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Review
. 2023 Aug:61:101334.
doi: 10.1016/j.coviro.2023.101334. Epub 2023 May 11.

Adenoviral-vectored next-generation respiratory mucosal vaccines against COVID-19

Sam Afkhami  1 , Alisha Kang  1 , Vidthiya Jeyanathan  1 , Zhou Xing  2 , Mangalakumari Jeyanathan  3
Affiliations
Review

Adenoviral-vectored next-generation respiratory mucosal vaccines against COVID-19

Sam Afkhami et al. Curr Opin Virol. 2023 Aug.

Abstract

The world is in need of next-generation COVID-19 vaccines. Although first-generation injectable COVID-19 vaccines continue to be critical tools in controlling the current global health crisis, continuous emergence of SARS-CoV-2 variants of concern has eroded the efficacy of these vaccines, leading to staggering breakthrough infections and posing threats to poor vaccine responders. This is partly because the humoral and T-cell responses generated following intramuscular injection of spike-centric monovalent vaccines are mostly confined to the periphery, failing to either access or be maintained at the portal of infection, the respiratory mucosa (RM). In contrast, respiratory mucosal-delivered vaccine can induce immunity encompassing humoral, cellular, and trained innate immunity positioned at the respiratory mucosa that may act quickly to prevent the establishment of an infection. Viral vectors, especially adenoviruses, represent the most promising platform for RM delivery that can be designed to express both structural and nonstructural antigens of SARS-CoV-2. Boosting RM immunity via the respiratory route using multivalent adenoviral-vectored vaccines would be a viable next-generation vaccine strategy.

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Conflict of interest statement

Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Z.X. is one of the inventors on a patent application PCT/CA2022/051107, entitled “Novel COVID vaccine and method for delivery”. All other authors declare no competing interests.

Figures

Figure 1
Figure 1
Differential geographical localization and types of immune responses following first- and next-generation COVID-19 vaccines. Current first-generation injectable COVID-19 vaccines generate robust systemic humoral and T-cell responses but suboptimal magnitude of antibody responses and no T-cell responses at the respiratory mucosa compared with natural infection. Importantly, while structural and nonstructural SARS-CoV-2 protein-specific immune responses are induced by natural infection, injectable vaccines are designed to generate only spike-specific immune responses. This is reflected by relatively less efficiency in protecting against infection by first-generation COVID-19 vaccines compared with prior natural infection. In contrast, AdV multivalent COVID-19 vaccines, which are safe and amenable for respiratory mucosal delivery, can induce long-lived tripartite immunity at the respiratory mucosa capable of not only protecting against SARS-CoV-2 VOC but also reducing viral transmission and mitigating the development of PACS/long COVID.
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