Issue #45: Virus and vaccine - Part 3

Written by Nobel Laureate Professor Peter Doherty

As discussed over the past couple of months (#36-#43), SARS-CoV-2 invades via the nose and infects epithelial cells in our upper respiratory tract. There it multiplies and turns otherwise dysfunctional cells into virus-producing ‘factories’. New progeny virions released into the bathing mucus layer infect more cells in us, or in others exposed to virus in the microdroplets that we push out into the air. That little 30,000 bases of ‘bad news’ viral RNA may, if our genetics determines that we become superspreaders, transform us from being innocuous, responsible citizens to – using FBI terminology - ‘public enemy Number One’.

Some virions – including damaged virus – will also enter the regional lymphoid tissue of the adenoids, tonsils and cervical lymph nodes where, after processing in specialised antigen presenting cells (APCs) they stimulate a protective immune response. At the same time, infectious virions progress deeper down into our lungs to cause more damage and involve the mediastinal lymph nodes in the middle of the chest. Even worse, the infection can move forward to a viraemic phase, where virions distributed via the blood infect cells in our heart, kidneys and blood vessel walls, trigger micro-clots and strokes and do all sorts of permanent damage.

Right from the time of infection, molecules of the innate immune system, the interferons, cytokines and chemokines, will be trying to hold the virus in check while, at the same time, causing some collateral damage. Vaccines injected into the arm, on the other hand, make only one virus protein, the spike, do not go on to infect other cells, and the response is limited to the axillary lymph nodes in the armpit. Which is preferrable, infection or vaccination? I spent my earlier years in science working as a diagnostic and experimental pathologist. Having stared for hours via light and electron microscopes at the damage viruses can do to our cells and organs, I’ll take whatever vaccine is on offer at the earliest possible opportunity!

The worst I would expect from receiving either vaccine is a sore arm, perhaps at the site of injection and/or in the axillary lymph nodes – there are 20-40 of these – maybe a headache, drowsy but not sleeping well, odd dreams and general discomfort, with that continuing for a day or two. I might take some paracetamol to help me sleep but, in general, I’ll be happy to be having that experience. Why? Because I’ll have the sense that newly made cytokines and chemokines in my blood are causing the neurological component of these symptoms. What ‘feeling off’ is telling me is that the vaccine has induced the production of those innate immune response molecules that help set-up the lymph nodes – by recruiting small lymphocytes (#39) – so that I make a good immune response.

This capacity to cause early discomfort after vaccination is what we refer to as ‘reactogenicity’. Experiencing that with small children – it’s pretty distressing to take a happy kid to the doctor and come away with one that will be whingey and whiney for a couple of days – led to some of the childhood vaccines being ‘improved’ to minimise any immediate, negative consequences. The whooping cough (Pertussis vaccine) was notorious in that regard, but the newer, cleaned up product is much more readily tolerated. The only problem is that it’s not as good a vaccine as the early, ‘dirty’ variety: less pain, less gain!

As mentioned earlier (#43), there have been some problems with acute allergic reactions to the BioNTech/Pfizer (BP)mRNA vaccine. People who are highly allergic may be directed to the AstraZeneca (AZ) alternative. This strategy of administering a large dose of viral mRNA is very novel so far as people are concerned, but the results of clinical trials were carefully scrutinised prior to regulatory approval and, at time of writing, at least one dose of BP – or the comparable Moderna product – has been given to more than million Americans. Similarly, large numbers of people in Brazil and in the UK have received the AZ vaccine with no evidence of any lurking danger to date. Scanning the latest information, I don’t see any reason to doubt as yet that both vaccines protect against the development of severe disease. And, while they may not stop early infection in the nose, my personal guess is that they will greatly reduce the extent of transmission.

At this stage, it’s probably too early to know whether prior infection or vaccination provides better long-term protection. We know that people who had clinically mild COVID-19 can be reinfected (#23, #24) but, with the widespread use of nasal swabs and PCR tests for SARS-CoV-2, we set a higher standard for protection than has ever been applied to any respiratory pathogen. And, though it’s currently a guess on my part, it could be that the best possible, long-term protection would be given by a mild, naturally-acquired infection in a previously vaccinated individual. I’m not suggesting that vaccinated people should try to be infected, but it’s one major reason that I’m not very concerned about the reported 70% versus 90% protective efficacy of the AZ versus the BP vaccines that will soon be rolling out here. The basic message: take whatever vaccine you’re offered at the earliest possible opportunity! You owe that to yourself, to your family, and to your fellow citizens.