{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T14:12:15Z","timestamp":1771596735406,"version":"3.50.1"},"reference-count":36,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T00:00:00Z","timestamp":1771545600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"State of S\u00e3o Paulo Research Foundation (FAPESP) S\u00e3o Paulo, Brazil","award":["2007\/50082-2"],"award-info":[{"award-number":["2007\/50082-2"]}]},{"name":"Butantan Foundation and Foundation for Administration Development"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Bioengineering"],"abstract":"<jats:p>Haemophilus influenzae b (Hib) is a pathogenic bacterium that causes meningitis worldwide, mainly in children less than two years old. The capsular polysaccharide b (PRP) is an essential antigen for vaccine formulation. This study aimed to develop a high-yield, technically accessible production strategy for PRP production to facilitate vaccine manufacturing in non-profit laboratories. Various fed-batch cultivation strategies were evaluated to address metabolic limitations and identify a robust, simplified process suitable for seamless scale-up to pilot scale. Glucose limitation strategies did not reduce inhibitory acetic acid accumulation due to deficiencies in Hib\u2019s respiratory chain, whereas oxygen availability was identified as critical parameter. Increasing the specific air flow from 0.5 to 1.0 vvm in constant fed-batch (Cfb) resulted in a 33% yield increase, reaching 1706.40 mg PRP.L\u22121. However, the highest PRP concentration was achieved using exponential fed-batch with cell recycling (EfbCR), resulting in 1879.28 mg PRP.L\u22121. Although EfbCR offered high productivity, the Cfb strategy emerged to be the most technically feasible and robust solution and was successfully scaled up to an 80 L bioreactor, achieving 1885 mg PRP.L\u22121. These results advance understanding of PRP production by Hib and provides valuable insight into an efficient and simplified strategy for producing this key\/vital vaccine antigen. The findings support the potential for cost-effective local production in public health initiatives.<\/jats:p>","DOI":"10.3390\/bioengineering13020249","type":"journal-article","created":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T13:08:23Z","timestamp":1771592903000},"page":"249","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Simple Fed-Batch Strategy for Production of Capsular Polysaccharide by Haemophilus influenzae b at Pilot Scale"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8203-6960","authenticated-orcid":false,"given":"Mateus Ribeiro","family":"da Silva","sequence":"first","affiliation":[{"name":"Process Development Laboratory, Development and Innovation Center, Butantan Institute, S\u00e3o Paulo 05503-900, SP, Brazil"},{"name":"Bioprocess Laboratory, University of Campinas, UNICAMP, Campinas 13083-970, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia Maria Ferreira","family":"Albani","sequence":"additional","affiliation":[{"name":"Process Development Laboratory, Development and Innovation Center, Butantan Institute, S\u00e3o Paulo 05503-900, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joaquin","family":"Cabrera-Crespo","sequence":"additional","affiliation":[{"name":"Process Development Laboratory, Development and Innovation Center, Butantan Institute, S\u00e3o Paulo 05503-900, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2902-0983","authenticated-orcid":false,"given":"Jos\u00e9 Geraldo","family":"da Cruz Pradella","sequence":"additional","affiliation":[{"name":"Bioprocess Laboratory\u2014IP&D, University of the Paraiba Valley, UNIVAP, S\u00e3o Jos\u00e9 dos Campos 12000-000, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0978-4070","authenticated-orcid":false,"given":"Mickie","family":"Takagi","sequence":"additional","affiliation":[{"name":"Process Development Laboratory, Development and Innovation Center, Butantan Institute, S\u00e3o Paulo 05503-900, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1128\/CMR.13.2.302","article-title":"Worldwide Haemophilus influenzae type b disease at the beginning of the 21 st century: Global analysis of the disease burden 25 years after the use of the polysaccharide vaccine and a decade after the advent of conjugates","volume":"13","author":"Peltola","year":"2000","journal-title":"Clin. 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