This gave the impetus for newer sub-unit vaccines to be formulated and tested typically for IM delivery. Empirically, IM jabs of the same vaccine formulations seemed to induce just as strong of an immune response without the inconvenient injection site reaction.

This in turn spurred the search for an alternative route that would be as easy as SC but without its drawback. However, giving such adjuvanted vaccines, SC tended to give strong injection site reactions, which predictably led to complaints and drop-offs in vaccination rates. This discovery became the basis for routinely adding aluminum salts to sub-unit vaccines as an Immunologic adjuvant. The switch away from SC started with research by Alexander Glenny who discovered purified toxins such as from diphtheria and tetanus were more immunogenic when adsorbed on aluminum salts, inducing stronger immune responses ( 1). When a more systematic approach to vaccines took off in the late 19th century, developers simply stuck to the road already traveled by trying to deposit vaccines in the skin, only needles had arrived on the scene by then which made SC injections possible, the only exception being BCG, the tuberculosis vaccine, which empirically seemed to work better as an ID injection. Historically, the oldest vaccines, such as for smallpox, were given by scarification of the skin.

Itpv vaccine