Diphtheria, the public health response and the origins of the childhood immunisation programme in Ireland

In common with most countries, the childhood immunisation programme in Ireland was founded on a successful public health response to diphtheria. The success of the antidiphtheria public health intervention in Ireland has meant that no case of the disease has been recorded in the state for almost fifty years. This is a significant achievement considering that diphtheria continues to appear annually in many European states, albeit in much reduced numbers on former years. For parents and children of nineteenth, and early twentieth-century Ireland, diphtheria represented the ‘most dreaded disease of childhood’, however, for their modern day counterparts diphtheria is no more than an obscure disease mentioned in leaflets promoting the benefits of childhood immunisation. In Ireland, diphtheria has been consigned to history, and so too have the horrors and mass fatalities once associated with it. But how was this achieved? Was active immunisation received with open arms by public health authorities, the wider medical community, and the general public? This study tackles these questions by undertaking the first historical examination of the issues which underpin the origins of active immunisation in Ireland. It explores the driving forces that shaped the national childhood immunisation programme, and those that opposed them. In addition, it examines the complex social implications attendant on the introduction of this mass public health intervention in an Irish context.

Development of a dissolvable microneedle influenza vaccine patch

Delivery of large molecular weight biological molecules to the epidermis and dermis is constrained by the tough outer layer of the epidermis, the stratum corneum (sc). Microneedle technologies attempt to overcome this physical barrier using sharp micron-size projections to penetrate the sc. Dissolvable microneedles (DMN), are a particular microneedle design whereby the needle structure is composed of a soluble matrix that upon application to the skin, dissolves releasing the vaccine load into skin. This thesis examines (1) the formulation and processing considerations around DMN fabrication, (2) the immunogenicity of DMN containing trivalent influenza vaccine (TIV) in pre-clinical mouse and pig models and (3) the thermostability of these DMN formulations during storage. The results demonstrate the importance of formulation for microneedle formation and mechanical strength. Trehalose and polyvinylalcohol based formulations produced optimal microneedle structures and were amenable to piezoelectric dispensing; allowing for precise multi-layered DMN to be fabricated. The effect of drying conditions was assessed and found to be critical for DMN mechanical strength and skin penetration. The antibody responses to TIV generated by DMN-mediated vaccination were comparable or greater to those induced by immunization with a commercial TIV via the IM route in mice. DMN mediated immunisation resulted in a significantly broader humoral response to heterotypic influenza viruses compared to IM delivery. Stored at 40°C, a licensed seasonal influenza vaccine incorporated into DMN array was thermostable for at least 6 month as determined by Single Radial Immunodiffusion and immunogenicity in mice. The thesis advances the field of DMN influenza vaccination by elucidating important processing and formulation considerations in the fabrication of highly reproducible DMN. It also demonstrated that DMN can induce broader, larger humoral responses than conventional IM administration while demonstrating enhanced accelerated stability. Crucially, this works advances an automated fabrication system that will allow for clinical translation of DMN.