A Thermostable Oral SARS-CoV-2 Vaccine Induces Mucosal and Protective Immunity

BELLIER, BERTRAND; SAURA, ALICIA; LUJÁN, LUCAS A.; MOLINA, CECILIA R.; LUJÁN, HUGO D.; KLATZMANN, DAVID

Frontiers in Immunology

Frontiers

Lugar: Basilea; Año: 2022 vol. 13

An ideal protective vaccine against SARS-CoV-2 should not only be effective in preventingdisease, but also in preventing virus transmission. It should also be well accepted by thepopulation and have a simple logistic chain. To fulfill these criteria, we developed athermostable, orally administered vaccine that can induce a robust mucosal neutralizingimmune response. We used our platform based on retrovirus-derived enveloped virus-likeparticles (eVLPs) harnessed with variable surface proteins (VSPs) from the intestinalparasite Giardia lamblia, affording them resistance to degradation and the triggering ofrobust mucosal cellular and antibody immune responses after oral administration. Wemade eVLPs expressing various forms of the SARS-CoV-2 Spike protein (S), with orwithout membrane protein (M) expression. We found that prime-boost administration ofVSP-decorated eVLPs expressing a pre-fusion stabilized form of S and M triggers robustmucosal responses against SARS-CoV-2 in mice and hamsters, which translate intocomplete protection from a viral challenge. Moreover, they dramatically boosted the IgAmucosal response of intramuscularly injected vaccines. We conclude that ourthermostable orally administered eVLP vaccine could be a valuable addition to thecurrent arsenal against SARS-CoV-2, in a stand-alone prime-boost vaccination strategyor as a boost for existing vaccines.