Thread by @RajeevJayadevan

Evidence that T cell immunity generated by vaccine is not fooled by mutations or variants

Study from India shows CD4 & CD8 T cell response was conserved for delta & for the older version of the virus.

This is because there are UNCHANGEABLE parts of the spike protein.

1/16

https://twitter.com/dbtindia/status/1465610775238643712

For those new to immunology, broadly speaking:

🔹Neutralising antibody levels correlate with protection from infection in the nose and throat, while T cell Immunity guards against organ damage and severe disease.

Will explain below 👇

2/

🌳 Imagine the spike protein to be a mango tree. Antibodies target the fruit, while T cells target large branches. Mutations are like mangoes that change their appearance. Hence, a few antibodies can get ‘fooled’.

But the branches are unchanged; hence T cells work as usual.

3/

What most people do not emphasise is that it is not only the neutralising antibodies that are important. It is true that some mutations do affect neutralising antibodies.

However there are hundreds of other antibodies (“binding”) targeted at other parts of the spike protein.

4/

Neutralising antibodies are primarily involved with preventing the virus from getting inside our cells. They prevent infection.

T cells come to our rescue when the virus has gotten past these antibodies and has entered the cells. T cells detect and destroy infected cells.

5/

Thus, T cells not only prevent the virus from spreading from cell to cell, but also protect our organs from damage.

In other words, neutralising antibodies are good at stopping the infection from occurring, while T cells help in preventing organ damage (simplification).

5/

There are numerous other antibodies - apart from “neutralising antibodies”. These appear within 10 days of the 1st dose, along with T cells.

These “binding antibodies” recognise multiple parts of the spike protein, tagging it for our immune system to easily detect & destroy.

6/

Even after the total antibody level (neutralising and binding type) drops after a few months, a small baseline level is maintained. Importantly, an extensive library of memory cells is kept waiting to respond to any infection in the future.

7/

Coming back to the study, this was a “test-negative case-control study” design, which showed that vaccines are effective at reducing infection as well as severe disease.

🔹What is also interesting is that the first dose of vaccine was also effective against severe disease.

8/

Even though the confidence interval was 46-94, the findings correlate with recent observations from England, Northern Ireland and Wales, where a 1st dose of vaccine appeared to be almost as effective as 2nd dose in preventing critical illness. Will link that tweet below.

9/

This fits the biological plausibility model - where T-cell library is created with the FIRST encounter, while a 2nd dose chiefly serves to amplify the antibody level using the principle of an anamnestic response.

Thus, chance of infection is low in the initial few months.

10/

This paper also cross references previous work that showed that 93% of CD4 and 97% of CD8T cell epitopes (recognisable parts) are conserved (unaffected by mutations) - ❗️EVEN IN VARIANTS.

In spite of mutations, there are conserved regions in the spike protein eg. S340-S365.

11/

In summary, the virus will never be able to completely evade our immune response, even though we will continue to see studies from laboratories that claim “reduction in neutralisation titres”, and scary pronouncements on mutations that threaten to “escape” our antibodies.

12/

The findings of the study correlate EXACTLY what we are seeing on the ground. A large number of doctors have consistently reported that the chance of getting severe disease is extremely rare among the vaccinated population, and also among previously infected people.

13/

Those who are new to immunology, technical papers & alarming tweets can lead to a sense of doom -which is far from the truth.

What the world needs is for people to receive 2 doses of vaccine ASAP, at least 1 dose for those with past infection to boost their antibody levels.

14/

We must also not forget that vaccination is only one of four pillars of preventing the pandemic.

Pandemic control is like a chair with four legs, the other three include wearing masks (particularly while indoors), improving room ventilation, and reducing indoor gatherings.

15/

What we see now is ignoring the other 3 legs - and focusing solely on vaccinations. This is the wrong strategy, and is also one of the reasons why even wealthy nations are not able to control it.

All 4 legs are equally important. Vaccination is not a substitute for NPI.

16/16

The effect of 1st dose vaccine in reducing severe disease (not infection) is worthy of more study. It is biologically plausible.

See thread above 👆 for context

https://twitter.com/RajeevJayadevan/status/1462330010123976707

@threadreaderapp please unroll