Sublingual immunization with M2-based vaccine induces broad protective immunity against influenza.
<h4>Background</h4>The ectodomain of matrix protein 2 (M2e) of influenza A virus is a rationale target antigen candidate for the development of a universal vaccine against influenza as M2e undergoes little sequence variation amongst human influenza A strains. Vaccine-induced M2e-specific...
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oai:doaj.org-article:672b846a88ac4c83937f716af3e0d5df2021-11-18T07:33:22ZSublingual immunization with M2-based vaccine induces broad protective immunity against influenza.1932-620310.1371/journal.pone.0027953https://doaj.org/article/672b846a88ac4c83937f716af3e0d5df2011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22140491/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>The ectodomain of matrix protein 2 (M2e) of influenza A virus is a rationale target antigen candidate for the development of a universal vaccine against influenza as M2e undergoes little sequence variation amongst human influenza A strains. Vaccine-induced M2e-specific antibodies (Abs) have been shown to display significant cross-protective activity in animal models. M2e-based vaccine constructs have been shown to be more protective when administered by the intranasal (i.n.) route than after parenteral injection. However, i.n. administration of vaccines poses rare but serious safety issues associated with retrograde passage of inhaled antigens and adjuvants through the olfactory epithelium. In this study, we examined whether the sublingual (s.l.) route could serve as a safe and effective alternative mucosal delivery route for administering a prototype M2e-based vaccine. The mechanism whereby s.l. immunization with M2e vaccine candidate induces broad protection against infection with different influenza virus subtypes was explored.<h4>Methods and results</h4>A recombinant M2 protein with three tandem copies of the M2e (3M2eC) was expressed in Escherichia coli. Parenteral immunizations of mice with 3M2eC induced high levels of M2e-specific serum Abs but failed to provide complete protection against lethal challenge with influenza virus. In contrast, s.l. immunization with 3M2eC was superior for inducing protection in mice. In the latter animals, protection was associated with specific Ab responses in the lungs.<h4>Conclusions</h4>The results demonstrate that s.l. immunization with 3M2eC vaccine induced airway mucosal immune responses along with broad cross-protective immunity to influenza. These findings may contribute to the understanding of the M2-based vaccine approach to control epidemic and pandemic influenza infections.Byoung-Shik ShimYoung Ki ChoiCheol-Heui YunEu-Gene LeeYoon Seong JeonSung-Moo ParkIn Su CheonDong-Hyun JooChung Hwan ChoMin-Suk SongSang-Uk SeoYoung-Ho ByunHae-Jung ParkHaryoung PooBaik Lin SeongJae Ouk KimHuan Huu NguyenKonrad StadlerDong Wook KimKee-Jong HongCecil CzerkinskyMan Ki SongPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 11, p e27953 (2011) |
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Medicine R Science Q Byoung-Shik Shim Young Ki Choi Cheol-Heui Yun Eu-Gene Lee Yoon Seong Jeon Sung-Moo Park In Su Cheon Dong-Hyun Joo Chung Hwan Cho Min-Suk Song Sang-Uk Seo Young-Ho Byun Hae-Jung Park Haryoung Poo Baik Lin Seong Jae Ouk Kim Huan Huu Nguyen Konrad Stadler Dong Wook Kim Kee-Jong Hong Cecil Czerkinsky Man Ki Song Sublingual immunization with M2-based vaccine induces broad protective immunity against influenza. |
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<h4>Background</h4>The ectodomain of matrix protein 2 (M2e) of influenza A virus is a rationale target antigen candidate for the development of a universal vaccine against influenza as M2e undergoes little sequence variation amongst human influenza A strains. Vaccine-induced M2e-specific antibodies (Abs) have been shown to display significant cross-protective activity in animal models. M2e-based vaccine constructs have been shown to be more protective when administered by the intranasal (i.n.) route than after parenteral injection. However, i.n. administration of vaccines poses rare but serious safety issues associated with retrograde passage of inhaled antigens and adjuvants through the olfactory epithelium. In this study, we examined whether the sublingual (s.l.) route could serve as a safe and effective alternative mucosal delivery route for administering a prototype M2e-based vaccine. The mechanism whereby s.l. immunization with M2e vaccine candidate induces broad protection against infection with different influenza virus subtypes was explored.<h4>Methods and results</h4>A recombinant M2 protein with three tandem copies of the M2e (3M2eC) was expressed in Escherichia coli. Parenteral immunizations of mice with 3M2eC induced high levels of M2e-specific serum Abs but failed to provide complete protection against lethal challenge with influenza virus. In contrast, s.l. immunization with 3M2eC was superior for inducing protection in mice. In the latter animals, protection was associated with specific Ab responses in the lungs.<h4>Conclusions</h4>The results demonstrate that s.l. immunization with 3M2eC vaccine induced airway mucosal immune responses along with broad cross-protective immunity to influenza. These findings may contribute to the understanding of the M2-based vaccine approach to control epidemic and pandemic influenza infections. |
format |
article |
author |
Byoung-Shik Shim Young Ki Choi Cheol-Heui Yun Eu-Gene Lee Yoon Seong Jeon Sung-Moo Park In Su Cheon Dong-Hyun Joo Chung Hwan Cho Min-Suk Song Sang-Uk Seo Young-Ho Byun Hae-Jung Park Haryoung Poo Baik Lin Seong Jae Ouk Kim Huan Huu Nguyen Konrad Stadler Dong Wook Kim Kee-Jong Hong Cecil Czerkinsky Man Ki Song |
author_facet |
Byoung-Shik Shim Young Ki Choi Cheol-Heui Yun Eu-Gene Lee Yoon Seong Jeon Sung-Moo Park In Su Cheon Dong-Hyun Joo Chung Hwan Cho Min-Suk Song Sang-Uk Seo Young-Ho Byun Hae-Jung Park Haryoung Poo Baik Lin Seong Jae Ouk Kim Huan Huu Nguyen Konrad Stadler Dong Wook Kim Kee-Jong Hong Cecil Czerkinsky Man Ki Song |
author_sort |
Byoung-Shik Shim |
title |
Sublingual immunization with M2-based vaccine induces broad protective immunity against influenza. |
title_short |
Sublingual immunization with M2-based vaccine induces broad protective immunity against influenza. |
title_full |
Sublingual immunization with M2-based vaccine induces broad protective immunity against influenza. |
title_fullStr |
Sublingual immunization with M2-based vaccine induces broad protective immunity against influenza. |
title_full_unstemmed |
Sublingual immunization with M2-based vaccine induces broad protective immunity against influenza. |
title_sort |
sublingual immunization with m2-based vaccine induces broad protective immunity against influenza. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2011 |
url |
https://doaj.org/article/672b846a88ac4c83937f716af3e0d5df |
work_keys_str_mv |
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