Sublingual immunization with M2-based vaccine induces broad protective immunity against influenza

• Published in: PloS one 2011-11, Vol.6 (11), p.e27953-e27953
• Main Authors: Shim, Byoung-Shik, Choi, Young Ki, Yun, Cheol-Heui, Lee, Eu-Gene, Jeon, Yoon Seong, Park, Sung-Moo, Cheon, In Su, Joo, Dong-Hyun, Cho, Chung Hwan, Song, Min-Suk, Seo, Sang-Uk, Byun, Young-Ho, Park, Hae-Jung, Poo, Haryoung, Seong, Baik Lin, Kim, Jae Ouk, Nguyen, Huan Huu, Stadler, Konrad, Kim, Dong Wook, Hong, Kee-Jong, Czerkinsky, Cecil, Song, Man Ki
• Format: Article
• Language: English
• Subjects: Adjuvants; Administration, Intranasal; Administration, Sublingual; Agricultural biotechnology; Agriculture; Amino Acid Sequence; Amino acids; Analysis; Animal models; Animals; Antibodies; Antibody Formation - immunology; Antibody Specificity - immunology; Antigens; Avian flu; Biology; Biomedical materials; Cross Protection - immunology; Developing countries; Disease control; Drug delivery systems; E coli; Engineering schools; Epidemics; Epidemiology; Epithelium; Escherichia coli; Female; Health aspects; HeLa Cells; Humans; Immune response; Immunity; Immunity - immunology; Immunization; Immunoglobulins; Infections; Influenza; Influenza A; Influenza A Virus, H1N1 Subtype - immunology; Influenza vaccines; Influenza Vaccines - administration & dosage; Influenza Vaccines - immunology; Influenza viruses; Influenza, Human - immunology; Influenza, Human - prevention & control; Influenza, Human - virology; Laboratories; LDCs; Life sciences; Lung - immunology; Lung - virology; Lungs; Matrix protein; Medical research; Medicine; Mice; Mice, Inbred BALB C; Molecular Sequence Data; Mucosal immunity; Olfactory epithelium; Onchocerca volvulus; Orthomyxoviridae Infections - immunology; Orthomyxoviridae Infections - prevention & control; Orthomyxoviridae Infections - virology; Pandemics; Pharmacy; Plasmids - genetics; Proteins; Recombinant Proteins - immunology; Respiratory tract; Solubility; Vaccines; Viral Matrix Proteins - chemistry; Viral Matrix Proteins - immunology; Viral Matrix Proteins - isolation & purification; Viruses; Wildlife conservation
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0027953

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. 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. 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.