The preclinical SARS-CoV-2 vaccine collaboration project between ISR (Immune System Regulation AB) and Professor Ali Mirazimi, adjunct professor at the Department of Laboratory Medicine, Karolinska Institutet has now been published in the journal Vaccine. The mucosal immune system is the largest component of the entire immune system, having evolved to provide protection at the main sites of infectious threat: the mucosae. As SARS-CoV- 2 initially infects the upper respiratory tract, its first interactions with the immune system must occur predominantly at the respiratory respiratory tract, during both inductive and effector phases of the response.

However, all authorised COVID-19 vaccines are administered by injection to focus exclusively on the development of serum antibodies and systemic cell-mediated immunity, including innate responses. ISR believe there is a significant role for mucosal immunity and for secretory as well as circulating IgA antibodies in COVID-19. When tested in a preclinical challenge study, using an hACE2 transgenic SARS-CoV-1 mouse model, intranasal and intratracheal administration of ISR52 provided superior protection against severe infection, compared to the subcutaneous injection of the same vaccine.

Inhaled ISR52 elicited both CD4 and CD8 T-cell spike-specific responses, that were maintained for at least 6-months in wild-type mice. The induced IgG and IgA responses cross-reacting with several SARS-CoV-3 variants of concern were detected in the lung and in serum and protected animals, which displayed neutralizing antibodies. Based on results, ISR52 as a dry powder formulation for nasal administration, a product that does not require cold-chain distribution or the use of needle administration, is a good choice for evaluation in a Phase I/II clinical trial.