Current State and Challenges in Developing Oral Vaccines

Overview

Journal Adv Drug Deliv Rev

Specialty Pharmacology

Date 2017 Apr 26

PMID 28438674

Citations 153

Authors

Julia E Vela Ramirez

Lindsey A Sharpe

Nicholas A Peppas

Affiliations

Soon will be listed here.

Abstract

While vaccination remains the most cost effective strategy for disease prevention, communicable diseases persist as the second leading cause of death worldwide. There is a need to design safe, novel vaccine delivery methods to protect against unaddressed and emerging diseases. Development of vaccines administered orally is preferable to traditional injection-based formulations for numerous reasons including improved safety and compliance, and easier manufacturing and administration. Additionally, the oral route enables stimulation of humoral and cellular immune responses at both systemic and mucosal sites to establish broader and long-lasting protection. However, oral delivery is challenging, requiring formulations to overcome the harsh gastrointestinal (GI) environment and avoid tolerance induction to achieve effective protection. Here we address the rationale for oral vaccines, including key biological and physicochemical considerations for next-generation oral vaccine design.

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References

Brayden D, Jepson M, Baird A . Keynote review: intestinal Peyer's patch M cells and oral vaccine targeting. Drug Discov Today. 2005; 10(17):1145-57. DOI: 10.1016/S1359-6446(05)03536-1. View

Ogra P, Faden H, Welliver R . Vaccination strategies for mucosal immune responses. Clin Microbiol Rev. 2001; 14(2):430-45. PMC: 88982. DOI: 10.1128/CMR.14.2.430-445.2001. View

Lai S, Wang Y, Wirtz D, Hanes J . Micro- and macrorheology of mucus. Adv Drug Deliv Rev. 2009; 61(2):86-100. PMC: 2736374. DOI: 10.1016/j.addr.2008.09.012. View

Peterson L, Artis D . Intestinal epithelial cells: regulators of barrier function and immune homeostasis. Nat Rev Immunol. 2014; 14(3):141-53. DOI: 10.1038/nri3608. View

Wilson-Welder J, Torres M, Kipper M, Mallapragada S, Wannemuehler M, Narasimhan B . Vaccine adjuvants: current challenges and future approaches. J Pharm Sci. 2008; 98(4):1278-316. PMC: 8092333. DOI: 10.1002/jps.21523. View

Chabot S, Wagner J, Farrant S, Neutra M . TLRs regulate the gatekeeping functions of the intestinal follicle-associated epithelium. J Immunol. 2006; 176(7):4275-83. DOI: 10.4049/jimmunol.176.7.4275. View

Cone R . Barrier properties of mucus. Adv Drug Deliv Rev. 2009; 61(2):75-85. DOI: 10.1016/j.addr.2008.09.008. View

Morein B, Simons K . Subunit vaccines against enveloped viruses: virosomes, micelles and other protein complexes. Vaccine. 1985; 3(2):83-93. DOI: 10.1016/0264-410x(85)90055-6. View

Summerton N, Welch R, Bondoc L, Yang H, Pleune B, Ramachandran N . Toward the development of a stable, freeze-dried formulation of Helicobacter pylori killed whole cell vaccine adjuvanted with a novel mutant of Escherichia coli heat-labile toxin. Vaccine. 2009; 28(5):1404-11. PMC: 2814929. DOI: 10.1016/j.vaccine.2009.10.147. View

10.

Hu K, Lovgren-Bengtsson K, Morein B . Immunostimulating complexes (ISCOMs) for nasal vaccination. Adv Drug Deliv Rev. 2001; 51(1-3):149-59. DOI: 10.1016/s0169-409x(01)00165-x. View

11.

Uematsu S, Fujimoto K, Jang M, Yang B, Jung Y, Nishiyama M . Regulation of humoral and cellular gut immunity by lamina propria dendritic cells expressing Toll-like receptor 5. Nat Immunol. 2008; 9(7):769-76. DOI: 10.1038/ni.1622. View

12.

Lauring A, Jones J, Andino R . Rationalizing the development of live attenuated virus vaccines. Nat Biotechnol. 2010; 28(6):573-9. PMC: 2883798. DOI: 10.1038/nbt.1635. View

13.

Newsted D, Fallahi F, Golshani A, Azizi A . Advances and challenges in mucosal adjuvant technology. Vaccine. 2015; 33(21):2399-405. DOI: 10.1016/j.vaccine.2015.03.096. View

14.

van Hoek A, Ngama M, Ismail A, Chuma J, Cheburet S, Mutonga D . A cost effectiveness and capacity analysis for the introduction of universal rotavirus vaccination in Kenya: comparison between Rotarix and RotaTeq vaccines. PLoS One. 2012; 7(10):e47511. PMC: 3480384. DOI: 10.1371/journal.pone.0047511. View

15.

Renukuntla J, Vadlapudi A, Patel A, Boddu S, Mitra A . Approaches for enhancing oral bioavailability of peptides and proteins. Int J Pharm. 2013; 447(1-2):75-93. PMC: 3680128. DOI: 10.1016/j.ijpharm.2013.02.030. View

16.

van de Weert M, Hennink W, Jiskoot W . Protein instability in poly(lactic-co-glycolic acid) microparticles. Pharm Res. 2001; 17(10):1159-67. DOI: 10.1023/a:1026498209874. View

17.

Levine M, Ferreccio C, Abrego P, Martin O, Ortiz E, Cryz S . Duration of efficacy of Ty21a, attenuated Salmonella typhi live oral vaccine. Vaccine. 1999; 17 Suppl 2:S22-7. DOI: 10.1016/s0264-410x(99)00231-5. View

18.

McHugh K, Guarecuco R, Langer R, Jaklenec A . Single-injection vaccines: Progress, challenges, and opportunities. J Control Release. 2015; 219:596-609. DOI: 10.1016/j.jconrel.2015.07.029. View

19.

Rodrigo Mora J, Iwata M, Eksteen B, Song S, Junt T, Senman B . Generation of gut-homing IgA-secreting B cells by intestinal dendritic cells. Science. 2006; 314(5802):1157-60. DOI: 10.1126/science.1132742. View

20.

Zhu Q, Talton J, Zhang G, Cunningham T, Wang Z, Waters R . Large intestine-targeted, nanoparticle-releasing oral vaccine to control genitorectal viral infection. Nat Med. 2012; 18(8):1291-6. PMC: 3475749. DOI: 10.1038/nm.2866. View