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Targeted prokaryotic delivery of a conserved influenza A virus epitope for oral vaccination

Lei Deng (UGent)
(2015)
Author
Promoter
(UGent)
Organization
Abstract
Influenza virus infection is a vaccine preventable disease. Marketed influenza vaccines eliciting anti-hemagglutinin antibody based efficient neutralizing protection against antigenically matching influenza viruses. The drawbacks of conventional influenza vaccines for human use is their narrow specificity: the vaccines offer little protection against antigenically drifted strains of the same subtype and are futile in preventing disease following infection with a distinct serotype of influenza A virus. The highly conserved ectodomain of matrix protein 2 (M2e) is a promising epitope to induce cross-protection immunity. We used filamentous fd enterobacteriophages to display M2e amino acids 2–16 at the N-terminus of pVIII, the major coat protein of fd phage. It is showed that the recombinant f88−M2e2-16 phages are replication competent and incorporated M2e2-16-pVIII in the proportion of around 5%. The mice immunized with purified f88−M2e2-16 phages in the presence of incomplete Freund’s adjuvant, induced robust M2e-specific serum IgG and were protected from lethal dose challenge with H1N1 or H3N2 viruses. Then we aimed to develop an oral vaccine based on a live bacterial targeting vector combined with antigen-displaying bacteriophage. Escherichia coli cells expressing invasin from Yersinia pseudotuberculosis were internalized by mammalian HEp-2 cells and specifically adhered to mouse intestinal microfold (M) cells ex vivo. Invasin-expressing E.coli cells remained permissive for f88M2e2-16 and f88 control phages and became persistently infected. To evaluate the immunogenic and protective efficacy of the invasive E.coli-phage combination, the eight-week-old Balb/c mice were intragastrically administered with E.coli co-expressing invasin and f88M2e2-16 by gavage. Vaccination induced M2e-specific serum IgG antibodies and provided slight and statistically significant protection against intranasal infection with H3N2 influenza virus compared to the control treated mice groups. These results showed a prove-of-concept that a vaccine antigen that is displayed by fd phage can be delivered orally as a live vaccine comprising the Peyer’s patches-targeting bacterial host.
Keywords
invasin, influenza A virus, phage, oral vaccines

Citation

Please use this url to cite or link to this publication:

MLA
Deng, Lei. “Targeted Prokaryotic Delivery of a Conserved Influenza A Virus Epitope for Oral Vaccination.” 2015 : n. pag. Print.
APA
Deng, L. (2015). Targeted prokaryotic delivery of a conserved influenza A virus epitope for oral vaccination. Ghent University. Faculty of Sciences, Ghent, Belgium.
Chicago author-date
Deng, Lei. 2015. “Targeted Prokaryotic Delivery of a Conserved Influenza A Virus Epitope for Oral Vaccination”. Ghent, Belgium: Ghent University. Faculty of Sciences.
Chicago author-date (all authors)
Deng, Lei. 2015. “Targeted Prokaryotic Delivery of a Conserved Influenza A Virus Epitope for Oral Vaccination”. Ghent, Belgium: Ghent University. Faculty of Sciences.
Vancouver
1.
Deng L. Targeted prokaryotic delivery of a conserved influenza A virus epitope for oral vaccination. [Ghent, Belgium]: Ghent University. Faculty of Sciences; 2015.
IEEE
[1]
L. Deng, “Targeted prokaryotic delivery of a conserved influenza A virus epitope for oral vaccination,” Ghent University. Faculty of Sciences, Ghent, Belgium, 2015.
@phdthesis{6988424,
  abstract     = {Influenza virus infection is a vaccine preventable disease. Marketed influenza vaccines eliciting anti-hemagglutinin antibody based efficient neutralizing protection against antigenically matching influenza viruses. The drawbacks of conventional influenza vaccines for human use is their narrow specificity: the vaccines offer little protection against antigenically drifted strains of the same subtype and are futile in preventing disease following infection with a distinct serotype of influenza A virus. The highly conserved ectodomain of matrix protein 2 (M2e) is a promising epitope to induce cross-protection immunity. We used filamentous fd enterobacteriophages to display M2e amino acids 2–16 at the N-terminus of pVIII, the major coat protein of fd phage. It is showed that the recombinant f88−M2e2-16 phages are replication competent and incorporated M2e2-16-pVIII in the proportion of around 5%. The mice immunized with purified f88−M2e2-16 phages in the presence of incomplete Freund’s adjuvant, induced robust M2e-specific serum IgG and were protected from lethal dose challenge with H1N1 or H3N2 viruses. Then we aimed to develop an oral vaccine based on a live bacterial targeting vector combined with antigen-displaying bacteriophage. Escherichia coli cells expressing invasin from Yersinia pseudotuberculosis were internalized by mammalian HEp-2 cells and specifically adhered to mouse intestinal microfold (M) cells ex vivo. Invasin-expressing E.coli cells remained permissive for f88M2e2-16 and f88 control phages and became persistently infected. To evaluate the immunogenic and protective efficacy of the invasive E.coli-phage combination, the eight-week-old Balb/c mice were intragastrically administered with E.coli co-expressing invasin and f88M2e2-16 by gavage. Vaccination induced M2e-specific serum IgG antibodies and provided slight and statistically significant protection against intranasal infection with H3N2 influenza virus compared to the control treated mice groups. These results showed a prove-of-concept that a vaccine antigen that is displayed by fd phage can be delivered orally as a live vaccine comprising the Peyer’s patches-targeting bacterial host.},
  author       = {Deng, Lei},
  keywords     = {invasin,influenza A virus,phage,oral vaccines},
  language     = {eng},
  pages        = {182},
  publisher    = {Ghent University. Faculty of Sciences},
  school       = {Ghent University},
  title        = {Targeted prokaryotic delivery of a conserved influenza A virus epitope for oral vaccination},
  year         = {2015},
}