The Grand Challenge of Aerosolised Vaccines

Despite the development of effective vaccines, many human populations are currently at the mercy of numerous endemic viral pathogens. Measles virus is one such pathogen that, in 2008, was responsible for 164,000 deaths; the worst effected areas are South-East Asia and Africa (WHO stats can be found here). You might find this surprising as there is currently a very good measles vaccine in use – in fact you probably received at some point during childhood and are protected from future infection. Measles cases have been significantly reduced in the developed world, so why hasn’t this vaccine allowed for the eradication of measles virus transmission in the developing world?

Needle vaccination against measles

The key to controlling measles – and other viruses – is to generate sustained high levels of good quality immunity within a population so that the virus can no longer successfully infect and has nowhere to go; this is known as herd-immunity. The problem then is, well why can’t we achieve the herd immunity required to prevent virus transmission? In places like Africa, where people are reminded daily of the horror of measles, you don’t have to force them to accept vaccination unlike what was seen in the UK and US recently so they are readily vaccinated. One problem however, appears to be the mode of vaccination, that is injecting the virus vaccine creates hurdles to a successful immunisation campaign:

·      Trained healthcare workers are required to safely administer the vaccine when it is injected

·      The currently used vaccine formulation tends to go off in temperatures ~ 37 degrees Celsius causing problems for transport and storage especially in areas such as Africa.

·      The use of used/contaminated needles may facilitate the problems of blood-borne diseases and drug use

Are there any alternatives to needle vaccination?

There are of course other ways to vaccinate people, maybe the respiratory tract or the gastrointestinal tract may make better options – especially considering how different injecting a virus is to most of their natural entry mechanism. The mucosa-associated lymphoid tissue, lining the mucosal epithelium of thegastrointestinal and respiratory tracts may also prove to be a more effective place to induce stronger immune responses.

Currently, some 3million children have already been successfully vaccinated from measles using a ‘wet’ aerosol delivery system, however the formulation was unstable above 4 degrees Celsius and delivery was difficult. A recent paper published in PNAS has sought to improve upon this current measles vaccination technology (and also get around the problems of injecting vaccines) through the generation of a highly immunogenic respiratory-delivered ‘dry’ vaccine formulation. It was tested in macaques, can be administered as a single dose and is a highly thermostable, powdered formulation.

'PuffHaler' aerosol delivery system for 'dry' vaccines

 So, how good is it?

They report that their aerosol-delivered vaccines were deposited into the upper and lower respiratory tracts and resulted in the generation of good-quality measles virus specific humoral (B cell + antibody) and cellular (CD8+/CD4+ T cells) immune responses without safety concerns; there also exists a long-lived (<1 year) B cell memory function (and some T cell memory) correlating with long-term virus protection. They show the their vaccine strategy allows for the successful protection from subsequent measles virus challenge. Through comparisons with injected vaccine, the group were able to show that indeed all routes of vaccination generated the required level and quality of immunity required to protect from measles but given other concerns with injecting vaccine aerosol delivery may prove better. These results indicate that this proof of concept, novel vaccine may be comparable to the previously used formulation – although human studies would have to be carried out.

Aersoal delivery system

Scientists are being allowed to investigate problems like these only through being funded by the 'Grand Challenge in Global Health Grants' via the Bill and Melinda Gates Foundation; the money supplied allows for the development of better, safer and ultimatey more cost-effective vaccines. This work highlights the importance in the development of these new and more effective vaccine technologies in order to facilitate the eradication of viral pathogens worldwide. How might this method of administration affect other vaccines, only further work will decide but if we are unable to prevent measles transmission with a highly effective vaccine then what hope do we have to prevent other, less well-studied viruses without decent vaccines?

Lin, W., Griffin, D., Rota, P., Papania, M., Cape, S., Bennett, D., Quinn, B., Sievers, R., Shermer, C., Powell, K., Adams, R., Godin, S., & Winston, S. (2011). Successful respiratory immunization with dry powder live-attenuated measles virus vaccine in rhesus macaques Proceedings of the National Academy of Sciences DOI: 10.1073/pnas.1017334108