Preparedness against pandemic influenza: Production of an oil-in-water emulsion adjuvant in Brazil

PLoS One. 2020 Jun 3;15(6):e0233632. doi: 10.1371/journal.pone.0233632. eCollection 2020.

Abstract

Increasing pandemic influenza vaccine manufacturing capacity is considered strategic by WHO. Adjuvant use is key in this strategy in order to spare the vaccine doses and by increasing immune protection. We describe here the production and stability studies of a squalene based oil-in-water emulsion, adjuvant IB160, and the immune response of the H7N9 vaccine combined with IB160. To qualify the production of IB160 we produced 10 consistency lots of IB160 and the average results were: pH 6.4±0.05; squalene 48.8±.0.03 mg/ml; osmolality 47.6±6.9 mmol/kg; Z-average 157±2 nm, with polydispersity index (PDI) of 0.085±0.024 and endotoxin levels <0.5 EU/mL. The emulsion particle size was stable for at least six months at 25°C and 24 months at 4-8°C. Two doses of H7N9 vaccine formulated at 7.5 μg/dose or 15 μg/dose with adjuvant IB160 showed a significant increase of hemagglutination inhibition (HAI) titers in sera of immunized BALB/c mice when compared to control sera from animals immunized with the H7N9 antigens without adjuvant. Thus the antigen-sparing capacity of IB160 can potentially increase the production of the H7N9 pandemic vaccine and represents an important achievement for preparedness against pandemic influenza and a successful North (IDRI) to South (Butantan Institute) technology transfer for the production of the adjuvant emulsion IB160.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adjuvants, Pharmaceutic / chemical synthesis*
  • Adjuvants, Pharmaceutic / chemistry
  • Animals
  • Brazil / epidemiology
  • Drug Stability
  • Emulsions / chemical synthesis*
  • Emulsions / chemistry
  • Hemagglutination Inhibition Tests
  • Humans
  • Influenza A Virus, H7N9 Subtype / immunology*
  • Influenza Vaccines / immunology
  • Influenza, Human / epidemiology*
  • Influenza, Human / prevention & control*
  • Influenza, Human / virology
  • Mice
  • Mice, Inbred BALB C
  • Orthomyxoviridae Infections / prevention & control*
  • Orthomyxoviridae Infections / virology
  • Pandemics / prevention & control*
  • Polysorbates / chemistry
  • Squalene / chemistry
  • Technology Transfer
  • Vaccination / methods

Substances

  • Adjuvants, Pharmaceutic
  • Emulsions
  • Influenza Vaccines
  • Polysorbates
  • Squalene

Grants and funding

This project has been funded in whole or in part with Federal funds from the U.S. Department of Health and Human Services, Office of the Assistant Secretary for Preparedness and Response, Biomedical Advanced Research and Development Authority – BARDA (Grant n°. IDSEP140022 and IDSEP130015), received by CF; an Institutional Grant to Butantan Institute from World Health Organization – WHO (grant SPHQ13-LOA-316) and Brazilian agencies: Fundação de Amparo à Pesquisa do Estado de São Paulo - FAPESP (grant n°. 2015/25055-8) and Conselho Nacional de Desenvolvimento Científico e Tecnológico - CNPq (grant n°. 306992/2014-0) to PLH and Fundação Butantan for Laboratory maintenance. There was no additional external funding received for this study. The content is solely the responsibility of the authors and does not necessarily represent the official views of the U.S. Department of Health and Human Services; Office of the Assistant Secretary for Preparedness and Response; Biomedical Advanced Research and Development Authority. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.