This work was performed as the starting point of a PhD for a very talented clinican scientist, Syandrez
Prima Putra, with some help from PhD student Selin Cankat

We hope this resource will be useful for those doing immune monitoring of HPV and for those designing vaccines to induce cross-reactive T cells.

We curate Epitopes by protein, HLA-restriction, and HPV type in supplementary tables.

This showed proof-of-concept that immunogenic cross-reactivity epitopes can be identified for inclusion in a pan-genotype vaccine and we have identified the regions where more epitope mapping is needed to realise this aim 👩🏽‍🔬

Filling the gaps In silico: With a curated list of HLA alleles and epitope prediction tools (NetMHC) we determined which known epitopes could be restricted by multiple HLA alleles (promiscuous) and are immunodominant (seen often in individuals of the right HLA type).

Filling the gaps In silico: We aligned 485 HPV reference sequences ⁑ (curated by PAVE: pave.niaid.nih.gov) and looked at conservation of known epitopes across types.

Some regions are so understudied 🫣there are just a handful, or even a single epitope described, such as for the conserved L2 protein. A clear research bias that if addressed could lead to the identification cross-reactive/protective T cell immunity.

Current Bias: Due to interest in T cells targeting oncogenic proteins E6/E7 in high-risk types ♋️and CD4 help to B cells making Abs to E1, there is clear bias in known epitopes

To start this work, Syandrez performed a meta-analysis of known epitopes 🖥️ (using the fantastic resource IEDB @iedb.bsky.social) and investigated what is already known about:
- viral proteome coverage 🧫
- HLA-restriction 🧬
- conservation of epitopes across types (high and low risk) 🌴

www.thelancet.com/journals/ebi...
#tcell #vaccineswork #immunology #vaccine

In vivo challenge after vaccination also showed strong protection for the i.n. administered vaccine, although protection wasn’t compared to the i.m. vaccine. Further evidence for targeting the local mucosa to facilitate protective immunity.

T cell repertoire analysis: www.thelancet.com/journals/ebi...

#tcell #vaccineswork #vaccine #clinicaltrial #immunology

Full phase 3 study: www.nejm.org/doi/full/10....

Lots of food for thought from these two studies.
1) It’s great to see comprehensive repertoire analysis being applied to clinical trial data
2) Could a bespoke T cell targeting vaccine have added benefit?
3) How does site of injection affect systemic vs local immune responses?

This follow-up used repertoire analysis and functional assays to show
1) T cells were only partially correlated with the protective immunity to SARS-CoV-2.
2) In those with breakthrough infection, T cell responses correlated with less severe symptoms.
A great analysis overall!