Thermostability of Measles and Rubella Vaccines in a Microneedle Patch.

Measles and rubella vaccinations are highly effective at reducing disease prevalence; however, logistic issues related to subcutaneous administration and vaccine wastage limit the extent of vaccination coverage. Microneedle (MN) patches can increase coverage by easing logistics through simplified administration and improved stability. This study demonstrates the thermostability of a bivalent measles and rubella vaccine MN patch. Rubella vaccine stability required pH buffering during drying; potassium phosphate buffer at neutral pH was optimal for both vaccines. Screening 43 excipients for their ability to retain potency during drying and storage yielded sucrose-threonine-potassium phosphate buffer formulation at pH 7.5 as an optimal formulation. MN patches made with this formulation had no significant loss of vaccine titer after one month and remained within a one log10 titer loss cutoff after 3 - 4 months at 5°C, 25°C and 40°C. Finally, these patches were shown to be immunogenic in juvenile rhesus macaques. This work demonstrates the potential for MN patches for measles and rubella vaccination to be removed from the cold chain, which is expected to decrease vaccine cost and wastage, and increase vaccination coverage.

Modelling the relative benefits of using the measles vaccine outside cold chain for outbreak response.

INTRODUCTION: Rapid outbreak response vaccination is a strategy for measles control and elimination. Measles vaccines must be stored and transported within a specified temperature range, but this can present significant challenges when targeting remote populations. Measles vaccine licensure for delivery outside cold chain (OCC) could provide more vaccine transport/storage space without ice packs, and a solution to shorten response times. However, due to vaccine safety and wastage considerations, the OCC strategy will require other operational changes, potentially including the use of 1-dose (monodose) instead of 10-dose vials, requiring larger transport/storage equipment currently achieved with 10-dose vials. These trade-offs require quantitative comparisons of vaccine delivery options to evaluate their relative benefits. METHODS: We developed a modelling framework combining elements of the vaccine supply chain - cold chain, vial, team, and transport equipment types - with a measles transmission dynamics model to compare vaccine delivery options. We compared 10 strategies resulting from combinations of the vaccine supply elements and grouped into three main classes: OCC, partial cold chain (PCC), and full cold chain (FCC). For each strategy, we explored a campaign with 20 teams sequentially targeting 5 locations with 100,000 individuals each. We characterised the time needed to freeze ice packs and complete the campaign (campaign duration), vaccination coverage, and cases averted, assuming a fixed pre-deployment delay before campaign commencement. We performed sensitivity analyses of the pre-deployment delay, population sizes, and two team allocation schemes. RESULTS: The OCC, PCC, and FCC strategies achieve campaign durations of 50, 51, and 52 days, respectively. Nine of the ten strategies can achieve a vaccination coverage of 80%, and OCC averts the most cases. DISCUSSION: The OCC strategy, therefore, presents improved operational and epidemiological outcomes relative to current practice and the other options considered.

Evaluation of storing hepatitis B vaccine outside the cold chain in the Solomon Islands: Identifying opportunities and barriers to implementation.

Monovalent Hepatitis B vaccine (HepB) is heat stable, making it suitable for storage outside cold chain (OCC) at 37°C for 1month. We conducted an OCC project in the Solomon Islands to determine the feasibility of and barriers to national implementation and to evaluate impact on coverage. Healthcare workers at 13 facilities maintained monovalent HepB birth dose (HepB-BD) OCC for up to 28days over 7months. Vaccination data were recorded for children born during the project and those born during 7months before the project. Timely HepB-BD coverage among facility and home births increased from 30% to 68% and from 4% to 24%, respectively. Temperature excursions above 37°C were rare, but vaccine wastage was high and shortages common. Storing HepB OCC can increase HepB-BD coverage in countries with insufficient cold chain capacity or numerous home births. High vaccine wastage and unreliable vaccine supply must be addressed for successful implementation.