Intranasal vaccines for SARS-CoV-2: From challenges to potential in COVID-19 management

[Display omitted] •Intranasal vaccines provide sterilizing immunity to both upper and lower respiratory tract.•IgA mediated localized mucosal immune protection is possible along with systemic immune responses.•A nasal vaccine spray, unlike an injection, is painless and appealing to needle-phobic population•Critical intranasal formulation factors include pH, mucoadhesion, nasal mucosal irritation and toxicity.•Intranasal platforms exhibit versatility for both, prophylaxis and treatment against SARS-CoV-2. Unlike conventional Coronavirus 2019 (COVID-19) vaccines, intranasal vaccines display a superior advantage because the nasal mucosa is often the initial site of infection. Preclinical and clinical studies concerning intranasal immunization elicit high neutralizing antibody generation and mucosal IgA and T cell responses that avoid severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in both; the upper and lower respiratory tract. A nasal formulation is non-invasive with high appeal to patients. Intranasal vaccines enable self-administration and can be designed to survive at ambient temperatures, thereby simplifying logistical aspects of transport and storage. In this review, we provide an overview of nasal vaccines with a focus on formulation development as well as ongoing preclinical and clinical studies for SARS-CoV-2 intranasal vaccine products.