Technologies for early detection of variants of interest
AssigneesBioNTech SE, InstaDeep Ltd
InventorsAlexander Muik, Asaf Poran, Yunpeng Liu, Ugur Sahin, Karim Beguir, Marcin Skwark, Thomas Pierrot, Yunguan Fu
Life of this patent
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Abstract
The present disclosure provides technologies for identifying, characterizing, and/or monitoring sequences of a variant of a reference infectious agent (e.g., but not limited to viral variants, for example in some embodiments SARS-CoV-2 variants) for transmissibility factors and/or immune escape potential, and/or for detecting and/or monitoring variants in environmental or biological samples, and/or for designing, preparing, and/or administering vaccines for such variants.
Claims31
A method for assessing risk for a variant polypeptide, the method comprising:
- providing an amino acid sequence of the variant polypeptide, which comprises one or more amino acid modifications relative to one or more reference viral polypeptides;
- modeling, utilizing a processing unit of a computing infrastructure, one or more structural features of the variant polypeptide that are involved in viral invasion of a host;
- determining, by the processing unit, based on sequence data associated with the viral polypeptide, distance of each of the one or more amino acid modifications relative to corresponding amino acids in the one or more the reference viral polypeptides;
- and
- designating, by the processing unit, the variant polypeptide as a variant with elevated risk when the variant polypeptide is characterized in that:
- it has an immune escape score that (i) satisfies a pre-determined immune escape threshold indicating likelihood of the variant polypeptide to be detected and neutralized by antibodies;
- and/or (ii) is ranked higher than at least one or more other variant polypeptides and/or reference viral polypeptides.
A method for assessing risk for a plurality of variant polypeptides, the method comprising:
- providing a plurality of amino acid sequences of the variant polypeptides, wherein each of the variant polypeptides comprises one or more amino acid modifications relative to one or more reference viral polypeptides;
- ascertaining, utilizing a processing unit of a computing infrastructure, for each of the variant polypeptides, an immune escape score by performing the following processes:
- modeling one or more structural features of each variant polypeptide that are involved in viral invasion of a host;
- determining, based on sequence data associated with the viral polypeptide, distance of each of the one or more amino acid modifications relative to the corresponding amino acids in the one or more reference viral polypeptides;
- ranking, by the processing unit, risk of the variant polypeptides in the plurality by referencing respective immune escape scores;
- and
- designating, by the processing unit, a variant polypeptide as a variant polypeptide with elevated risk when its immune escape score is ranked higher than that of at least one other variant polypeptide in the plurality.
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21-37. (canceled)
A method of producing a vaccine against SARS-CoV-2, the method comprising:
- identifying at least one variant polypeptide as a variant polypeptide of interest by:
- providing an amino acid sequence of the variant polypeptide, wherein the variant polypeptide comprises one or more amino acid modifications relative to one or more reference viral polypeptides;
- determining, utilizing a processing unit of a computing infrastructure, an immune escape score for the variant polypeptide by:
- modeling one or more structural features of the variant polypeptide that are involved in viral invasion of a host;
- and
- determining, based on sequence data associated with the viral polypeptide, distance of each of the one or more amino acid modifications relative to corresponding amino acids in the one or more reference viral polypeptides;
- and
- designating, by the processing unit, the variant polypeptide as the at least one variant polypeptide of interest based at least in part on the immune escape score;
- and
- producing, within no more than 1 month from the identification of the at least one variant polypeptide of interest, a vaccine comprising a polypeptide or a nucleic acid encoding the polypeptide, wherein the polypeptide comprises the at least one variant polypeptide of interest or immunogenic fragment thereof.
39-41. (canceled)
A SARS-CoV-2 Spike polypeptide or an immunogenic fragment or variant thereof, or a nucleic acid comprising a sequence encoding the same, wherein the Spike polypeptide or the immunogenic fragment or variant is determined as a variant of concern by:
- providing an amino acid sequence of the Spike polypeptide or the immunogenic fragment or variant, said Spike polypeptide or immunogenic fragment or variant thereof comprising one or more amino acid modifications relative to one or more reference viral polypeptides;
- determining, utilizing a processing unit of a computing infrastructure, an immune escape score for the Spike polypeptide or the immunogenic fragment or variant by:
- modeling one or more structural features of the Spike polypeptide or the immunogenic fragment or variant that are involved in viral invasion of a host;
- and
- determining, based on sequence data associated with the Spike polypeptide or the immunogenic fragment or variant, a distance of each of the one or more amino acid modifications relative to corresponding amino acids in the one or more reference viral polypeptides;
- and
- designating, by the processing unit, the Spike polypeptide or the immunogenic fragment or variant as a variant of concern based at least in part on the immune escape score.
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Dependencies are inferred from the claim text.