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Review
. 2025 Sep 17:63:127602.
doi: 10.1016/j.vaccine.2025.127602. Epub 2025 Aug 22.

Mucosal COVID-19 vaccines in clinical development

Alina Tscherne  1 , Weina Sun  2 , Sean T H Liu  3 , Florian Krammer  4
Affiliations
Free article
Review

Mucosal COVID-19 vaccines in clinical development

Alina Tscherne et al. Vaccine. .
Free article

Abstract

Mucosal vaccines are designed to elicit both a strong systemic and mucosal immune response gaining importance as the next generation of vaccines to combat the respiratory coronavirus disease 2019 (COVID-19). The ability of these vaccines to induce mucosal immune responses in the upper respiratory tract may allow efficient prevention of infection and transmission, which could potentially reduce virus circulation in the population. In addition, they have the advantage that they can be administered by non-medical personnel and without needles. Several preclinical studies in small animal models and non-human primates, but also early phase clinical studies confirmed the capability of mucosal COVID-19 candidate vaccines to induce long-lasting immunity and to provide protection against an infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In addition to five vaccines which are already approved/licensed, at least 28 mucosal COVID-19 vaccines, based on different vaccine platforms, are currently being tested in clinical trials. However, clinical data for most of the conducted and completed clinical trials are not publicly available yet. In addition, several initiated trials have been terminated or were withdrawn. In this review, we aim to discuss the advantages and disadvantages of mucosal COVID-19 vaccines and to summarize the current status of mucosal COVID-19 vaccines in clinical development, with an emphasis on the most advanced candidates and the key findings observed in preclinical animal models and clinical studies.

Keywords: Clinical trials; Mucosal COVID-19 vaccines; Preclinical testing; SARS-CoV-2.

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Conflict of interest statement

Declaration of competing interest Florian Krammer declares the following conflicts of interest. The Icahn School of Medicine at Mount Sinai has filed patent applications regarding influenza virus vaccines on which FK is listed as inventor. The Icahn School of Medicine at Mount Sinai has filed patent applications relating to SARS-CoV-2 serological assays, NDV-based SARS-CoV-2 vaccines influenza virus vaccines and influenza virus therapeutics which list FK as co-inventor and FK has received royalty payments from some of these patents. Mount Sinai has spun out a company, Kantaro, to market serological tests for SARS-CoV-2 and another company, Castlevax, to develop SARS-CoV-2 vaccines. FK and WS are co-founders and scientific advisory board member of Castlevax. FK has consulted for Merck, GSK, Gritstone, Sanofi, Curevac, Seqirus and Pfizer and is currently consulting for 3rd Rock Ventures and Avimex. The Krammer laboratory is also collaborating with Dynavax on influenza vaccine development.

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