Evidence map›Paper›PMID 33285182›Full record

ArticleJournal of pharmaceutical sciences2021

Rapid Developability Assessments to Formulate Recombinant Protein Antigens as Stable, Low-Cost, Multi-Dose Vaccine Candidates: Case-Study With Non-Replicating Rotavirus (NRRV) Vaccine Antigens.

Nishant Sawant, Kawaljit Kaur, David A Holland, John M Hickey, Sanjeev Agarwal, Joseph R Brady, Neil C Dalvie, Mary Kate Tracey, M Lourdes Velez-Suberbie, Stephen A Morris and 7 more

Erratum issuedOpen access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of pharmaceutical sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
0.4field-weighted citation impact, top 26% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed, 21 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors at 3 institutions in 2 countries.

Nishant SawantDepartment of Pharmaceutical Chemistry, Vaccine Analytics and Formulation Center, University of Kansas, 2030 Becker Drive, Lawrence, KS 66047, USA.
Kawaljit KaurDepartment of Pharmaceutical Chemistry, Vaccine Analytics and Formulation Center, University of Kansas, 2030 Becker Drive, Lawrence, KS 66047, USA.
David A HollandDepartment of Pharmaceutical Chemistry, Vaccine Analytics and Formulation Center, University of Kansas, 2030 Becker Drive, Lawrence, KS 66047, USA.
John M HickeyDepartment of Pharmaceutical Chemistry, Vaccine Analytics and Formulation Center, University of Kansas, 2030 Becker Drive, Lawrence, KS 66047, USA.
Sanjeev AgarwalDepartment of Pharmaceutical Chemistry, Vaccine Analytics and Formulation Center, University of Kansas, 2030 Becker Drive, Lawrence, KS 66047, USA.
Joseph R BradyDepartment of Chemical Engineering, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Neil C DalvieDepartment of Chemical Engineering, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Mary Kate TraceyDepartment of Chemical Engineering, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
M Lourdes Velez-SuberbieDepartment of Biochemical Engineering, University College London, Bernard Katz Building, Gower Street, London WC1E 6BT, UK.
Stephen A MorrisDepartment of Biochemical Engineering, University College London, Bernard Katz Building, Gower Street, London WC1E 6BT, UK.
Shaleem I JacobDepartment of Biochemical Engineering, University College London, Bernard Katz Building, Gower Street, London WC1E 6BT, UK.
Daniel G BracewellDepartment of Biochemical Engineering, University College London, Bernard Katz Building, Gower Street, London WC1E 6BT, UK.
Tarit K MukhopadhyayDepartment of Biochemical Engineering, University College London, Bernard Katz Building, Gower Street, London WC1E 6BT, UK.
Kerry R LoveDepartment of Chemical Engineering, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
J Christopher LoveDepartment of Chemical Engineering, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Sangeeta B JoshiDepartment of Pharmaceutical Chemistry, Vaccine Analytics and Formulation Center, University of Kansas, 2030 Becker Drive, Lawrence, KS 66047, USA.
David B VolkinDepartment of Pharmaceutical Chemistry, Vaccine Analytics and Formulation Center, University of Kansas, 2030 Becker Drive, Lawrence, KS 66047, USA. Electronic address: volkin@ku.edu.
University of Kansas · USMassachusetts Institute of Technology · USUniversity College London · GB

Funding

VIRUS PRODUCTION COREP30CA014051 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI Paula T Hammond · 1985 to 2026
$93.9M
NCI NIH HHS P30 CA014051
6 · The paper itself

Abstract

A two-step developability assessment workflow is described to screen variants of recombinant protein antigens under various formulation conditions to rapidly identify stable, aluminum-adjuvanted, multi-dose vaccine candidates. For proof-of-concept, a series of sequence variants of the recombinant non-replicating rotavirus (NRRV) P[8] protein antigen (produced in Komagataella phaffii) were compared in terms of primary structure, post-translational modifications, antibody binding, conformational stability, relative solubility and preservative compatibility. Based on these results, promising P[8] variants were down-selected and the impact of key formulation conditions on storage stability was examined (e.g., presence or absence of the aluminum-adjuvant Alhydrogel and the preservative thimerosal) as measured by differential scanning calorimetry (DSC) and antibody binding assays. Good correlations between rapidly-generated developability screening data and storage stability profiles (12 weeks at various temperatures) were observed for aluminum-adsorbed P[8] antigens. These findings were extended and confirmed using variants of a second NRRV antigen, P[4]. These case-study results with P[8] and P[4] NRRV variants are discussed in terms of using this vaccine formulation developability workflow to better inform and optimize formulation design with a wide variety of recombinant protein antigens, with the long-term goal of rapidly and cost-efficiently identifying low-cost vaccine formulations for use in low and middle income countries.

Indexed as

RotavirusRotavirus VaccinesAntigensRecombinant ProteinsSaccharomycetalesAntigensRecombinant ProteinsRotavirus VaccinesDevelopabilityFormulationMulti-dosePreservativeRotavirusStabilityVaccine

Identifiers

PMID33285182
PMCPMC7884052
OpenAlexW3113133140

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.