Mucosal vaccination with recombinant Lactobacillus casei-displayed CTA1-conjugated consensus matrix protein-2 (sM2) induces broad protection against divergent influenza subtypes in BALB/c mice.
To develop a safe and effective mucosal vaccine against pathogenic influenza viruses, we constructed recombinant Lactobacillus casei strains that express conserved matrix protein 2 with (pgsA-CTA1-sM2/L. casei) or without (pgsA-sM2/L. casei) cholera toxin subunit A1 (CTA1) on the surface. The surface localization of the fusion protein was verified by cellular fractionation analyses, flow cytometry and immunofluorescence microscopy. Oral and nasal inoculations of recombinant L. casei into mice resulted in high levels of serum immunoglobulin G (IgG) and mucosal IgA. However, the conjugation of cholera toxin subunit A1 induced more potent mucosal, humoral and cell-mediated immune responses. In a challenge test with 10 MLD50 of A/EM/Korea/W149/06(H5N1), A/Puerto Rico/8/34(H1N1), A/Aquatic bird /Korea/W81/2005(H5N2), A/Aquatic bird/Korea/W44/2005(H7N3), and A/Chicken/Korea/116/2004(H9N2) viruses, the recombinant pgsA-CTA1-sM2/L. casei provided better protection against lethal challenges than pgsA-sM2/L. casei, pgsA/L. casei and PBS in mice. These results indicate that mucosal immunization with recombinant L. casei expressing CTA1-conjugated sM2 protein on its surface is an effective means of eliciting protective immune responses against diverse influenza subtypes.
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, Bangladesh.
Mohammed Y E
MY
Chowdhury
College of Veterinary Medicine (BK21 Plus Program), Chungnam National University, Daejeon, Republic of Korea.
Rui
R
Li
College of Veterinary Medicine (BK21 Plus Program), Chungnam National University, Daejeon, Republic of Korea.
Jae-Hoon
JH
Kim
College of Veterinary Medicine (BK21 Plus Program), Chungnam National University, Daejeon, Republic of Korea.
Min-Eun
ME
Park
College of Veterinary Medicine (BK21 Plus Program), Chungnam National University, Daejeon, Republic of Korea.
Tae-Hwan
TH
Kim
College of Veterinary Medicine (BK21 Plus Program), Chungnam National University, Daejeon, Republic of Korea.
Prabuddha
P
Pathinayake
College of Veterinary Medicine (BK21 Plus Program), Chungnam National University, Daejeon, Republic of Korea.
Prasanna
P
Weeratunga
Laboratory Science Division, International Vaccine Institute, Seoul, Republic of Korea.
Man Ki
MK
Song
College of Veterinary Medicine (BK21 Plus Program), Chungnam National University, Daejeon, Republic of Korea.
Hwa-Young
HY
Son
BioLeaders Corporation, Daejeon, Republic of Korea.
Seung-Pyo
SP
Hong
BioLeaders Corporation, Daejeon, Republic of Korea.
Moon-Hee
MH
Sung
College of Veterinary Medicine (BK21 Plus Program), Chungnam National University, Daejeon, Republic of Korea.
Jong-Soo
JS
Lee
College of Veterinary Medicine (BK21 Plus Program), Chungnam National University, Daejeon, Republic of Korea.
Chul-Joong
CJ
Kim
D000818:Animals; D005260:Female; D009980:Influenza A virus / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D007780:Lacticaseibacillus casei / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control*; D014611:Vaccination / Q000379:methods*
D007252:Influenza Vaccines