Current progress in pulmonary delivery of measles vaccine

Abstract

Due to the high infectivity of measles virus, achieving sufficient population immunity to interrupt transmission requires two doses of live attenuated measles virus vaccine. Subcutaneous delivery of vaccine by injection requires trained personnel, maintenance of a cold chain and safe disposal of used needles and syringes. Pulmonary vaccine delivery offers the opportunity for cost-savings and improved coverage, but requires re-licensure. Two aerosol vaccine formulations, nebulized liquid and dry powder, and multiple delivery devices have been evaluated in humans and macaques. Nebulized liquid vaccine is effective for a second dose of vaccine in older children, but less effective for primary vaccination of infants. Dry powder vaccine provides solid protection in macaques and boosts responses in immune adults, but has not yet been tested in infants.

Keywords::

• aerosol
• dry powder
• inhalation
• measles virus
• vaccine

Financial & competing interests disclosure

Work from the author's laboratory has been funded by the Bill and Melinda Gates Foundation (FNIH), Becton Dickinson and the NIH. The author has collaborated with Aktiv Dry on development of a dry powder measles vaccine, but has no financial involvement in that company or in any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Measles virus (MeV) is highly infectious, and elimination of transmission requires 92–95% population immunity.

• Achieving a high level of population immunity requires two doses of the live attenuated MeV vaccine, which are currently delivered by subcutaneous injection, and in developing countries, mass campaigns are used to provide the second dose.

• Subcutaneous delivery of the vaccine requires maintenance of a cold chain, trained personnel for reconstitution and injection, and safe disposal of used needles and syringes – all are barriers to maintaining high coverage.

• Aerosol vaccination would diminish these barriers, facilitate both routine vaccination of infants and mass campaigns and be cost-effective.

• For immunogenicity, aerosolized vaccine needs to be delivered as small particles to the deep lung either as a nebulized liquid or dry powder to initiate infection and implementation of pulmonary vaccination requires vaccine relicensure for this route of delivery.

• Both liquid and dry powder vaccines have been formulated using the Edmonston–Zagreb strain of measles vaccine virus and have completed preclinical efficacy and Phase I safety testing.

• Pulmonary delivery of the nebulized liquid vaccine induces seroconversion in 85% of 9- to 11-month-old infants compared with 95% seroconversion for subcutaneous injection, and there is a plan to file for licensure.

• Pulmonary delivery of the dry powder vaccine has not yet been tested for immunogenicity in nonimmune infants.

• Future decisions regarding implementation of pulmonary delivery for routine immunization and mass campaigns will require an optimal balance of ease of delivery, coverage and seroconversion rates.

Notes