Single-dose intranasal administration of AdCOVID elicits systemic and mucosal immunity against SARS-CoV-2 in mice

Abstract

The coronavirus disease 2019 (COVID-19) pandemic has highlighted the urgent need for effective preventive vaccination to reduce burden and spread of severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) in humans. Intranasal vaccination is an attractive strategy to prevent COVID-19 as the nasal mucosa represents the first-line barrier to SARS-CoV-2 entry before viral spread to the lung. Although SARS-CoV-2 vaccine development is rapidly progressing, the current intramuscular vaccines are designed to elicit systemic immunity without conferring mucosal immunity. Here, we show that AdCOVID, an intranasal adenovirus type 5 (Ad5)-vectored vaccine encoding the receptor binding domain (RBD) of the SARS-CoV-2 spike protein, elicits a strong and focused immune response against RBD through the induction of mucosal IgA, serum neutralizing antibodies and CD4+ and CD8+ T cells with a Th1-like cytokine expression profile. Therefore, AdCOVID, which promotes concomitant systemic and local mucosal immunity, represents a promising COVID-19 vaccine candidate.

Safety and Immunogenicity of a Novel Intranasal Influenza Vaccine (NasoVAX): A Phase 2 Randomized, Controlled Trial

“…Following administration of NasoVAX, the vector infects epithelial cells of the nasal cavity and upper respiratory tract, where the antigen is expressed in the absence of viral replication. The expressed antigen can then be presented to the immune system through the HLA class I antigen processing machinery, leading to antiviral CD8+ T cell responses as observed in other studies [20]. The substantially greater T cell response associated with NasoVAX compared to the inactivated influenza vaccine comparator is consistent with the potential for Ad5 vectors to activate a systemic cellular immune response greater than other human adenovirus serotype vaccines [21].…”

“…It is possible there may be a threshold for immune activation required to stimulate T cell responses, but additional studies will likely be required to understand the cellular response to NasoVAX. While not evaluated in this study, mucosal administration of Ad5 vectors promotes the establishment of resident memory T cells in preclinical models [ 20 ], a cell population of emerging importance in protection against invading pathogens, especially in viral infection [ 22 , 23 ].…”

“…NasoVAX is based on a replication-deficient Ad5 vaccine platform technology that is ideally suited for not only rapid development of vaccines, as necessary to meet the evolving strain requirements of a seasonal influenza vaccine, but also valuable in the event of a respiratory virus pandemic, such as the current pandemic caused by severe acute respiratory syndrome virus coronavirus 2 (SARS-CoV-2). The vaccine attributes described for NasoVAX in this study are likely to translate to other intranasal vaccine candidates based on the same platform technology [ 20 ].…”

Viral Vectors for COVID-19 Vaccine Development

“…Additional studies confirmed that immunization with a 10-fold lower dose (1 × 10 10 Ad5-S-nb2 particles) also conferred protection. In another approach, Ad5 vectors were engineered for the expression of the full-length SARS-CoV-2 S protein, the S1 domain and the RBD [ 39 ]. Intranasal immunization of mice with Ad5 expressing the SARS-CoV-2 S RBD (AdCOVID) elicited strong and focused RBD-specific induction of mucosal IgA, serum neutralizing antibodies and CD4 + and CD8 + T cells with Th1-like cytokine profiles.…”

Application of Viral Vectors for Vaccine Development with a Special Emphasis on COVID-19

“…Finally, intranasal SARS-CoV-2 vaccine delivery is a potential option [ 191 ]. For instance, intranasal administration of an Ad5-based vector expressing the SARS-CoV-2 S receptor binding domain (RBD) elicited strong neutralizing antibody responses [ 192 ] ( Table 3 ).…”