Of the nearly 100 SARS-CoV-2 vaccines currently undergoing clinical trials, only seven are delivered intranasally - despite this vaccine type's long success in providing protection from influenza. In a Perspective, Frances Lund and Troy Randall argue that intranasal vaccines could be beneficial in the continued fight against COVID-19, especially considering respiratory viruses like SARS-CoV-2 predominantly enter the nasal passage first. Currently authorized COVID-19 vaccines are delivered via intramuscular injection, where they elicit systemic immune responses and central immune memory. While several versions are currently being administered worldwide, many more are in development. However, according to the authors, given the respiratory propensity of the virus, it is surprising that so few intranasal vaccines, which deliver their antigens directly to the site of infection, are being considered. Here, Lund and Randal discuss the potential of intranasal COVID-19 vaccines, highlighting their advantages, drawbacks and rationale for use over intramuscular options. In addition to being needle-free, intranasal vaccines provide two additional layers of protection compared to intramuscular vaccines. Intranasal vaccine-elicited immunoglobulin A (IgA) and resident memory B and T cells in the nasal passages and upper airways provide a barrier to infection, impede viral replication and reduce viral shedding. Lund and Randall note that effective vaccination strategies need not be restricted to a single delivery system and suggest that an ideal vaccination strategy may consist of an intramuscular vaccine combined with an intranasal booster.
