Why our T cells could take out anxiety about whether the vaccines are effective: new variants or not!

As vaccine rollout grows apace, the media are full of concerns that vaccines may not protect everyone, and may prove much less useful against new variants of the Covid-19 virus.  The EU announced this afternoon support for researching new vaccines. In this post, however, I want to give a fuller introduction to the less well-known aspect of our immunity: our T cells; and why these cells will do the necessary so that even current vaccines should be effective against the new variants.

A quick refresher on antibodies and Covid-19 

• Antibodies* are produced a few days after we become infected and neutralise the foreign proteins carried on the surface of the Covid-19 virus
• The most important of these proteins is the spike protein which is how the virus attaches itself to our cells
• Following naturally acquired Covid-19 infection, we produce antibodies; the worse the infection the more the antibodies, although those with a very severe infection may have their immune system ‘paralysed’
• After the infection has settled, antibodies wane and may disappear after a few months
• The current licensed vaccines act in different ways but all work by getting the body to produce large quantities of neutralising antibodies against this spike protein
• Either from a natural infection or vaccination (or both), the B cells that produce these antibodies have a memory (very useful!) so they can ramp up production of fresh antibodies when faced with a new infection

*And in case I forget to mention this later on, antibodies are produced by cells called B cells

• We do know
  • Up to now, a second natural infection is very uncommon, which is evidence that  natural immunity does provide future protection
  • The vaccines all produce very high levels of neutralising antibodies and in clinical trials these are sufficient to:
    • Virtually eliminate deaths or very serious complications if we do become infected
    • Substantially reduce the need to be hospitalised if we do become infected
    • Substantially reduce the overall number of people in the population who are infected, although without reducing the number with asymptomatic infections 

• We do not know for sure
  • How effective antibodies following vaccination are against new variants but:
    • It seems that sufficient neutralising antibodies are produced to stop serious consequences of infection
    • The well-publicised, small, and not peer-reviewed, study from South Africa also suggested the AstraZeneca vaccine may not prevent mild illness in young people
  • How long the antibody response could remain active for, without needing a third dose of vaccine

Let’s look at T cells!

• I like this picture which shows the  large T cell doing its stuff against the smaller Covid-19 virus (they are the blue cauliflower looking blobs!)

A simple guide to how do T cells work:

• T cells respond to getting a message that there is a foreign protein (such as from the virus)
• There are two types of T cells: ‘Helper’ and ‘Killer’

• What we know about how T cells work after natural infection and vaccines 
  • There has been a lot of research as to how long after an infection the T cell responses continue to work
    • My reading is that the T cell responses are less likely to wane than the antibody response 
    • Interestingly these T cell responses in some people may be present from contact in the past from other coronaviruses – in particular, from the 2003 SARS epidemic
  • In laboratory testing, all the vaccines produced very strong T cell responses
  • Although we need longer-term data, the T cell responses following vaccination last as long as, and possibly longer than, the antibody response.

Why T cell responses may be more resilient to new variants

• Firstly, the T cell system responds to many of the different bits of foreign proteins whereas the antibody is response is more focused
• Why is this important?
  • Scientists estimate that perhaps we will produce separate T cells against may be 15-20 different bits of the spike protein 
  • Given this number of different T cells, they can then fight the virus on all these different fronts – making it much harder for any new variant to completely escape 
  • This is all hypothetical, are there real-life data?
• Secondly, there was an interesting paper published last week from looking at results of vaccines

• They studied people who had been vaccinated 
  • They research looked in detail at how their T cells responded
  • They found that the response by T cells to the spike protein generated from the vaccines was much  broader than that resulting from natural infection
  • They concluded from their results, that these T cell responses would still be active against the spike protein seen in the South African or related variants
• My conclusion: OK I’ll be cautious – laboratory data is not the same as evidence from real live patients; but in theory our T cell responses to vaccines should be good enough to protect against new variants
• Trying to put this all together my take is as follows:
  • T cells work once the virus seriously invades cells.
  • T cell response following vaccines might therefore not be expected to stop the early stages of infection from new (or indeed old) variants
  • However, T cell response following vaccines could be sufficient to stop the infection being severe from any of the known variants

One final piece of exciting news on the horizon 

• As mentioned, all the information above relates to the spike protein, this is because
  • all the licensed vaccines are directed against the spike protein
  • this is where the mutations are in the new variants 
• New vaccines are now being developed (by biotech companies such as Grimstone) to produce T cell responses against a broader range of proteins

• Thus whatever mutations may appear in the spike protein, such new T cell based vaccines will have loads of other targets to attack the virus with
• What I liked was the reported comment from Gritstone’s CEO, that they were happy to do this development but hoping that this might not be necessary because our T cell responses to the current vaccines would be enough!

(Acknowledgment: much of the material in this blog is based on the excellent piece in Nature by Heidi Ledford: https://www.nature.com/articles/d41586-021-00367-7 )

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