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

Abstract

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 (1×1010 IU) or high (5×1010 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

Adenoviral-Based Vaccine Elicits Robust Systemic and Mucosal Cross-Reactive Responses in African Green Monkeys and Reduces Shedding after SARS-CoV-2 Challenge

“…For example, Flumist, is more effective in young children than in older adults [30]. More consistent results were observed when the adenovirus bypassed the upper respiratory tract and was delivered by aerosol [31] or by oral delivery in the intestine [17].…”

“…This temperature stable rAd5 oral vaccine has been administered to over 500 human subjects, has an excellent safety profile, is well tolerated, and generates robust humoral and cellular immune responses against targeted antigens [14][15][16]. In humans, mucosal responses have been shown to be induced in the intestine and the nose following oral tablet delivery [14,17]. Furthermore, the potency of this mucosal immunization strategy has been demonstrated in an aerosol preclinical hamster SARS-CoV-2 transmission study, where unvaccinated hamsters were protected from disease when co-housed with hamsters that were challenged with virus after mucosal immunization [18].…”

Mucosal delivery of nanovaccine strategy against COVID-19 and its variants

“…In this regard, a single-site, dose-ranging, open-label phase 1 trial of the VXA-CoV-2-1 oral tablet was administered to healthy volunteers aged 18–54 years old (NCT04563702). The results have shown that two oral vaccinations of VXA-CoV-2-1 elicited mucosal secretory IgA in the majority of vaccine recipients, which was highly cross-reactive to variants and persisted for up to 360 days 94 . A phase II clinical trial for dose and age escalation is currently ongoing to evaluate the safety and immunogenicity of VXA-Cov2-1 (NCT 05067933).…”

Human Vaccines & Immunotherapeutics: News July 2022

“…Mucosal immunity was stimulated by the oral tablet vaccine VXA-CoV2–1 (Vaxart) in a Phase 1 trial involving 35 healthy adults. 2 The vaccine, which comprises a non-replicating adenoviral vector expressing the spike and nucleocapsid antigens with a double-stranded RNA adjuvant, elicited IgA antibodies reactive against multiple coronaviruses and persistent for at least one year.…”