Immune response

The resurgence of measles in Europe signals something of a confidence crisis in the area of vaccination, and not for the first time. Mass panics of this sort are not new, but the reach of modern hysteria is aided by technology. Such rapid global spread has propelled vaccine hesitancy into the World Health Organisation's most critical global health threats of 2019.

Of course, like any medical intervention, vaccination comes with the possibility of side effects (even if precisely quantified and well understood). And by their very nature, such interventions are acts taken to prevent a disease an individual does not yet have and may not catch. Human beings can rationalise harms from random misfortune more successfully than those feared self-inflicted, so population-level treatments are an easy target for suspicion. The Anti-Vaccination League railing against compulsory smallpox vaccination in the 1800's is part of a more-or-less unbroken line to the anti-vax movements of today, motivated by fear of tinkering with their concept of the natural order.

And yet, vaccination is not an unnatural technology. Humanity has always unknowingly innoculated itself against disease, and has been knowingly doing so for many hundreds of years. The concept wasn't discovered solely by Edward Jenner or any one individual. In fact, deliberate innoculation, or variolation, as known against the Variola (smallpox) virus, originated hundreds of years earlier in China. That this and similar practices cropped up across the world, demonstrates that such techniques are a natural consequence of our observation of cause and effect, much like applying pressure to stanch bleeding or cleaning a wound to prevent infection. Of course, as with any long-practised technique, vaccination evolves.

Sometimes, this evolution happens when scientists discover that the underpinnings of a hard-to-treat disease are inoculable. Such is the story of the links between cervical cancer and HPV. In some ways this is a traditional application of a vaccine to a pathogen, but getting there required cutting through a thicket of myths to eventually find and isolate the human virus in sufficient scale to create the vaccine itself. It may be early days for mass rollout of the HPV vaccine, but only one decade on the impact is glaringly obvious: this treatment drastically reduces the incidence of cervical cancer, and may ultimately eliminate the most common forms of the disease.

Another type of evolution is in the application of vaccination to internal proteins normally hidden from our immune system. Overcoming this "self-barrier" is important if we wish to mount an immune response to cases where our body produces something harmful, such as cancerous cells or toxic proteins. One disease targeted by such a vaccine is Alzheimer's disease. Alzheimer's presents a worthwhile target due to the role played in the disease by neurotoxic proteins. Were a vaccine able to safely prevent or clear such proteins, the thinking goes that we might have a treatment for a previously intractable condition. Early indicators from the phase 2 trials appear positive. However, this treatment arises from the so-called amyloid-cascade hypothesis, the dominant Alzheimer's research model for many years, but one which failed to produce successful treatments until the recent controversy around the drug aducanumab. Vaccines targeting endogenous proteins remain an important technology in any case, since they may be stepping stones towards future breakthroughs, such as for Parkinson's disease and the neurological disorder CTE.

Before we leave the discussion of vaccines, a condition of interest to longevity practitioners seeking to understand the drivers of excess mortality is the influenza virus. This has been examined within a European context within recent years, and vaccines are now routinely offered to the vulnerable. One complexity is knowing whether the vaccine administered will be effective against future viral strains encountered, and this educated guesswork does not always pay off. For this reason, a universal influenza vaccine is much sought after, and could have a substantial impact not just on excess winter mortality, but also on mitigating a potential future pandemic. One such vaccine is currently in phase 2 trials. Will reduction in deaths from cancer, and progress towards treatments for neurodegenerative disease or pandemic influenza prove compelling enough to put present-day vaccine denial back in its box? Perhaps, but history tells us it won't stay there forever...