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  • Review Article
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The role of engineered materials in mucosal vaccination strategies

Nature Reviews Materials volume 9, pages 29–45 (2024)Cite this article

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Abstract

Mucosal pathogens, as exemplified by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), human immunodeficiency virus (HIV) and Mycobacterium tuberculosis, lead to substantial morbidity and mortality worldwide and pose serious threats to global health. Mucosal vaccination is crucial to combating mucosal pathogens because it enables the immune system to directly target and neutralize pathogens at their point of entry. Mucosal vaccines need to penetrate the mucus layer, reach the target tissue and activate robust immune responses in the mucosal tissues. Material-based strategies are necessary to meet these requirements. In this Review, we provide an overview of current mucosal vaccines, categorized by administration route, to highlight the importance of material design in overcoming the existing delivery challenges. We discuss the different classes of materials currently being used as vaccine carriers to induce antigen-specific mucosal immunity, including lipids, natural and synthetic polymers, inorganic materials and pathogen-inspired materials.

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Fig. 1: Schematic of type I and II mucosal tissues, and mucosal tissue IgA distribution.
Fig. 2: Vaccine administration routes and delivery vehicles.

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Author notes

  1. These authors contributed equally: Behnaz Eshaghi and Alex Schudel.

Authors and Affiliations

  1. David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA

    Behnaz Eshaghi, Alex Schudel, Ilin Sadeghi, Amy H. Lee, Maria Kanelli, Jooli Han, Bailey Ingalls, Gary Li, Robert Langer & Ana Jaklenec

  2. Department of Immunology, Harvard Medical School, Boston, MA, USA

    Ziqi Chen, Flora Tierney & Ulrich von Andrian

  3. The Ragon Institute of MGH, Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA

    Ziqi Chen, Flora Tierney & Ulrich von Andrian

  4. Independent consultant, GA, USA

    David M. Francis

  5. Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA

    Robert Langer

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  1. Behnaz Eshaghi
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  2. Alex Schudel
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Contributions

B.E., A.S., U.v.A., R.L. and A.J. conceptualized the manuscript. B.E. A.S., I.S. and Z.C. contributed to literature review, manuscript writing and figure composition. A.H.L., M.K., F.T. and D.M.F. contributed to literature review and manuscript writing. B.I. and G.L. contributed to literature review. J.H. contributed to figure visualization. B.E., A.S., U.v.A., R.L. and A.J. edited and finalized the manuscript.

Corresponding authors

Correspondence to Ulrich von Andrian, Robert Langer or Ana Jaklenec.

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R.L. receives licensing fees (to patents on which he was an inventor) from, invested in, consults (or was on Scientific Advisory Boards or Boards of Directors) for, lectured (and received a fee), or conducts sponsored research at MIT for which he was not paid for the following entities: 611 Therapeutics; Abpro International; Acorda (formerly Civitas Therapeutics); Alfred University; Aleph Farms; Alivio Therapeutics; Alkermes; Allevi; Allurion; Alnylam Pharmaceuticals, Inc; Amberstone Bioscience; Amgen; aMoon; Apotex; Arcadia Biosciences, Inc; Arsenal Medical; Artificial Cell Technology, Inc; Avalon-Globocare; Bai Biosciences; BASF Corporation; Bayer; Balzan Foundation; Bexson Biomedical; Bilayer Therapeutics; Biogen; BioInnovation Institute (Novo Nordisk Founden); BioTE Medical; Blackrock; Blackstone (formerly Clarus); Boston Children’s Hospital; CBC Group Investment Mgmt Group; Celanese; Celero; Cellink/BICO; Cellomics Technology LLC; Cellular Biomedical; CE&N/ACS; Charles River Laboratories, Inc.; Clontech Laboratories; Combined Therapeutics (CTx); Conference Forum; Cornell University; Crispr Therapeutics Ag; Crown Bioscience, Inc.; Daré Biosciences (formerly Microchips Biotech, Juniper Pharmaceuticals and Columbia Laboratories); Daros, Inc.; DeepBiome; Dewpoint Therapeutics; Dispendix; Eagle Pharmaceuticals; Earli; Edigene Biotechnology, Inc.; Editas Medicine, Inc.; ELC (Estee Lauder Companies); Eli Lilly; Eisai, Inc.; Entrega; EpiBone; Establishment Labs, SA.; Everlywell; Evox Therapeutics, Ltd.; Fate; Flagship Pioneering; Frequency Therapeutics, Inc.; GeneLeap Biotech; Genemedicine Co Lmtd; GenScript USA, Inc; Geneo Medicine; GENUV; Glaxosmithkline LLC; Glycobia; Glympse Bio; Goldman Sachs; Greenlight Biosciences; HCR (HealthCare Royalty Partners); HKF DNA Technologies; Hopewell Therapeutics; Horizon Discovery Group Plc; Humacyte, Inc.; IBEX Pharmaceuticals, Inc.; Immunai; ImmuneXcite, Inc.; Institute of Immunology Co. Ltd; Integrated DNA Technologies, Inc.; InVivo Therapeutics; IxBio; J.R. Simplot Company; Jnana Therapeutics; Kala Pharmaceuticals; Kallyope, Inc.; Kendall Capital; Kensa; Kodikaz Therapeutics; KAST (Korean Academy of Science and Technology); Ksq Therapeutics, Inc.; Kunlun Capital; Landsdowne Labs; LikeMinds; Lonza; Luminopia, Inc.; Luye (Shandong luye); Lyndra Therapeutics; Lyra Therapeutics (formerly 480 Biomedical); Maurice Marie Janot Award 2020; McGovern Institute; Medikinetics Co., Ltd.; Merck; MGH Ragon Institute; Micelle; Moderna Therapeutics; Momenta; Muse Biotechnologies, Inc.; Mylan; N2Tech; Nanobiosym; Nanobiotix; Neochromosone; Neoteny 4 LLP; NextRNA; Newbridge Ventures LLC; Noveome Biotherapeutics, Inc.; Novo Nordisk; Ohio State University; Olivo (acquired by Shiseido); Ovid Therapeutics; Particles for Humanity; Pfizer, Inc.; Pioneer Hi-Bred International, Inc.; Placon Therapeutics; Polaris Partners; Pontifical Academy of Sciences; Portal Instruments; Preceres LLC (acquired by Monsanto); PrognomIQ, Inc.; Pulmatrix; PureTech; Quris; ReLive; Rensselaer Polytechnic Institute/Department of Chemical and Biological Engineering; Reprocell USA, Inc. (formerly Stemgent); Replay Bio; Rubius Therapeutics; Satellite Bio; SBEF (Seoul Bio Economy Forum); Secant Medical, Inc.; Seer, Inc.; Selecta Biosciences; Senses LLC; Setsuro Tech Inc.; Seventh Sense Biosystems, Inc.; Shenzhen Rice Life Technology, Ltd; Shire Ag; Sigilon; Sigma Aldrich Co. LLC; SiO2 Materials Science; Ske S.R.L.; Soil Culture Solutions LLC (Dba Soilcea); Souffle Therapeutics; SQZ Biotechnologies; StemBioSys, Inc.; SuonoBio; T2 Biosystems; Taconic Biosciences, Inc. (formerly Taconic Farms); Taiwania Capital (Bio-Asia Taiwan Symposium); TARA; Tarveda Therapeutics; Teal Bio; Terasaki Institute; Tesio Pharmaceuticals; Third Rock Ventures; Tiba Biotech LLC; TissiuM (formerly Gecko); Transgenic, Inc.; Translate Bio (formerly Rana Therapeutics, Inc.); Trilink Biotechnologies, Inc.; Unilever (Living Proof); University of Bergen, Norway (Falch Lecture Honorarium); VasoRX; Verseau Therapeutics, Inc.; Virex Health; Vitakey; Vivtex Corporation; Westlake University; Whitehead Institute; Wiki Foods; Xenter; YourBio (formerly 7th Sense Biosystems); Yz Biosciences (Guangzhou), Inc.; Zenomics; ZWI Therapeutics. A.J. receives licensing fees (to patents on which she was an inventor) from, invested in, consults (or was on Scientific Advisory Boards or Boards of Directors) for, lectured (and received a fee), or conducts sponsored research at MIT for which she was not paid for the following entities: Moderna Therapeutics; OmniPulse Biosciences; Particles for Humanity; SiO2 Materials Science; Takeda (formerly Shire Ag); VitaKey. All the other authors declare no competing interests.

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Nature Reviews Materials thanks Dennis Christensen, who co-reviewed with Signe Tandrup Schmidt; Ed Lavelle; and Amirali Popat for their contribution to the peer review of this work.

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Eshaghi, B., Schudel, A., Sadeghi, I. et al. The role of engineered materials in mucosal vaccination strategies. Nat Rev Mater 9, 29–45 (2024). https://doi.org/10.1038/s41578-023-00625-2

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