Syrian Hamster Model

CBER researchers were part of a worldwide effort to develop and characterize a small animal model to study SARS-CoV-2 evolution, pathogenesis, vaccination, and treatment.  Adult Syrian hamsters can be productively infected with SARS-CoV-2 and exhibit symptoms that resemble the disease in COVID-19 patients.  Importantly, hamsters are protected by vaccination. Additionally, infected hamsters transmit SARS-CoV-2 to other hamsters through close contact or by airborne droplets. Studies taking advantage of this model may help guide development of vaccines and treatments against COVID-19, as well as public health policies. [Selvaraj 2021 Publication | Stauft 2023 Publication]

CoCoPUTS

Released in 2019, CoCoPUTs contains codon usage, codon-pair usage, dinucleotide, junction dinucleotide, GC content, and effective number of codons (ENC) calculations for coding sequences derived from over one million species listed on GenBank or RefSeq databases. This resource represents significant advances on earlier codon usage databases in terms of scale (number of species) and scope (diversity of calculations). It has numerous applications towards the design of codon and codon-pair optimized therapeutics and gene therapies which require accurate knowledge of up-to-date codon and codon-pair usage information. [Tool Information | Tool | Alexaki 2019 Publication]

Tissue CoCoPUTS

Released in 2020, Tissue CoCoPUTs builds on the work of the original CoCoPUTs by combining earlier codon usage analyses with gene expression data from the Genotype-Tissue-Expression (GTEx) project. This resource presents all of the same statistics of CoCoPUTs at the level of 51 individual human tissues. This database has many applications including tissue-specific genetic engineering and development of genetic variant prediction tools, which help the agency respond to the growing demand for effective regulation of novel recombinant biologics. In the future, this data could also be combined with tRNA anticodon information to better understand the relationship between codon usage and tRNA abundance, which could be critical in determining translation kinetics and efficiency across tissues. [Tool Information | Tool | Kames 2020 Publication]

TcPro

This is a mathematical model that predicts the temporal dynamics of T cell counts in common ex vivo assays for drug immunogenicity. This tool provides rapid and inexpensive initial screens for new biotherapeutics and can be used to determine the potential immunogenicity risk of new sequences introduced while bioengineering proteins. TCPro was validated using an experimental immunogenicity dataset, making predictions on the population-based immunogenicity risk of 15 protein-based biotherapeutics. Immunogenicity rankings generated using TCPro are consistent with the reported clinical experience with these therapeutics. [Tool | Yogurtcu 2019 Publication]

SampPick

Immune responses are often HLA-restricted, and it is important that the distribution of HLA variants used in the immunogenicity assessments provides adequate coverage of the target population. Due to biases inherent to the collection of samples in a blood bank or donor pool, simple random sampling will not achieve a truly representative sample of the population of interest. Sampick optimizes cohort selection to closely match the frequency distribution of a target population or subpopulation. With inputs of a target background frequency distribution for a population and a set of available, HLA-typed donors, the algorithm will iteratively create a cohort of donors of a user selected size that will closely match the target population. [Tool | McGill 2019 Publication]

SARS-CoV-2 RNA Reference Panel

At the start of the Covid-19 pandemic, CBER and CDRH scientists engaged in a collaboration to prepare reference panels to evaluate the performance of tests for detection of SARS-CoV-2 RNA. The panels included different concentrations of heat-inactivated SARS-CoV-2 or related coronaviruses designed to challenge the sensitivity and specificity of Covid tests. Based on a protocol provided by FDA, manufacturers were asked to use their test to determine whether the reference panel samples were positive or negative for SARS-CoV-2 and return the results to FDA. The results allowed FDA to determine the limit of detection for each test. Data comparing the sensitivity of different tests were useful for healthcare providers and clinical laboratories during the Public Health Emergency. [FDA News Release | FDA News Release]