Intranasal adenovirus-vectored vaccine for induction of long-lasting humoral immunity-mediated broad protection against influenza in mice

Eun Hye Kim, Hae Jung Park, Gye Yeong Han, Man Ki Song, Alexander Pereboev, Jeong S. Hong, Jun Chang, Young Ho Byun, Baik Lin Seong, Huan H. Nguyen

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Influenza vaccines aimed at inducing antibody (Ab) responses against viral surface hemagglutinin (HA) and neuraminidase (NA) provide sterile immunity to infection with the same subtypes. Vaccines targeting viral conserved determinants shared by the influenza A viruses (IAV) offer heterosubtypic immunity (HSI), a broad protection against different subtypes. We proposed that vaccines targeting both HA and the conserved ectodomain of matrix protein 2 (M2e) would provide protection against infection with the same subtype and also HSI against other subtypes. We report here that single intranasal immunization with a recombinant adenovirus (rAd) vector encoding both HA of H5 virus and M2e (rAdH5/M2e) induced significant HA- and M2especific Ab responses, along with protection against heterosubtypic challenge in mice. The protection is superior compared to that induced by rAd vector encoding either HA (rAdH5), or M2e (rAdM2e). While protection against homotypic H5 virus is primarily mediated by virus-neutralizing Abs, the cross-protection is associated with Abs directed to conserved stalk HA and M2e that seem to have an additive effect. Consistently, adoptive transfer of antisera induced by rAdH5/M2e provided the best protection against heterosubtypic challenge compared to that provided by antisera derived from mice immunized with rAdH5 or rAdM2e. These results support the development of rAd-vectored vaccines encoding both H5 and M2e as universal vaccines against different IAV subtypes.

Original languageEnglish
Pages (from-to)9693-9703
Number of pages11
JournalJournal of Virology
Volume88
Issue number17
DOIs
Publication statusPublished - 2014 Jan 1

Fingerprint

Adenovirus Vaccines
Hemagglutinins
Adenoviridae
hemagglutinins
Humoral Immunity
humoral immunity
influenza
Human Influenza
vaccines
Immunity
Influenza A virus
mice
Viruses
Antibody Formation
Immune Sera
Vaccines
Viral Hemagglutinins
immunity
Viral Vaccines
Cross Protection

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Kim, Eun Hye ; Park, Hae Jung ; Han, Gye Yeong ; Song, Man Ki ; Pereboev, Alexander ; Hong, Jeong S. ; Chang, Jun ; Byun, Young Ho ; Seong, Baik Lin ; Nguyen, Huan H. / Intranasal adenovirus-vectored vaccine for induction of long-lasting humoral immunity-mediated broad protection against influenza in mice. In: Journal of Virology. 2014 ; Vol. 88, No. 17. pp. 9693-9703.
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abstract = "Influenza vaccines aimed at inducing antibody (Ab) responses against viral surface hemagglutinin (HA) and neuraminidase (NA) provide sterile immunity to infection with the same subtypes. Vaccines targeting viral conserved determinants shared by the influenza A viruses (IAV) offer heterosubtypic immunity (HSI), a broad protection against different subtypes. We proposed that vaccines targeting both HA and the conserved ectodomain of matrix protein 2 (M2e) would provide protection against infection with the same subtype and also HSI against other subtypes. We report here that single intranasal immunization with a recombinant adenovirus (rAd) vector encoding both HA of H5 virus and M2e (rAdH5/M2e) induced significant HA- and M2especific Ab responses, along with protection against heterosubtypic challenge in mice. The protection is superior compared to that induced by rAd vector encoding either HA (rAdH5), or M2e (rAdM2e). While protection against homotypic H5 virus is primarily mediated by virus-neutralizing Abs, the cross-protection is associated with Abs directed to conserved stalk HA and M2e that seem to have an additive effect. Consistently, adoptive transfer of antisera induced by rAdH5/M2e provided the best protection against heterosubtypic challenge compared to that provided by antisera derived from mice immunized with rAdH5 or rAdM2e. These results support the development of rAd-vectored vaccines encoding both H5 and M2e as universal vaccines against different IAV subtypes.",
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Kim, EH, Park, HJ, Han, GY, Song, MK, Pereboev, A, Hong, JS, Chang, J, Byun, YH, Seong, BL & Nguyen, HH 2014, 'Intranasal adenovirus-vectored vaccine for induction of long-lasting humoral immunity-mediated broad protection against influenza in mice', Journal of Virology, vol. 88, no. 17, pp. 9693-9703. https://doi.org/10.1128/JVI.00823-14

Intranasal adenovirus-vectored vaccine for induction of long-lasting humoral immunity-mediated broad protection against influenza in mice. / Kim, Eun Hye; Park, Hae Jung; Han, Gye Yeong; Song, Man Ki; Pereboev, Alexander; Hong, Jeong S.; Chang, Jun; Byun, Young Ho; Seong, Baik Lin; Nguyen, Huan H.

In: Journal of Virology, Vol. 88, No. 17, 01.01.2014, p. 9693-9703.

Research output: Contribution to journalArticle

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AU - Kim, Eun Hye

AU - Park, Hae Jung

AU - Han, Gye Yeong

AU - Song, Man Ki

AU - Pereboev, Alexander

AU - Hong, Jeong S.

AU - Chang, Jun

AU - Byun, Young Ho

AU - Seong, Baik Lin

AU - Nguyen, Huan H.

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