Thread by @vipintukur

If you do want to read ONE paper/study this weekend, please go through this 🧵on an amazing work done by @BoytonRosemary @Daltmann10 & colleagues that has shaken the entire academic world! See the link👇 1/

When the process of developing new COVID19 vaccines started in 2020, the two threats to their success that most vaccine experts feared were: Antibody Driven Enhancement (ADE) and Original antigenic sin aka Antigenic Imprinting 2/

sciencedirect.com/science/articl…

Fortunately, the first immune phenomenon (#ADE) that had marred the reputation of one Dengue vaccine and few candidates ag RSV & others, is yet to be observed with current Covid vaccines. 3/

However, the ghost of #OAS has come to haunt the vaccine experts after the advent of #Omicron. And a huge question mark is put in-front of immunity gained either through natural infection or vaccination. 4/

pubmed.ncbi.nlm.nih.gov/34185632/

Ever wonder why there are so many Omicron breakthrough infections, even among people who have been triple vaccinated? How this is affected by previous infection history? And whether Omicron infection at least offers a ‘natural booster’ of COVID-19 immunity? 5/

In January, 2022, a study in Cell by #KatharinaRöltgen & colleagues first hinted toward existence of Antigenic imprinting. They concluded that imprinting from initial antigen exposures alters IgG responses to viral variants 6/

cell.com/cell/fulltext/…

A new study in Science has shaken the academia globally! The team from @imperialcollege analysed blood samples from UK’s HCWs who recd 3 doses of mRNA vax & who had different SARS2 infection histories, to investigate Ab, T & B cell immunity ag Omicron 7/

They found people with no prior SARS2 infection who then had Omicron showed enhanced cross-reactive immunity to previous variants – w/ enhanced B & T cell immunity against Alpha, Beta, Gamma & Delta – but they showed a reduced boosting against the Omicron spike protein itself 8/

HCWs with prior #Alpha infection showed a less sustained antibody response against Omicron. 9/

People infected during the first wave of the pandemic and then again with Omicron lacked any immune boosting, in an effect the researchers termed ‘hybrid immune damping’. 10/

The impact of immune imprinting means that after infection with Omicron people who had previously been infected during the first wave are not immune boosted against a subsequent infection with the variant, and potentially its subvariants BA.4 & BA.5. 11/

They highlight that while vaccination provides protection against severe disease, the impact of infection and re-infection on long term health, including long COVID, is not known. The current study only focused on triple mRNA vaccinated individuals. 12/

Now, let’s summarise the key takeaways of the above study

1-The link between a person’s infection history and their response to the vaccine is now clear.

2-Previous infection with different variants impacts both the potency and durability of your immune responses. 13/

3-The effectiveness of current vaccination strategies will depend not only on which variants become dominant in the future, but also on how previous waves of infection have impacted our immunity. 14/

4-‘Hybrid immune damping’ is a new phenomenon: infection with the ancestral strain impairs the boosting effect of a subsequent Omicron infection. 15/

5-The broad diversity of infection history in our population means that further exposure to the current vaccine has different implications for different people. 16/

The results in a layman’s term:
If you had original Covid, your immune system will not learn anything new from an Omicron infection. Your body will not learn to make Abs or T-cells to new variant & instead still relies on the old response due to immune memory & imprinting 17/

Now, with such diverse patterns of SARS2 infection & vaccination across different global populations, it is more important than ever to understand the immune impacts of these patterns and how they might shape immunity to future variants. 18/

This study shows that an individual’s vaccination & infection history can have a huge bearing on their immune response to variants, including to Omicron. 19/

What could be the most concerning issue?

Omicron could potentially mutate further into a more pathogenic strain or become better able to overcome vaccine protection. 20/

In this scenario, people who have had Omicron infection would be poorly boosted against future infection depending on their immune imprinting

21/

imperial.ac.uk/news/237315/om…