This repo aims to design "cocktail" vaccines of several SARS-CoV-2 spikes that include both a current leading variant (XBB.1.16) and some designed sequences with possible "future" RBD mutations The design are made by Jesse Bloom.
The future variants are designed by picking mutations that:
- are expected to cause a lot of antigenic escape using the escape calculator
- have relatively favorable affects on ACE2 affinity and RBD expression as measured using deep mutational scanning
- are estimated to have favorable effects on viral fitness based on analysis of natural sequences
The configuration for the design is in config.yaml.
To make the designs, build the conda environment in environment.yml, and then run the Jupyter notebook design_vax.ipynb, which does the design.
The results designs are in the following files. If just one cocktail is being tested, we suggeset the one named cocktail-vax, but also provide designs for more aggressive cocktail (more mutations per spike) and a more conservative cocktail (fewer mutations per spike) as options.
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vax_designs/parent-vax.fa: the parent cocktail that just includes the XBB.1.16 sequence.
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vax_designs/cocktail-vax.fa: the cocktail that contains XBB.1.16 parent and designed mutants. There are ten candidate sequences listed here, and they are listed in the order they should be chosen for inclusion in a cocktail. For instance, if you just include five sequences take the first five.
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vax_designs/aggressive-cocktail-vax.fa: a more aggressive cocktail with a higher number of mutations per variant.
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vax_designs/conservative-cocktail-vax.fa: a more conservative cocktail with a lower number of mutations per variant.
The following points should be taken into consideration before starting any experiments:
- The designed sequences in the aforementioned files are spikes that do not contain any stabilizing mutations. For actual vaccine constructs, it may be desirable to add 2P or (preferably) 6P mutations to stabilize the pre-fusion spike.
- The spikes have not been validated for proper folding or expression, which should be done prior to beginning any vaccination experiments.
- The idea that these cocktail vaccines would be preferable or even non-inferior to a monovalent vaccine is untested and may not be true.