pVACtools v6 significantly expands neoantigen prediction, visualization, and personalized cancer vaccine design capabilities

Identifying and prioritizing tumor-specific neoantigens is critical for advancing cancer immunotherapy, particularly checkpoint blockade therapies and neoantigen-based vaccines. Current standard-of-care often faces resistance, necessitating more precise, personalized approaches. Neoantigens, unique to tumor cells, represent ideal targets for activating the host immune system, but their accurate prediction and selection remain a significant computational challenge. Robust bioinformatics tools are essential to bridge this gap, enabling the design of effective, antigen-specific T-cell responses.

The developers of pVACtools describe eight major advances to their open-source informatic suite, initially released in 2016. These updates include expanded features for neoantigen quality and safety assessment, such as peptide presentation scoring and immunogenicity prediction. New modules were added: pVACsplice for cis-splicing mutation neoantigens and pVACbind for noncanonical sources. The pVACvector algorithm was substantially improved for DNA/mRNA vaccine design, and new utilities support synthetic long peptide vaccine design. The suite also extended prediction support for many non-human species and introduced pVACcompare for result comparison.

The updated pVACtools v6 now offers expanded neoantigen quality and safety assessment features, including support for peptide presentation scoring, immunogenicity prediction, anchor residue analysis, reference proteome similarity, and percentile score calculation. A new tool, pVACsplice, was added for predicting neoantigens from tumor-specific cis-splicing mutations, alongside pVACbind for flexible support of noncanonical neoantigen sources. Neoantigen selection strategies were improved, and the pVACvector algorithm achieved > higher DNA/mRNA vector vaccine design success rates with shorter runtimes. New utilities were also integrated to support synthetic long peptide vaccine design, extending prediction capabilities to many non-human species, and pVACcompare was added for comparing pVACseq results. These updates collectively reinforce pVACtools as the field's most comprehensive toolkit for neoantigen research.