Mucosal vaccination: onward and upward

ABSTRACT

Introduction

The unique mucosal immune system allows the generation of robust protective immune responses at the front line of pathogen encounters. The needle-free delivery route and cold chain-free logistic requirements also provide additional advantages in ease and economy. However, the development of mucosal vaccines faces several challenges, and only a handful of mucosal vaccines are currently licensed. These vaccines are all in the form of live attenuated or inactivated whole organisms, whereas no subunit-based mucosal vaccine is available.

Areas covered

The selection of antigen, delivery vehicle, route and adjuvants for mucosal vaccination are highly important. This is particularly crucial for subunit vaccines, as they often fail to elicit strong immune responses. Emerging research is providing new insights into the biological and immunological uniqueness of mucosal tissues. However, many aspects of the mucosal immunology still await to be investigated.

Expert opinion

This article provides an overview of the current understanding of mucosal vaccination and discusses the remaining knowledge gaps. We emphasize that because of the potential benefits mucosal vaccines can bring from the biomedical, social and economic standpoints, the unmet goal to achieve mucosal vaccine success is worth the effort.

KEYWORDS:

• Adjuvant
• delivery system
• mucosal immunology
• mucosal vaccine
• subunit vaccine

Article highlights

• Successful mucosal vaccination can lead to the induction of both protective mucosal immunity and sterilizing systemic immunity. This double-layered guard not only can protect the vaccinee but may also reduce the potential of interpersonal transmission.

• Recent scientific advancement in the molecular and cellular understanding of the mucosal immune system opens new doors for the development of novel mucosal vaccines. New adjuvants, delivery systems, and formulations have propelled the progression of several mucosal vaccines and showed promise in pre-clinical and clinical studies.

• Mucosal vaccine development still faces several significant hurdles. These include the intrinsic difficulties in inducing mucosal immunity, the incomplete understanding of the mucosal immune system, the lack of reliable experimental tools and the heightened regulatory restrictions resulting from past incidents.

• Apart from the ability to induce both local and systemic immune responses, mucosal vaccination also offers additional benefits in safety and versatility. Therefore, the outstanding obstacles are worth constant efforts, as they are largely outweighed by the proven advantages.

Declaration of interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

Catherine JY Tsai: conceptualization; writing – original draft; writing – review and editing. Jacelyn MS Loh: creation of figures (figures created with BioRender.com); writing – review and editing. Kohtaro Fujihashi: Funding acquisition; supervision; writing – review and editing. Hiroshi Kiyono: Funding acquisition; writing – review and editing.

Additional information

Funding

The authors involved in this review are supported by the IMSUT International joint research program [K22-3062] (to C. J.-Y.T.), [K23-3044] (to J.M.S.L.); Agency for Medical Research and Development (AMED)-SCARDA [223fa627003h0002] (to KF and HK); Japan Society for the Promotion of Science (JSPS) Postdoctoral Fellowship P20801 (to C. J.-Y.T.); JSPS Grant-in-Aid for Scientific Research Postdoctoral Fellowship (22F20801 to K.F.); JSPS Grant-in-Aid for Scientific Research B (20H03856 to K.F.); JSPS Grant-in-Aid for Scientific Research Challenging Research Pioneering (20K20495 to K.F.); University of California San Diego (UCSD) Digestive Diseases Research Center (DK120515 to H.K.); and a 3 M donation (to H.K.). Sponsors had no control over the interpretation, writing, or publication of this work.