Evidence map›Paper›PMID 41911178›Full record

ArticlePloS one2026

Stirred tank bioreactor process for chikungunya vaccine candidate VEEV-ΔC-CHIKV.

Tong Chang, ChengLin Deng, LiXia Xie, YiFan Zheng, YaNan Zhang, JiaWei Liu, ZhenFang Fu, Bo Zhang, Qi An, DaYong Tian

Abstract read
In one paragraph

Article in PloS one, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

10 authors.

Tong ChangR&D Department, Shanghai King-Cell Biotechnology Co., Ltd., Shanghai, Shanghai, China.
ChengLin DengKey Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, China.
LiXia XieR&D Department, Shanghai King-Cell Biotechnology Co., Ltd., Shanghai, Shanghai, China.
YiFan ZhengR&D Department, Shanghai King-Cell Biotechnology Co., Ltd., Shanghai, Shanghai, China.
YaNan ZhangKey Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, China.
JiaWei LiuR&D Department, Shanghai King-Cell Biotechnology Co., Ltd., Shanghai, Shanghai, China.
ZhenFang FuR&D Department, Shanghai King-Cell Biotechnology Co., Ltd., Shanghai, Shanghai, China.
Bo ZhangKey Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, China.
Qi AnR&D Department, Shanghai King-Cell Biotechnology Co., Ltd., Shanghai, Shanghai, China.
DaYong TianR&D Department, Shanghai King-Cell Biotechnology Co., Ltd., Shanghai, Shanghai, China.ORCID https://orcid.org/0000-0001-8978-8970

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Chikungunya virus (CHIKV), a mosquito-borne alphavirus with significant public health impact, has caused recurrent epidemics across Africa, Asia, and the Americas. Despite the recent approval of a live-attenuated vaccine (Chix), scalable manufacturing processes for CHIKV vaccines remain critical to meet global demand. In this context, we previously constructed a chimeric virus, VEEV-ΔC-CHIKV, by replacing the backbone of ΔC-CHIKV with that of the VEEV replicon while retaining the CHIKV antigenic glycoprotein (E3-E2-6K-E1). A series of experiments have demonstrated that the chimeric virus exhibits safety, stability, and immunogenicity, making it a promising candidate for a new attenuated live vaccine strain. Therefore, to further validate its viral properties and explore the potential for large-scale production, we developed an optimized bioreactor-based production process for VEEV-ΔC-CHIKV. Utilizing adherent Vero cells in mechanically stirred bioreactors, we systematically optimized key parameters, including carrier type selection, cell seeding density, human albumin supplementation, and nutrient modulation, to maximize viral titers while minimizing the accumulation of metabolic byproducts. Results indicated that Cytodex™ 1 microcarriers outperformed Fibra-Cel carriers, enabling 10 consecutive harvests with viral titers ≥ 105 PFU/mL (compared to 4 harvests for Fibra-Cel). When the initial cell density was 6.5 × 105 cells/mL, the total virus yield was 77% higher than at a cell density of 2.5 × 105 cells/mL. Adding 1.0% human albumin doubled total virus production compared to the addition of 0.5%. Nutrient modulation through the maintenance of glucose (>3 g/L) and glutamine (>0.5 g/L) in fed-batch systems enhanced peak titers to 106.4 PFU/mL, representing a 2.2-fold increase compared to non-fed controls. This study establishes a scalable and cost-effective bioreactor platform for the production of the CHIKV vaccine, highlighting the critical interplay between nutrient optimization and viral yield enhancement, while emphasizing the advantages of automated process control in bioreactors to facilitate large-scale, high-yield viral production.

Indexed as

BioreactorsChikungunya FeverChikungunya virusViral VaccinesAnimalsChlorocebus aethiopsHumansVaccines, AttenuatedVero CellsChikungunya vaccineVaccines, AttenuatedViral Vaccines

Identifiers

PMID41911178
PMCPMC13035149

What Socratic 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 Socratic graph.