Created: Nov 2021
Measles is caused by the infection with the measles virus. It is a highly contagious illness that can be prevented with vaccination. It frequently affects children, sometimes causing serious complications or death. Though measles has been eliminated in parts of the Americas, the disease still persists to varying extents in other parts of the world, so it remains important to keep addressing this disease in research and medicine.
A 2016 paper, Sourimant et al. identified RNA-Dependent RNA Polymerase Complex as a possible target for the future therapies of infections with Morbilliviruses, which is a genus of viruses that measles belongs to. The research team outlined the recent advances in the structural and functional understanding of the polymerase complex of morbilliviruses, showing that it has structural and enzymatic properties which could make it a viable target for anti-measles drugs. Potential drugs could be morbillivirus RdRp inhibitors, such as ERDRP-0519 or inhibitors of Paramyxovirus L Capping Activity, such as AZ-27.
Though measles can be a dangerous illness by itself, complications arising due to infection with this virus could jeopardize the health of the infected even further. In 2019, Watanabe et al. provided new information on the brain infections that can arise due to measles virus. Though it is known that this virus can persist in the central nervous system, leading to fatal neurodegenerative diseases, the mechanism of the virus spreading in the brain has not been elucidated. The researchers showed that the alterations in the ectodomain of the MeV fusion (F) protein, which destabilize the prefusion form of the F protein, making it hyperfusogenic, lets the measles virus spread in the neurons. The team predicts that the crystal structures of the F protein could be used as a template in the future search for viable fusion inhibitors that could be used to treat measles virus brain infections.
Though a decrease in measles incidence has been observed worldwide thanks to increasing the coverage of first and second doses of measles vaccine, improved vaccine delivery methods that overcome current logistic issues are needed to eradicate this disease fully. In 2017, Coughlin et al. proposed elimination or reduction of cold chain requirements for the vaccine, improving injection safety, managing contaminated waste disposal, and limiting the requirement for medically trained individuals in vaccine administration as possible improvements. Another option is to immunize younger infants than currently using an alternative to vaccination, such as immunization via respiratory route (aerosol) and intradermal route. This would protect the children from a younger age, and would be particularly useful in areas heavily affected by measles.
Aerosol route immunization method was researched using nebulized liquid and dry powder vaccine. Aerosolized measles vaccine showed similar immunization strength to the currently administered subcutaneous injections if the exposure time to the nebulized vaccine in infants was increased to 2.5 min (1st dose). The 2nd dose administered for 30s via aerosol showed the same or better performance as compared to the subcutaneous injection. Edmonston-Zagreb vaccine virus strain showed comparable immunogenicity to subcutaneous injection- the best result compared to other vaccine formulations studied (MMR II vaccine and Schwarz strain).
Another researched type of aerosol route immunization was dry powder vaccine, whose great strength is higher thermostability. This means that the cold chain requirement of this type of vaccine can be reduced or eliminated, which would facilitate the efficient and cheap distribution and storage of the vaccine, especially in the areas where access to refrigerators is limited. Puffhaler and BD Solovent devices were shown to be effective in delivering dry powder vaccines in a macaque model. Dry powder measles virus vaccine administered this way to macaques caused an immune response as effective as that in the subcutaneous delivery. Phase 1 clinical trial results of dry powder vaccine formulation are also promising.
One more delivery method holding great promise is the microneedle patch containing dissolving microneedles, whose tips contain the vaccine. This means that the vaccine stability is increased, and the need for sharps or biohazardous waste disposal is eliminated (since the microneedles dissolve in the skin). Moreover, the patch can be administered by minimally trained people, which decreases the need for skilled medical professionals, and thus can increase the availability of the vaccine worldwide, including the developing countries. Measles microneedle patch vaccination was shown to be as effective as subcutaneous injection of the vaccine in prompting antibody and cellular response in macaques. The research on this administration method is still in the preclinical phase (as of 2017).
To summarize, though measles has been almost eliminated in some countries, and its incidence has greatly decreased in others, the research and design of novel therapies and vaccine administration methods aiming to eradicate this disease fully are still underway.
Sourimant, J., & Plemper, R. K. (2016). Organization, Function, and Therapeutic Targeting of the Morbillivirus RNA-Dependent RNA Polymerase Complex. Viruses, 8(9), 251. https://doi.org/10.3390/v8090251
Watanabe S, Shirogane Y, Sato Y, Hashiguchi T, Yanagi Y. New Insights into Measles Virus Brain Infections. Trends Microbiol. 2019 Feb;27(2):164-175. doi: 10.1016/j.tim.2018.08.010. Epub 2018 Sep 13. PMID: 30220445.
Coughlin, M. M., Beck, A. S., Bankamp, B., & Rota, P. A. (2017). Perspective on Global Measles Epidemiology and Control and the Role of Novel Vaccination Strategies. Viruses, 9(1), 11. https://doi.org/10.3390/v9010011