Biology subjects

Pattijn, S.

Publications and source records attributed to Pattijn, S..

3 recordsLinked to original sources

bioRxiv2025

The Immunogenicity Database Collaborative (IDC): A Standardized, Publicly Available Database for Clinical Immunogenicity Observations and Insights

The incidence and impact of anti-drug antibodies (ADAs) against biotherapeutics remain difficult to predict, limiting efforts to mitigate immunogenicity risk prior to clinical trials. Existing data are fragmented across disparate sources with inconsistent definitions, representing a key barrier to progress in the field. Here, we present the Immunogenicity Database Collaborative (IDC) and its release of the Immunogenicity Database (DB) V1: a structured clinical immunogenicity dataset integrating therapeutic characteristics, sequence, and patient cohort-level data from publicly available sources. The dataset includes 4,146 ADA datapoints, 1,788 cohorts, 727 clinical trials and 218 therapeutics. We highlight trends in ADA incidence, evaluate sources of variability, and identify driving factors of immunogenicity risk. This work provides a foundational resource to standardize and support immunogenicity risk assessment across the industry. It also provides an initial data architecture and invites the research community to contribute towards future expansions of the database into key areas of interest to the field.

pharmacology and toxicology↗

bioRxiv2021

The mutational landscape of SARS-CoV-2 variants diversifies T cell targets in an HLA supertype-dependent manner

The rapid, global dispersion of SARS-CoV-2 since its initial identification in December 2019 has led to the emergence of a diverse range of variants. The initial concerns regarding the virus were quickly compounded with concerns relating to the impact of its mutated forms on viral infectivity, pathogenicity and immunogenicity. To address the latter, we seek to understand how the mutational landscape of SARS-CoV-2 has shaped HLA-restricted T cell immunity at the population level during the first year of the pandemic, before mass vaccination. We analyzed a total of 330,246 high quality SARS-CoV-2 genome assemblies sampled across 143 countries and all major continents. Strikingly, we found that specific mutational patterns in SARS-CoV-2 diversify T cell epitopes in an HLA supertype-dependent manner. In fact, we observed that proline residues are preferentially removed from the proteome of prevalent mutants, leading to a predicted global loss of SARS-CoV-2 T cell epitopes in individuals expressing HLA-B alleles of the B7 supertype family. In addition, we show that this predicted global loss of epitopes is largely driven by a dominant C-to-U mutation type at the RNA level. These results indicate that B7 supertype-associated epitopes, including the most immunodominant ones, were more likely to escape CD8+ T cell immunosurveillance during the first year of the pandemic. Together, our study lays the foundation to help understand how SARS-CoV-2 mutants shape the repertoire of T cell targets and T cell immunity across human populations. The proposed theoretical framework has implications in viral evolution, disease severity, vaccine resistance and herd immunity.

immunology↗

bioRxiv2020

Peptide vaccine candidate mimics the heterogeneity of natural SARS-CoV-2 immunity in convalescent humans and induces broad T cell responses in mice models

We developed a global peptide vaccine against SARS-CoV-2 that addresses the dual challenges of heterogeneity in the immune responses of different individuals and potential heterogeneity of the infecting virus. PolyPEPI-SCoV-2 is a polypeptide vaccine containing nine 30-mer peptides derived from all four major structural proteins of the SARS-CoV-2. Vaccine peptides were selected based on their frequency as HLA class I and class II personal epitopes (PEPIs) restricted to multiple autologous HLA alleles of individuals in an in silico cohort of 433 subjects of different ethnicities. PolyPEPI-SCoV-2 vaccine administered with Montanide ISA 51VG adjuvant generated robust, Th1-biased CD8+ and CD4+ T cell responses against all four structural proteins of the virus, as well as binding antibodies upon subcutaneous injection into BALB/c and CD34+ transgenic mice. In addition, PolyPEPI-SCoV-2-specific, polyfunctional CD8+ and CD4+ T cells were detected ex vivo in each of the 17 asymptomatic/mild COVID-19 convalescents blood investigated, 1-5 months after symptom onset. The PolyPEPI-SCoV-2-specific T cell repertoire used for recovery from COVID-19 was extremely diverse: donors had an average of seven different peptide-specific T cells, against the SARS-CoV-2 proteins; 87% of donors had multiple targets against at least three SARS-CoV-2 proteins and 53% against all four. In addition, PEPIs determined based on the complete HLA class I genotype of the convalescent donors were validated, with 84% accuracy, to predict PEPI-specific CD8+ T cell responses measured for the individuals. Extrapolation of the above findings to a US bone marrow donor cohort of 16,000 HLA-genotyped individuals with 16 different ethnicities (n=1,000 each ethnic group) suggest that PolyPEPI-SCoV-2 vaccination in a general population will likely elicit broad, multi-antigenic CD8+ and CD4+ T cell responses in 98% of individuals, independent of ethnicity, including Black, Asian, and Minority Ethnic (BAME) cohorts.

immunology↗