**6. Applications: engineering SIgA for passive immunisation?**

The route of administration of monoclonal antibody therapy is a determining factor in its effectiveness. Vaccination via the systemic route, whilst effective in generating serum responses, often does not mount a sufficient mucosal response [59]. As a result, most systemic vaccines will not protect against initial infection, since host-pathogen interactions mainly occur directly via the mucosa. This highlights a need for mucosal immunisation and by extension passive immunisation with antibodies.

Passive immunisation would involve the topical administration of pathogenspecific SIgA directly to the oral, nasal, respiratory or gastro-intestinal mucosal. This would immediately form an enhanced protective barrier. For example, there has been significant efforts in the search for artificial colostrum—an oral formulation containing mucosal antibodies against disease in neonates, emulating the protective qualities of breastmilk [60].

In animals, orally-administered VHH-SIgA fusions have provided protection against *E.coli* infection superior to their IgG counterparts [61]. This proof-of-concept study shows the exciting applications of passive immunisation and highlights the importance of IgA-based therapy, although it is yet to be replicated in humans. Furthermore, SIgA's heterologous glycan profile is less of a complication if taken via the oral route due to the body's natural oral tolerance to exogenous antigens [62]. However, the pharmacokinetics and stability of SIgA in the human gastric environment may need further consideration and optimization before implementation [63]. Although our understanding of IgA-mucin interactions is still limited, it is a promising field of study nonetheless.
