A nasal vaccine candidate based on S2 and N proteins from SARS-CoV-2 generates a broad antibody response systemically and in the lower respiratory tract.

Since the beginning of the COVID-19 pandemic, various groups around the world have intensively worked in the development of vaccine candidates against SARS-CoV-2. Several vaccines have been approved in the past years; the majority is based on the Spike or RBD proteins and employs parenteral administration routes. Considering the recent history of coronavirus zoonotic events, which are known to have caused serious human health problems, the development of vaccines with a broad scope of protection and the potential to cut/reduce the transmission remains in the spotlight. The current global pandemic preparedness initiatives have also promoted the preclinical evaluation of a new group of coronavirus vaccines. In line with current needs, the goal of the present work is the preclinical evaluation, in two different mice strains, of a novel nasal vaccine candidate based on two highly conserved sarbecovirus proteins, S2 and nucleocapsid (N). The vaccine preparation, containing a CpG ODN as adjuvant, was able to generate high antibody titers against both antigens, in sera and bronchoalveolar lavages. This humoral response results cross-reactive to SARS-CoV-1 and MERS-CoV. In addition, the preparation induces IFNγ secretion, and a marked IgG2a response, against both proteins at the systemic compartment, consistent with the development of a Th1 pattern. Although further evaluations should be done, the level of cross-reactivity and the mucosal response obtained constitute promising features of this vaccine candidate.