Immune Netw.  2013 Jun;13(3):81-85. 10.4110/in.2013.13.3.81.

Sublingual Delivery of Vaccines for the Induction of Mucosal Immunity

• Shim BS
• Choi Y
• Cheon IS
• Song MK

• KMID: 2150770
• DOI: http://doi.org/10.4110/in.2013.13.3.81

Abstract

The mucosal surfaces are constantly exposed to incoming pathogens which can cause infections that result in severe morbidity and/or mortality. Studies have reported that mucosal immunity is important for providing protection against these pathogens and that mucosal vaccination is effective in preventing local infections. For many years, the sublingual mucosa has been targeted to deliver immunotherapy to treat allergic hypersensitivities. However, the potential of vaccine delivery via sublingual mucosal has received little attention until recently. Recent studies exploring such potential have documented the safety and effectiveness of sublingual immunization, demonstrating the ability of sublingual immunization to induce both systemic and mucosal immune responses against a variety of antigens, including soluble proteins, inter particulate antigens, and live-attenuated viruses. This review will summarize the recent findings that address the promising potential of sublingual immunization in proving protection against various mucosal pathogens.

Keyword

Mucosal immune responses; Lung immunity; Parenteral immunization; Sublingual (s.l.) immunization; Vaccine

MeSH Terms

Hypersensitivity
Immunity, Mucosal
Immunization
Immunotherapy
Mucous Membrane
Proteins
Vaccination
Vaccines
Proteins
Vaccines

Reference

1. Holmgren J, Czerkinsky C. Mucosal immunity and vaccines. Nat Med. 2005. 11:4 Suppl. S45–S53.

2. Cuburu N, Kweon MN, Song JH, Hervouet C, Luci C, Sun JB, Hofman P, Holmgren J, Anjuere F, Czerkinsky C. Sublingual immunization induces broad-based systemic and mucosal immune responses in mice. Vaccine. 2007. 25:8598–8610.

3. Cuburu N, Kweon MN, Hervouet C, Cha HR, Pang YY, Holmgren J, Stadler K, Schiller JT, Anjuére F, Czerkinsky C. Sublingual immunization with nonreplicating antigens induces antibody-forming cells and cytotoxic T cells in the female genital tract mucosa and protects against genital papillomavirus infection. J Immunol. 2009. 183:7851–7859.

4. Kim S, Joo DH, Lee JB, Shim BS, Cheon IS, Jang JE, Song HH, Kim KH, Song MK, Chang J. Dual role of respiratory syncytial virus glycoprotein fragment as a mucosal immunogen and chemotactic adjuvant. PLoS One. 2012. 7:e32226.

5. Park HJ, Ferko B, Byun YH, Song JH, Han GY, Roethl E, Egorov A, Muster T, Seong B, Kweon MN, Song M, Czerkinsky C, Nguyen HH. Sublingual immunization with a live attenuated influenza a virus lacking the nonstructural protein 1 induces broad protective immunity in mice. PLoS One. 2012. 7:e39921.

6. Shim BS, Choi JA, Song HH, Park SM, Cheon IS, Jang JE, Woo SJ, Cho CH, Song MS, Kim H, Song KJ, Lee JM, Kim SW, Song DS, Choi YK, Kim JO, Nguyen HH, Kim DW, Bahk YY, Yun CH, Song MK. Sublingual administration of bacteria-expressed influenza virus hemagglutinin 1 (HA1) induces protection against infection with 2009 pandemic H1N1 influenza virus. J Microbiol. 2013. 51:130–135.

7. Shim BS, Choi YK, Yun CH, Lee EG, Jeon YS, Park SM, Cheon IS, Joo DH, Cho CH, Song MS, Seo SU, Byun YH, Park HJ, Poo H, Seong BL, Kim JO, Nguyen HH, Stadler K, Kim DW, Hong KJ, Czerkinsky C, Song MK. Sublingual immunization with M2-based vaccine induces broad protective immunity against influenza. PLoS One. 2011. 6:e27953.

8. Shim BS, Stadler K, Nguyen HH, Yun CH, Kim DW, Chang J, Czerkinsky C, Song MK. Sublingual immunization with recombinant adenovirus encoding SARS-CoV spike protein induces systemic and mucosal immunity without redirection of the virus to the brain. Virol J. 2012. 9:215.

9. Brandtzaeg P. Mucosal immunity: induction, dissemination, and effector functions. Scand J Immunol. 2009. 70:505–515.

10. Yuki Y, Kiyono H. New generation of mucosal adjuvants for the induction of protective immunity. Rev Med Virol. 2003. 13:293–310.

11. Hervouet C, Luci C, Cuburu N, Cremel M, Bekri S, Vimeux L, Marañon C, Czerkinsky C, Hosmalin A, Anjuère F. Sublingual immunization with an HIV subunit vaccine induces antibodies and cytotoxic T cells in the mouse female genital tract. Vaccine. 2010. 28:5582–5590.

12. Song JH, Nguyen HH, Cuburu N, Horimoto T, Ko SY, Park SH, Czerkinsky C, Kweon MN. Sublingual vaccination with influenza virus protects mice against lethal viral infection. Proc Natl Acad Sci U S A. 2008. 105:1644–1649.

13. Viswanathan RK, Busse WW. Allergen immunotherapy in allergic respiratory diseases: from mechanisms to meta-analyses. Chest. 2012. 141:1303–1314.

14. Calderón MA, Casale TB, Togias A, Bousquet J, Durham SR, Demoly P. Allergen-specific immunotherapy for respiratory allergies: from meta-analysis to registration and beyond. J Allergy Clin Immunol. 2011. 127:30–38.

15. Kildsgaard J, Brimnes J, Jacobi H, Lund K. Sublingual immunotherapy in sensitized mice. Ann Allergy Asthma Immunol. 2007. 98:366–372.

16. Brimnes J, Kildsgaard J, Jacobi H, Lund K. Sublingual immunotherapy reduces allergic symptoms in a mouse model of rhinitis. Clin Exp Allergy. 2007. 37:488–497.

17. Agostinis F, Tellarini L, Canonica GW, Falagiani P, Passalacqua G. Safety of sublingual immunotherapy with a monomeric allergoid in very young children. Allergy. 2005. 60:133.

18. Olaguíbel JM, Alvarez Puebla MJ. Efficacy of sublingual allergen vaccination for respiratory allergy in children. Conclusions from one meta-analysis. J Investig Allergol Clin Immunol. 2005. 15:9–16.

19. Larsen TH, Poulsen LK, Melac M, Combebias A, Andre C, Malling HJ. Malling. 2006. Safety and tolerability of grass pollen tablets in sublingual immunotherapy--a phase-1 study. Allergy. 2006. 61:1173–1176.

20. Huo Z, Bissett SL, Giemza R, Beddows S, Oeser C, Lewis DJ. Systemic and mucosal immune responses to sublingual or intramuscular human papilloma virus antigens in healthy female volunteers. PLoS One. 2012. 7:e33736.