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Fulltext Engineering a stable CHO cell line for the expression of a MERS-coronavirus vaccine antigen

Nyon MP, Du L, Tseng CK, Seid CA, Pollet J, Naceanceno KS, et al.

Vaccine, 2018 03 27;36(14):1853-1862.
PMID: 29496347 DOI: 10.1016/j.vaccine.2018.02.065

Middle East respiratory syndrome coronavirus (MERS-CoV) has infected at least 2040 patients and caused 712 deaths since its first appearance in 2012, yet neither pathogen-specific therapeutics nor approved vaccines are available. To address this need, we are developing a subunit recombinant protein vaccine comprising residues 377-588 of the MERS-CoV spike protein receptor-binding domain (RBD), which, when formulated with the AddaVax adjuvant, it induces a significant neutralizing antibody response and protection against MERS-CoV challenge in vaccinated animals. To prepare for the manufacture and first-in-human testing of the vaccine, we have developed a process to stably produce the recombinant MERS S377-588 protein in Chinese hamster ovary (CHO) cells. To accomplish this, we transfected an adherent dihydrofolate reductase-deficient CHO cell line (adCHO) with a plasmid encoding S377-588 fused with the human IgG Fc fragment (S377-588-Fc). We then demonstrated the interleukin-2 signal peptide-directed secretion of the recombinant protein into extracellular milieu. Using a gradually increasing methotrexate (MTX) concentration to 5 μM, we increased protein yield by a factor of 40. The adCHO-expressed S377-588-Fc recombinant protein demonstrated functionality and binding specificity identical to those of the protein from transiently transfected HEK293T cells. In addition, hCD26/dipeptidyl peptidase-4 (DPP4) transgenic mice vaccinated with AddaVax-adjuvanted S377-588-Fc could produce neutralizing antibodies against MERS-CoV and survived for at least 21 days after challenge with live MERS-CoV with no evidence of immunological toxicity or eosinophilic immune enhancement. To prepare for large scale-manufacture of the vaccine antigen, we have further developed a high-yield monoclonal suspension CHO cell line.
Fulltext Cochrane Rehabilitation: report of the first year of work

Negrini S, Arienti C, Pollet J, Engkasan JP, Gimigliano F, Grubisic F, et al.

Eur J Phys Rehabil Med, 2018 Jun;54(3):463-465.
PMID: 29901359 DOI: 10.23736/S1973-9087.18.05317-0

Since his launch Cochrane Rehabilitation has started working to be a bridge between Cochrane and rehabilitation. After a fist period of work organization, the field has started producing actions through its committees: communication, education, methodology, publication and reviews. All the results of this first year of activity are listed in this report.
Clinical replicability of rehabilitation interventions in randomized controlled trials reported in main journals is inadequate

Negrini S, Arienti C, Pollet J, Engkasan JP, Francisco GE, Frontera WR, et al.

J Clin Epidemiol, 2019 10;114:108-117.
PMID: 31220570 DOI: 10.1016/j.jclinepi.2019.06.008

OBJECTIVE: The objective of this study was to study if randomized controlled trials (RCTs) in rehabilitation (a field where complex interventions prevail) published in main journals include all the details needed to replicate the intervention in clinical practice (clinical replicability).
STUDY DESIGN AND SETTING: Forty-seven rehabilitation clinicians of 5 professions from 7 teams (Belgium, Italy, Malaysia, Pakistan, Poland, Puerto Rico, the USA) reviewed 76 RCTs published by main rehabilitation journals exploring 14 domains chosen through consensus and piloting.
RESULTS: The response rate was 99%. Inter-rater agreement was moderate/good. All clinicians considered unanimously 12 (16%) RCTs clinically replicable and none not replicable. At least one "absent" information was found by all participants in 60 RCTs (79%), and by a minimum of 85% in the remaining 16 (21%). Information considered to be less well described (8-19% "perfect" information) included two providers (skills, experience) and two delivery (cautions, relationships) items. The best described (50-79% "perfect") were the classic methodological items included in CONSORT (descending order: participants, materials, procedures, setting, and intervention).
CONCLUSION: Clinical replicability must be considered in RCTs reporting, particularly for complex interventions. Classical methodological checklists such as CONSORT are not enough, and also Template for Intervention Description and Clinical replication do not cover all the requirements. This study supports the need for field-specific checklists.
Fulltext Cochrane Rehabilitation: 2019 annual report

Arienti C, Kiekens C, Bettinsoli R, Engkasan JP, Gimigliano F, Grubisic F, et al.

Eur J Phys Rehabil Med, 2020 Feb;56(1):120-125.
PMID: 32093464 DOI: 10.23736/S1973-9087.20.06188-2

During its third year of existence, Cochrane Rehabilitation goals included to point out the main methodological issues in rehabilitation research, and to increase the Knowledge Translation activities. This has been performed through its committees and specific projects. In 2019, Cochrane Rehabilitation worked on five different special projects at different stages of development: 1) a collaboration with the World Health Organization to extract the best evidence for Rehabilitation (Be4rehab); 2) the development of a reporting checklist for Randomised Controlled Trials in rehabilitation (RCTRACK); 3) the definition of what is the rehabilitation for research purposes; 4) the ebook project; and 5) a prioritization exercise for Cochrane Reviews production. The Review Committee finalized the screening and "tagging" of all rehabilitation reviews in the Cochrane library; the Publication Committee increased the number of international journals with which publish Cochrane Corners; the Education Committee continued performing educational activities such as workshops in different meetings; the Methodology Committee performed the second Cochrane Rehabilitation Methodological Meeting and published many papers; the Communication Committee spread the rehabilitation evidence through different channels and translated the contents in different languages. The collaboration with several National and International Rehabilitation Scientific Societies, Universities, Hospitals, Research Centers and other organizations keeps on growing.
Fulltext Cochrane Rehabilitation: 2018 annual report

Negrini S, Arienti C, Engkasan JP, Gimigliano F, Grubisic F, Howe T, et al.

Eur J Phys Rehabil Med, 2019 Apr;55(2):314-318.
PMID: 30938139 DOI: 10.23736/S1973-9087.19.05785-X

During its second year of existence, Cochrane Rehabilitation worked hard to accomplish new and old goals. The Review Committee completed the massive task of identifying and "tagging" all rehabilitation reviews in the Cochrane library. The Publication Committee signed agreements with several international journals and started the publication of Cochrane Corners. The Education Committee performed educational activities such as workshops in International Meetings. The Methodology Committee has completed a two days Cochrane Rehabilitation Methodological Meeting in Paris of which the results will soon be published. The Communication Committee reaches almost 5,000 rehabilitation professionals through social media, and is working on the translation of contents in Italian, Spanish, French, Dutch, Croatian and Japanese. Memoranda of Understanding have been signed with several National and International Rehabilitation Scientific Societies, Universities, Hospitals, Research Centres and other organizations. The be4rehab (best evidence for rehabilitation) project has been started with the World Health Organisation (WHO) to extract from Cochrane reviews and clinical guidelines the best currently available evidence to produce the WHO Minimum Package of Rehabilitation Interventions. The Cochrane Rehabilitation ebook is under development as well as a priority setting exercise with 39 countries from all continents.