Evidence map›Paper›PMID 31400346›Full record

ArticleJournal of pharmaceutical sciences2020

Characterizing and Minimizing Aggregation and Particle Formation of Three Recombinant Fusion-Protein Bulk Antigens for Use in a Candidate Trivalent Rotavirus Vaccine.

Sanjeev Agarwal, Neha Sahni, John M Hickey, George A Robertson, Robert Sitrin, Stanley Cryz, Sangeeta B Joshi, David B Volkin

Open access · hybridAbstract read
In one paragraph

Article in Journal of pharmaceutical sciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.4field-weighted citation impact, top 19% 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, 16 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

Sanjeev AgarwalDepartment of Pharmaceutical Chemistry, Vaccine Analytics and Formulation Center, University of Kansas, 2030 Becker Drive, Lawrence, Kansas 66047.
Neha SahniDepartment of Pharmaceutical Chemistry, Vaccine Analytics and Formulation Center, University of Kansas, 2030 Becker Drive, Lawrence, Kansas 66047.
John M HickeyDepartment of Pharmaceutical Chemistry, Vaccine Analytics and Formulation Center, University of Kansas, 2030 Becker Drive, Lawrence, Kansas 66047.
George A RobertsonThe Center for Vaccine Innovation and Access, PATH, 455 Massachusetts Avenue NW Suite 1000, Washington, District of Columbia 20001.
Robert SitrinThe Center for Vaccine Innovation and Access, PATH, 455 Massachusetts Avenue NW Suite 1000, Washington, District of Columbia 20001.
Stanley CryzThe Center for Vaccine Innovation and Access, PATH, 455 Massachusetts Avenue NW Suite 1000, Washington, District of Columbia 20001.
Sangeeta B JoshiDepartment of Pharmaceutical Chemistry, Vaccine Analytics and Formulation Center, University of Kansas, 2030 Becker Drive, Lawrence, Kansas 66047.
David B VolkinDepartment of Pharmaceutical Chemistry, Vaccine Analytics and Formulation Center, University of Kansas, 2030 Becker Drive, Lawrence, Kansas 66047. Electronic address: volkin@ku.edu.
University of Kansas · USProgram for Appropriate Technology in Health · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

In a companion paper, the structural integrity, conformational stability, and degradation mechanisms of 3 recombinant fusion-protein antigens comprising a non-replicating rotavirus (NRRV) vaccine candidate (currently being evaluated in early-stage clinical trials) are described. In this work, we focus on the aggregation propensity of the 3 NRRV antigens coupled to formulation development studies to identify common frozen bulk candidate formulations. The P2-VP8-P[8] antigen was most susceptible to shaking and freeze-thaw-induced aggregation and particle formation. Each NRRV antigen formed aggregates with structurally altered protein (with exposed apolar regions and intermolecular β-sheet) and dimers containing a non-native disulfide bond. From excipient screening studies with P2-VP8-P[8], sugars or polyols (e.g., sucrose, trehalose, mannitol, sorbitol) and various detergents (e.g., Pluronic F-68, polysorbate 20 and 80, PEG-3350) were identified as stabilizers against aggregation. By combining promising additives, candidate bulk formulations were optimized to not only minimize agitation-induced aggregation, but also particle formation due to freeze-thaw stress of P2-VP8-P[8] antigen. Owing to limited material availability, stabilization of the P2-VP8-P[4] and P2-VP8-P[6] was confirmed with the lead candidate P2-VP8-P[8] formulations. The optimization of these bulk NRRV candidate formulations is discussed in the context of subsequent drug product formulations in the presence of aluminum adjuvants.

Indexed as

Protein AggregatesAntigens, ViralDrug CompoundingDrugs, InvestigationalDrug StabilityDrug StorageExcipientsFreezingParticle SizeProtein StabilityRecombinant Fusion ProteinsRotavirus VaccinesVaccines, SubunitAntigens, ViralDrugs, InvestigationalExcipientsProtein AggregatesRecombinant Fusion ProteinsRotavirus VaccinesVaccines, Subunitaggregationformulationrecombinant proteinrotavirusstabilitysubunit vaccine

Identifiers

PMID31400346
PMCPMC6941221
OpenAlexW2965383111

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.