None listed
Conditions
Brief summary
In settings such as Australia and New Zealand where measles elimination has been achieved for a decade or more due to sustained high MMR vaccine coverage, cases of measles in young adults who have two documented MMR doses in childhood is increasingly being documented in association with waning measles antibody levels. This study will evaluate whether alternate routes of MMR administration result in superior antibody responses compared to standard intramuscular at one and 12 months in seronegative young adults. This comparative immunogenicity and reactogenicity trial will have three intervention arms - one each for the three different routes of administration of the Priorix Measles-Mumps_Rubella vaccine (MMR; GSK) routinely used in New Zealand. Administration of MMR by aerosol via a vibrating mesh nebuliser (arm 1) will be compared with administration intradermally using a specifically designed microneedle MicronJet600 device (Nanopass) (arm 2) and both will be compared with standard intramuscular administration (arm 3). The study population is young adults documented to have antibodies to either or both of measles and mumps measured by the Diasorin assay which are below the threshold set by the manufacturer for seropositivity despite a history of two previous MMR doses. The working hypothesis is that alternate sites of delivery where attenuated measles, mumps and rubella viruses encounter different immune effector cells are likely to result in greater and more sustained antibody responses. The intradermal device will deliver the vaccine to the skin's dermis, where dendritic cells are plentiful, and the aerosol device will deliver the vaccine to airway and pulmonary mucosal tissue. We will also measure local and systemic adverse reactions for the three delivery techniques.
Interventions
NAME
Administration of measles-mumps-rubella (MMR) vaccine by nebulised aerosol or intradermal device compared with intramuscular route in seronegative previously vaccinated young adults.
WHAT
0.3 mL of MMR vaccine (Priorix GSK) https://www.medsafe.govt.nz/profs/Datasheet/p/Priorixvac.pdf)
will be administered using a vibrating mesh nebuliser manufactured by Aerogen Ltd (Ireland) or the MicronJet600 microneedle device (NanoPass Technologies Ltd) to aid delivery of vaccine intradermally in the
NAME Administration of measles-mumps-rubella (MMR) vaccine by nebulised aerosol or intradermal device compared with intramuscular route in seronegative previously vaccinated young adults. WHAT 0.3 mL of MMR vaccine (Priorix GSK) https://www.medsafe.govt.nz/profs/Datasheet/p/Priorixvac.pdf) will be administered using a vibrating mesh nebuliser manufactured by Aerogen Ltd (Ireland) or the MicronJet600 microneedle device (NanoPass Technologies Ltd) to aid delivery of vaccine intradermally in the upper arm deltoid region. Procedures for use of the Aerogen nebuliser - most commonly used to deliver nebulised drugs - are provided here: https://www.youtube.com/watch?v=3l6yFy0F5zs and for the MicronJet600 microneedle device: https://www.nanopass.com/micronjet-microneedle-device/instructions-for-use/ WHO MMR vaccine will be administered by nurses who are certified immunisation providers. Use of both the Nanopass MicronJet600 device and the Aerogen nebuliser are well within the scope of practice for trained registered nurses and specific training videos are available, supplemented by tailored instructions from the manufacturers HOW Delivery will be during a face-to-face visit using the devices as described above by the staff as described above to individual consenting eligible participants. For participants randomized to the aerosol study arm a study nurse will prepare the 0.3 mL MMR vaccine dose and prepare the single-use Aerogen ultra device. Following instructions, the participant will inhale the vaccine mist using the mouthpiece via slow, natural breathing. The study nurse will assess appropriate aerosol formation and during administration will monitor for completeness of inhaled dose. For participants randomized to the intradermal study arm, the study nurse will prepare the 0.3 mL MMR vaccine dose using the provided sterile vaccine diluent and attach the MicronJet600 needle to the syringe. The dose will be administered in the deltoid region precisely according to the device protocol (45 degree angle, correct orientation and consistent pressure when deploying the dose). For both intervention methods, the participant will be monitored for 30 minutes post-vaccination for any immediate adverse events or reactions. DOCUMENTATION AND REPORTING Adherence to the intervention will be recorded by study staff through use of electronic clinical report forms in the secure study database. This includes a data quality check to verify the randomized intervention assigned was received. Post study, data collection will be monitored for participant adherence to study questionnaires electronically delivered at set time points post-intervention and individual participants followed up in cases of missing data. The receipt of MMR vaccine will also be recorded for each participant in the national immunisation register. WHERE The intervention will be delivered in a clinical setting - a student health service in the University of Otago, Dunedin which has all required infrastructure for delivery of vaccines. TIMING and FREQUENCY of INTERVENTION Administration of MMR vaccine will occur once with four subsequent study visits over the month post-vaccination for sampling and measurements of immune responses by antibody assays in blood and detection of measles vaccine virus in oral fluid by PCR TAILORING For both the aerosol and intradermal intervention study arms, MMR vaccine will be reconstituted to 0.3 mL using the sterile diluent provided with the vaccine, with the only variation being the mode of delivery between the study arms. MODIFICATIONS No modifications are anticipated HOW WELL Delivery of vaccine will be monitored for delivery and any subsequent adverse reactions by study staff
Sponsors
University of Otago
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Prevention
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
17 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* Antibody below threshold for positivity of the Diasorin assay for either or both of measles/mumps antibody and required to have a dose of MMR vaccine by University of Otago Screening and Immunisation Policy * Capable and willing to give written informed consent * Residing in Dunedin * Able and willing to participate for the duration of the study visits and follow-up * Willing to provide verifiable identification at study entry and follow-up visits * Daily access to an internet-connected device (smart phone, tablet, laptop or PC) and willing to complete an electronic diary post vaccination.
Exclusion criteria
Contraindications to MMR as specified in the NZ Immunisation Handbook. These include: • proven anaphylaxis to the vaccine or vaccine component (eg, neomycin or gelatin) • significant immunocompromise: impaired cell-mediated immunity, including untreated malignancy, type 1 interferon receptor (IFNAR) signalling pathway defects, immunosuppressive drug therapy, including high-dose steroids, receiving high-dose radiotherapy, HIV infection with severely impaired T cell immunity • another live vaccine, including Bacillus Calmette-Guérin (BCG), within the previous 4 weeks • pregnant women – pregnancy should be avoided for four weeks after immunization • participants pregnant during study participation may complete follow-up. • intravenous immunoglobulin or blood transfusion during the preceding 11 months
Outcome results
None listed