Thread by @VirusesImmunity

Here is a thread to explain the findings of this study, that used computational tools to predict T cell reactive sequences in #SARSCOV2 subunit vaccines.

The bottom line: there is no cause for alarm.

Here is why (1/n)

https://twitter.com/timkmak/status/1334872138579324932

Our adaptive immune system has 2 types of white blood cells known as lymphocytes. T cells and B cells. These lymphocytes give us protection from wide variety of pathogens. Each lymphocyte has unique receptor that detect specific features of a pathogen. (2/n)

B cells detect pathogens structures through antibodies. T cells cannot detect pathogens on their own. They can only “see” pathogen when tiny pieces of viral proteins (peptides) are presented by molecules called major histocompatibility complex (MHC). (3/n)

T cells that detect specific pathogen peptide on MHC become activated and functional. Humans carry multiple copies of MHC genes (thru polymorphism and polygeny). MHC genes are the most diverse set of genes in human genome. (4/n)

Some are called class I MHC, which present peptides to CD8 T cells (killer cells). Others are called class II MHC, which present peptides to CD4 T cells (helper cells).
Why are there so many types of MHC in the human genome? (5/n)

Well, there are infinite possible amino acid sequences that pathogens can have (due to diversity and mutation). Each MHC can only present peptide that contain specific amino acid motifs. If we relied on one MHC to present pathogen peptides,.. (6/n)

..humans will be vulnerable to infection by those pathogens that do not contain such peptide motifs. Frequencies of each type of MHC genes vary widely across the globe. (7/n)
frontiersin.org/articles/10.33…

Back to the study in question. The authors used computational modeling to predict peptides that are likely to be presented to T cells by MHC molecules in White, Black and Asian populations. (8/n)
cell.com/cell-systems/f…

Within just the receptor binding domain (RBD) of the spike protein (221 amino acid), 0.8% of White, and 37.3% of Asian had no predicted peptides that bind to their MHC class II proteins. However Moderna, Pfizer, AstraZeneca vaccines all use the full length S (1273 aa). (9/n)

Good news is that authors found that >99% of White, Black and Asian populations’ MHC class I can present at least 5 peptides from the Spike protein. On MHC class II, >98% of all people have at least 3 peptides predicted to be presented. (10/n)

What does this mean? That current leading vaccine candidates have the capacity to generate good T cell responses in diverse populations. T helper cells will also stimulate good antibody responses from B cells. (11/n)

The ultimate proof of vaccine-induced protection will become available when millions of people get vaccinated. Until then, there is little need to worry about Blacks and Asians not being protected by vaccines. All my figures were made by @BioRender. (End)