Sublingual Administration of Bacteria-Expressed Influenza Virus Hemagglutinin 1 (HA1) Induces Protection against Infection with 2009 Pandemic H1N1 Influenza Virus

다국어 초록 (Multilingual Abstract)

Influenza viruses are respiratory pathogens that continue to pose a significantly high risk of morbidity and mortality of humans worldwide. Vaccination is one of the most effective strategies for minimizing damages by influenza outbreaks. In addition, rapid development and production of efficient vaccine with convenient administration is required in case of influenza pandemic. In this study, we generated recombinant influenza virus hemagglutinin protein 1 (sHA1) of 2009 pandemic influenza virus as a vaccine candidate using a wellestablished bacterial expression system and administered it into mice via sublingual (s.l.) route. We found that s.l. immunization with the recombinant sHA1 plus cholera toxin (CT) induced mucosal antibodies as well as systemic antibodies including neutralizing Abs and provided complete protection against infection with pandemic influenza virus A/CA/04/09 (H1N1) in mice. Indeed, the protection efficacy was comparable with that induced by intramuscular (i.m.) immunization route utilized as general administration route of influenza vaccine. These results suggest that s.l. vaccination with the recombinant non-glycosylated HA1 protein offers an alternative strategy to control influenza outbreaks including pandemics.

참고문헌 (Reference)

1 Berhanu, A., "Vaccination of balb/c mice with Escherichia coli-expressed vaccinia virus proteins A27L, B5R, and D8L protects mice from lethal vaccinia virus challenge" 82 : 3517-3529, 2008

2 Hebert, D. N., "The number and location of glycans on influenza hemagglutinin determine folding and association with calnexin and calreticulin" 139 : 613-623, 1997

3 Reisinger, K. S., "Subunit influenza vaccines produced from cell culture or in embryonated chicken eggs: Comparison of safety, reactogenicity, and immunogenicity" 200 : 849-857, 2009

4 Song, J.H., "Sublingual vaccination with influenza virus protects mice against lethal viral infection" 105 : 1644-1649, 2008

5 Cuburu, N., "Sublingual immunization induces broad-based systemic and mucosal immune responses in mice" 25 : 8598-8610, 2007

6 Stevens, J., "Structure of the uncleaved human H1 hemagglutinin from the extinct 1918 influenza virus" 303 : 1866-1870, 2004

7 Khan, K., "Spread of a novel influenza a (H1N1) virus via global airline transportation" 361 : 212-214, 2009

8 Shih, A. C. C., "Simultaneous amino acid substitutions at antigenic sites drive influenza a hemagglutinin evolution" 6283-, 2007

9 Agostinis, F., "Safety of sublingual immunotherapy with a monomeric allergoid in very young children" 60 : 133-, 2005

10 Skehel, J.J., "Receptor binding and membrane fusion in virus entry: The influenza hemagglutinin" 69 : 531-569, 2000

11 Ahmed, R., "Protective immunity and susceptibility to infectious diseases: Lessons from the 1918 influenza pandemic" 8 : 1188-1193, 2007

12 Armstrong, M. E., "Proinflammatory responses in the murine brain after intranasal delivery of cholera toxin: Implications for the use of ab toxins as adjuvants in intranasal vaccines" 192 : 1628-1633, 2005

13 Igarashi, M., "Predicting the antigenic structure of the pandemic (H1N1) 2009 influenza virus hemagglutinin" 5 : 8553-, 2010

14 Kim, J. K., "Pathogenicity and vaccine efficacy of different clades of Asian H5N1 avian influenza a viruses in domestic ducks" 82 : 11374-11382, 2008

15 Yuki, Y., "Mucosal vaccines: Novel advances in technology and delivery" 8 : 1083-1097, 2009

16 Holmgren, J., "Mucosal immunity and vaccines" 11 : 45-53, 2005

17 Brandtzaeg, P., "Let’s go mucosal: Communication on slippery ground" 25 : 570-577, 2004

18 Song, M. S., "Investigation of the biological indicator for vaccine efficacy against highly pathogenic avian influenza (HPAI) H5N1 virus challenge in mice and ferrets" 27 : 3145-3152, 2009

19 Meng, S., "Intranasal immunization with recombinant HA and mast cell activator C48/80 elicits protective immunity against 2009 pandemic H1N1 influenza in mice" 6 : 19863-, 2011

20 Asahi-Ozaki, Y., "Intranasal administration of adjuvant-combined recombinant influenza virus HA vaccine protects mice from the lethal H5N1 virus infection" 8 : 2706-2714, 2006

21 Dormitzer, P. R., "Influenza vaccine immunology" 239 : 167-177, 2011

22 Akdis, M., "Immunologic responses to sublingual allergen immunotherapy" 21 : 71-76, 2008

23 Renegar, K., "Immunoglobulin a mediation of murine nasal anti-influenza virus immunity" 65 : 2146-2148, 1991

24 Song, L., "Efficacious recombinant influenza vaccines produced by high yield bacterial expression: A solution to global pandemic and seasonal needs" 3 : 2257-, 2008

25 Liew, F. Y., "Cross protection in mice infected with influenza a virus by the respiratory route is correlated with local IgA antibody rather than serum antibody or cytotoxic T cell reactivity" 14 : 350-356, 1984

26 Verhoeyen, M., "Antigenic drift between the haemagglutinin of the hong kong influenza strains A/Aichi/2/68 and A/Victoria/3/75" 286 : 771-776, 1980

27 Aguilar-Yanez, J. M., "An influenza A/H1N1/2009 hemagglutinin vaccine produced in Escherichia coli" 5 : 11694-, 2010

28 Reed, L.J., "A simple method of estimating fifty percent endpoints" 27 : 493-497, 1938

29 Hai, R., "A reassortment-incompetent live attenuated influenza virus vaccine for protection against pandemic virus strains" 84 : 6832-6843, 2011

30 Fujihashi, K., "A dilemma for mucosal vaccination: Efficacy versus toxicity using enterotoxin-based adjuvants" 20 : 2431-2438, 2002