines
Interferon Type I
Natural Killer T-Cells
Interleukin-13
Interleukin-17
Interleukin-5
Alveolar Macrophages
Interleukin-12
Aspartic Acid
Integrins
Glycine
Arginine
Immunoglobulin G

Keywords

  • adenovirus
  • lung
  • mucosal immunity
  • pseudomonas
  • RGD

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

RGD capsid modification enhances mucosal protective immunity of a non-human primate adenovirus vector expressing PseudomonasaeruginosaOprF. / Krause, A.; Whu, W. Z.; Qiu, J.; Wafadari, D.; Hackett, N. R.; Sharma, A.; Crystal, Ronald; Worgall, S.

In: Clinical and Experimental Immunology, Vol. 173, No. 2, 01.08.2013, p. 230-241.

Research output: Contribution to journalArticle

Krause, A. ; Whu, W. Z. ; Qiu, J. ; Wafadari, D. ; Hackett, N. R. ; Sharma, A. ; Crystal, Ronald ; Worgall, S. / RGD capsid modification enhances mucosal protective immunity of a non-human primate adenovirus vector expressing PseudomonasaeruginosaOprF. In: Clinical and Experimental Immunology. 2013 ; Vol. 173, No. 2. pp. 230-241.
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