title: Mucosally administered Lactobacillus surface-displayed influenza antigens (sM2 and HA2) with cholera toxin subunit A1 (CTA1) Induce broadly protective immune responses against divergent influenza subtypes.
abstract: The development of a universal influenza vaccine that provides broad cross protection against existing and unforeseen influenza viruses is a critical challenge. In this study, we constructed and expressed conserved sM2 and HA2 influenza antigens with cholera toxin subunit A1 (CTA1) on the surface of Lactobacillus casei (pgsA-CTA1sM2HA2/L. casei). Oral and nasal administrations of recombinant L. casei into mice resulted in high levels of serum immunoglobulin G (IgG) and their isotypes (IgG1 & IgG2a) as well as mucosal IgA. The mucosal administration of pgsA-CTA1sM2HA2/L. casei may also significantly increase the levels of sM2- or HA2-specific cell-mediated immunity because increased release of both IFN-γ and IL-4 was observed. The recombinant pgsA-CTA1sM2HA2/L. casei provided better protection of BALB/c mice against 10 times the 50% mouse lethal doses (MLD50) of homologous A/EM/Korea/W149/06(H5N1) or A/Aquatic bird/Korea/W81/2005 (H5N2) and heterologous A/Puerto Rico/8/34(H1N1), or A/Chicken/Korea/116/2004(H9N2) or A/Philippines/2/08(H3N2) viruses, compared with L. casei harboring sM2HA2 and also the protection was maintained up to seven months after administration. These results indicate that recombinant L. casei expressing the highly conserved sM2, HA2 of influenza and CTA1 as a mucosal adjuvant could be a potential mucosal vaccine candidate or tool to protect against divergent influenza viruses for human and animal.
authors.affiliation: College of Veterinary Medicine (BK21 Plus Program), Chungnam National University, Daejeon, Republic of Korea.
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.affiliation: College of Veterinary Medicine (BK21 Plus Program), Chungnam National University, Daejeon, Republic of Korea; Faculty of Veterinary Medicine, Chittagong Veterinary and Animal Sciences University, Chittagong 4202, Bangladesh.
authors.forename: Mohammed Y E
authors.initials: MY
authors.lastname: Chowdhury
authors.affiliation: College of Veterinary Medicine (BK21 Plus Program), Chungnam National University, Daejeon, Republic of Korea.
authors.forename: Jae-Hoon
authors.initials: JH
authors.lastname: Kim
authors.affiliation: College of Veterinary Medicine (BK21 Plus Program), Chungnam National University, Daejeon, Republic of Korea.
authors.forename: Tae-Hwan
authors.initials: TH
authors.lastname: Kim
authors.affiliation: College of Veterinary Medicine (BK21 Plus Program), Chungnam National University, Daejeon, Republic of Korea.
authors.forename: Prabuddha
authors.initials: P
authors.lastname: Pathinayake
authors.affiliation: College of Veterinary Medicine (BK21 Plus Program), Chungnam National University, Daejeon, Republic of Korea.
authors.forename: Wan-Seo
authors.initials: WS
authors.lastname: Koo
authors.affiliation: Foot and Mouth Disease Division, Animal Quarantine and Inspection Agency, Anyang, Republic of Korea.
authors.forename: Min-Eun
authors.initials: ME
authors.lastname: Park
authors.affiliation: Foot and Mouth Disease Division, Animal Quarantine and Inspection Agency, Anyang, Republic of Korea.
authors.forename: Ji-Eun
authors.initials: JE
authors.lastname: Yoon
authors.affiliation: BioLeaders Corporation, Daejeon, Republic of Korea.
authors.forename: Jong-Bok
authors.initials: JB
authors.lastname: Roh
authors.affiliation: BioLeaders Corporation, Daejeon, Republic of Korea.
authors.forename: Seung-Pyo
authors.initials: SP
authors.lastname: Hong
authors.affiliation: BioLeaders Corporation, Daejeon, Republic of Korea.
authors.forename: Moon-Hee
authors.initials: MH
authors.lastname: Sung
authors.affiliation: College of Veterinary Medicine (BK21 Plus Program), Chungnam National University, Daejeon, Republic of Korea. Electronic address: jongsool@cnu.ac.kr.
authors.forename: Jong-Soo
authors.initials: JS
authors.lastname: Lee
authors.affiliation: College of Veterinary Medicine (BK21 Plus Program), Chungnam National University, Daejeon, Republic of Korea. Electronic address: cjkim@cnu.ac.kr.
authors.forename: Chul-Joong
authors.initials: CJ
authors.lastname: Kim
mesh_terms: D000276:Adjuvants, Immunologic; D000281:Administration, Intranasal; D000818:Animals; D000954:Antigens, Surface / Q000276:immunology; D002772:Cholera Toxin / Q000276:immunology; D056738:Cross Protection / Q000276:immunology*; D004353:Drug Evaluation, Preclinical; D007111:Immunity, Cellular / Q000276:immunology*; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology; D053125:Influenza A Virus, H5N2 Subtype / Q000276:immunology; D053127:Influenza A Virus, H9N2 Subtype / Q000276:immunology; D009980:Influenza A virus / Q000235:genetics* / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D015847:Interleukin-4 / Q000276:immunology; D007778:Lactobacillus / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000517:prevention & control*; D056910:Republic of Korea
chemical_list: D000276:Adjuvants, Immunologic; D000954:Antigens, Surface; D007252:Influenza Vaccines; D015847:Interleukin-4; D002772:Cholera Toxin
keywords: Influenza; Mucosal immunity; surface display