Intranasal administration of a flagellin-adjuvanted inactivated influenza vaccine enhances mucosal immune responses to protect mice against lethal infection

Seol Hee Hong, Young Ho Byun, Chung Truong Nguyen, Soo Young Kim, Baik Lin Seong, Songyong Park, Gyu Jin Woo, Yeup Yoon, Jeong Tae Koh, Kohtaro Fujihashi, Joon Haeng Rhee, Shee Eun Lee

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

The influenza virus, a mucosal pathogen that infects the respiratory tract, is a major global health issue. There have been attempts to mucosally administer inactivated influenza vaccines to induce both mucosal and systemic immune responses. However, mucosally administered inactivated influenza vaccine has low immunogenicity, which is partially due to the lack of an effective mucosal adjuvant. The development of a safe and effective mucosal adjuvant is a prerequisite to the practical use of a mucosal inactivated influenza vaccine. We have previously demonstrated that a bacterial flagellin, Vibrio vulnificus FlaB, when mixed with antigen and administered intranasally, exerts a strong mucosal adjuvant activity by stimulating the Toll-like receptor 5 (TLR5). In this study, we tested whether the FlaB protein could serve as an effective mucosal adjuvant for an inactivated trivalent influenza vaccine (TIV) manufactured for humans; in a murine vaccination model, this vaccine consists of A/Brisbane/59/07 (H1N1 subtype), A/Uruguay/716/07 (H3N2 subtype), and B/Florida/4/06 (B type). Intranasal co-administration of the TIV with FlaB induced prominent humoral responses as demonstrated by high influenza-specific IgA levels in both the mucosal secretions and serum and significant specific IgG induction in the systemic compartment. The FlaB protein significantly potentiated influenza-specific cytokine production by draining lymph node cells and splenocytes. The FlaB mucosal adjuvant conferred excellent protection against a lethal challenge with a live virulent virus with high hemagglutination inhibition (HAI) antibody (Ab) titers. The FlaB did not accumulate in the olfactory nerve and epithelium, guaranteeing against a retrograde uptake into the central nervous system. These results suggest that FlaB can be used as a promising mucosal adjuvant for nasal inactivated influenza vaccine development.

Original languageEnglish
Pages (from-to)466-474
Number of pages9
JournalVaccine
Volume30
Issue number2
DOIs
Publication statusPublished - 2012 Jan 5

Fingerprint

intranasal administration
Flagellin
mucosal immunity
Intranasal Administration
flagellin
Mucosal Immunity
Inactivated Vaccines
Influenza Vaccines
influenza
vaccines
adjuvants
mice
Infection
infection
Human Influenza
Toll-Like Receptor 5
Vibrio vulnificus
Olfactory Nerve
Uruguay
Olfactory Mucosa

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Immunology and Microbiology(all)
  • veterinary(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

Cite this

Hong, Seol Hee ; Byun, Young Ho ; Nguyen, Chung Truong ; Kim, Soo Young ; Seong, Baik Lin ; Park, Songyong ; Woo, Gyu Jin ; Yoon, Yeup ; Koh, Jeong Tae ; Fujihashi, Kohtaro ; Rhee, Joon Haeng ; Lee, Shee Eun. / Intranasal administration of a flagellin-adjuvanted inactivated influenza vaccine enhances mucosal immune responses to protect mice against lethal infection. In: Vaccine. 2012 ; Vol. 30, No. 2. pp. 466-474.
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abstract = "The influenza virus, a mucosal pathogen that infects the respiratory tract, is a major global health issue. There have been attempts to mucosally administer inactivated influenza vaccines to induce both mucosal and systemic immune responses. However, mucosally administered inactivated influenza vaccine has low immunogenicity, which is partially due to the lack of an effective mucosal adjuvant. The development of a safe and effective mucosal adjuvant is a prerequisite to the practical use of a mucosal inactivated influenza vaccine. We have previously demonstrated that a bacterial flagellin, Vibrio vulnificus FlaB, when mixed with antigen and administered intranasally, exerts a strong mucosal adjuvant activity by stimulating the Toll-like receptor 5 (TLR5). In this study, we tested whether the FlaB protein could serve as an effective mucosal adjuvant for an inactivated trivalent influenza vaccine (TIV) manufactured for humans; in a murine vaccination model, this vaccine consists of A/Brisbane/59/07 (H1N1 subtype), A/Uruguay/716/07 (H3N2 subtype), and B/Florida/4/06 (B type). Intranasal co-administration of the TIV with FlaB induced prominent humoral responses as demonstrated by high influenza-specific IgA levels in both the mucosal secretions and serum and significant specific IgG induction in the systemic compartment. The FlaB protein significantly potentiated influenza-specific cytokine production by draining lymph node cells and splenocytes. The FlaB mucosal adjuvant conferred excellent protection against a lethal challenge with a live virulent virus with high hemagglutination inhibition (HAI) antibody (Ab) titers. The FlaB did not accumulate in the olfactory nerve and epithelium, guaranteeing against a retrograde uptake into the central nervous system. These results suggest that FlaB can be used as a promising mucosal adjuvant for nasal inactivated influenza vaccine development.",
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Hong, SH, Byun, YH, Nguyen, CT, Kim, SY, Seong, BL, Park, S, Woo, GJ, Yoon, Y, Koh, JT, Fujihashi, K, Rhee, JH & Lee, SE 2012, 'Intranasal administration of a flagellin-adjuvanted inactivated influenza vaccine enhances mucosal immune responses to protect mice against lethal infection', Vaccine, vol. 30, no. 2, pp. 466-474. https://doi.org/10.1016/j.vaccine.2011.10.058

Intranasal administration of a flagellin-adjuvanted inactivated influenza vaccine enhances mucosal immune responses to protect mice against lethal infection. / Hong, Seol Hee; Byun, Young Ho; Nguyen, Chung Truong; Kim, Soo Young; Seong, Baik Lin; Park, Songyong; Woo, Gyu Jin; Yoon, Yeup; Koh, Jeong Tae; Fujihashi, Kohtaro; Rhee, Joon Haeng; Lee, Shee Eun.

In: Vaccine, Vol. 30, No. 2, 05.01.2012, p. 466-474.

Research output: Contribution to journalArticle

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AU - Hong, Seol Hee

AU - Byun, Young Ho

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AU - Kim, Soo Young

AU - Seong, Baik Lin

AU - Park, Songyong

AU - Woo, Gyu Jin

AU - Yoon, Yeup

AU - Koh, Jeong Tae

AU - Fujihashi, Kohtaro

AU - Rhee, Joon Haeng

AU - Lee, Shee Eun

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