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Review
. 2022 Feb:76:103841.
doi: 10.1016/j.ebiom.2022.103841. Epub 2022 Jan 24.

Intranasal COVID-19 vaccines: From bench to bed

Aqu Alu  1 , Li Chen  1 , Hong Lei  1 , Yuquan Wei  1 , Xiaohe Tian  2 , Xiawei Wei  3
Affiliations
Review

Intranasal COVID-19 vaccines: From bench to bed

Aqu Alu et al. EBioMedicine. 2022 Feb.

Abstract

Currently licensed COVID-19 vaccines are all designed for intramuscular (IM) immunization. However, vaccination today failed to prevent the virus infection through the upper respiratory tract, which is partially due to the absence of mucosal immunity activation. Despite the emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, the next generation of COVID-19 vaccine is in demand and intranasal (IN) vaccination method has been demonstrated to be potent in inducing both mucosal and systemic immune responses. Presently, although not licensed, various IN vaccines against SARS-CoV-2 are under intensive investigation, with 12 candidates reaching clinical trials at different phases. In this review, we give a detailed description about current status of IN COVID-19 vaccines, including virus-vectored vaccines, recombinant subunit vaccines and live attenuated vaccines. The ongoing clinical trials for IN vaccines are highlighted. Additionally, the underlying mechanisms of mucosal immunity and potential mucosal adjuvants and nasal delivery devices are also summarized.

Keywords: Adjuvant; COVID-19; Intranasal vaccine; Mucosal; SARS-CoV-2.

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Conflict of interest statement

Declaration of interests The authors declare that they have no conflicts of interests.

Figures

Fig 1
Figure 1
Mucosal immune responses induced by IN vaccination. SARS-CoV-2 antigens uptake by M cells occurs in NALT and leads to the local induction of immune responses. DCs and macrophages rapidly absorb the antigens and present them to CD4+ or CD8+ T cells in mucosal lymphoid tissues. CD4+T cells then induce immunoglobulin-committed B cells to plasm cells that secrete immunoglobulins in blood. The produced IgA will diffuse into the lumen whereas IgG and IgM would neutralize viruses in the blood. Activated DCs/macrophages can also migrate to draining lymph nodes to prime antigen-specific CD4+ and CD8+T cells. Stimulated lymphocytes proliferate and migrate from lymph nodes, distribute to peripheral blood and finally localize at mucosal effector sites to develop a tissue-resident phenotype. Created with BioRender.com.
Fig 2
Figure 2
Current progress in the development of IN vaccines for COVID-19. Different types of IN vaccines have been developed for COVID-19, including virus-vectored vaccines, protein subunit vaccines and others. Virus-vectored IN vaccines are under most intensive investigations, especially adenovirus-vectored vaccines. IN vaccines can induce strong immune responses against SARS-CoV-2, including mucosal (sIgA), humoral (IgM, and IgG), and cellular immune responses, which can protect immunized animals or humans against SARS-CoV-2 infection and transmission. Created with BioRender.com.
Fig 3
Figure 3
A schematic illustration of mucosal adjuvants for IN vaccines. Created with BioRender.com.
See this image and copyright information in PMC

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