SARS-CoV-2 oral tablet vaccination induces neutralizing mucosal IgA in a phase 1 open label trial

BackgroundDespite the plethora of efficacious vaccines to the initial Wuhan strain of SARS-CoV-2, these do not induce robust mucosal immunity, offering limited protection against breakthrough infection and replication in the respiratory tract. The mucosa is the first line of defense, therefore a vaccine that induces a mucosal IgA response could be an important strategy in curbing the global pandemic. MethodsWe conducted a single-site, dose-ranging, open-label clinical trial of an oral SARS-CoV-2 vaccine to determine safety and immunogenicity. This tablet vaccine is comprised of a non-replicating adenoviral vector expressing the SARS-CoV-2 Spike and Nucleocapsid genes and a double-stranded RNA adjuvant. 35 adult subjects meeting inclusion/exclusion criteria received a single low (1x1010 IU) or high (5x1010 IU) dose and 5 subjects received two low doses. Nasal, saliva and serum samples were assessed for the presence of IgA, IgG and surrogate neutralizing antibodies. Convalescent subjects between 1-8 months post infection were recruited to give nasal, saliva, and serum samples for comparison. ResultsThe vaccine was well tolerated without any dose-limiting toxicity observed. No serum neutralizing antibodies were observed, but modest IgA responses were seen in serum post immunization. The majority of vaccine recipients had an increase in mucosal secretory IgA which was highly cross-reactive against all coronaviruses tested and persisted up to 360 days. Furthermore, the nasal IgA induced by vaccination has superior neutralizing activity compared to convalescent nasal samples. ConclusionThe vaccine was safe, well tolerated and generated mucosal immune responses including cross-reactive surrogate neutralizing secretory IgA. These results demonstrate the ability of a mucosal vaccine to induce long-lasting mucosal IgA to SARS-CoV-2. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=142 SRC="FIGDIR/small/22277601v1_ufig1.gif" ALT="Figure 1"> View larger version (19K): org.highwire.dtl.DTLVardef@19a3c90org.highwire.dtl.DTLVardef@fe2f7borg.highwire.dtl.DTLVardef@1df5385org.highwire.dtl.DTLVardef@e46bc7_HPS_FORMAT_FIGEXP M_FIG C_FIG