Technology transfer of oil-in-water emulsion adjuvant manufacturing for pandemic influenza vaccine production in Romania

Infectious Disease Research Institute, 1124 Columbia St., Ste 400, Seattle, WA 98104, United States. Electronic address: .
Vaccine (Impact Factor: 3.62). 10/2012; 31(12). DOI: 10.1016/j.vaccine.2012.10.048
Source: PubMed


Many developing countries lack or have inadequate pandemic influenza vaccine manufacturing capacity. In the 2009 H1N1 pandemic, this led to delayed and inadequate vaccine coverage in the developing world. Thus, bolstering developing country influenza vaccine manufacturing capacity is urgently needed. The Cantacuzino Institute in Bucharest, Romania has been producing seasonal influenza vaccine since the 1970s, and has the capacity to produce ∼5 million doses of monovalent vaccine in the event of an influenza pandemic. Inclusion of an adjuvant in the vaccine could enable antigen dose sparing, expanding vaccine coverage and potentially allowing universal vaccination of the Romanian population and possibly neighboring countries. However, adjuvant formulation and manufacturing know-how are difficult to access. This manuscript describes the successful transfer of oil-in-water emulsion adjuvant manufacturing and quality control technologies from the Infectious Disease Research Institute in Seattle, USA to the Cantacuzino Institute. By describing the challenges and accomplishments of the project, it is hoped that the knowledge and experience gained will benefit other institutes involved in similar technology transfer projects designed to facilitate increased vaccine manufacturing capacity in developing countries'.

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Available from: Adrian Onu, Jun 10, 2015
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    • "Oil-in-water emulsions are very effective adjuvants for pandemic influenza vaccines and stimulate approvable HI titers in adults, young children and infants at substantially reduced doses of antigen [6]–[11]. These adjuvants are prepared by mixing shark-derived squalene and egg phosphatidylcholine oils with an aqueous buffered solution containing glycerol and the surfactant poloxamer 188, followed by high pressure homogenization and filtering [19]. Mechanistically, emulsions induce a chemokine-driven gradient at the site of injection that recruits leukocyte infiltration and antigen transport to local lymph nodes, and their induction of broadly reactive CD4 T cells predict the rise of neutralizing antibody titers after booster immunizations [20], [21]. "
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    ABSTRACT: The ongoing threat from Influenza necessitates the development of new vaccine and adjuvant technologies that can maximize vaccine immunogenicity, shorten production cycles, and increase global vaccine supply. Currently, the most successful adjuvants for Influenza vaccines are squalene-based oil-in-water emulsions. These adjuvants enhance seroprotective antibody titers to homologous and heterologous strains of virus, and augment a significant dose sparing activity that could improve vaccine manufacturing capacity. As an alternative to an emulsion, we tested a simple lipid-based aqueous formulation containing a synthetic TLR4 ligand (GLA-AF) for its ability to enhance protection against H5N1 infection. GLA-AF was very effective in adjuvanting recombinant H5 hemagglutinin antigen (rH5) in mice and was as potent as the stable emulsion, SE. Both adjuvants induced similar antibody titers using a sub-microgram dose of rH5, and both conferred complete protection against a highly pathogenic H5N1 challenge. However, GLA-AF was the superior adjuvant in ferrets. GLA-AF stimulated a broader antibody response than SE after both the prime and boost immunization with rH5, and ferrets were better protected against homologous and heterologous strains of H5N1 virus. Thus, GLA-AF is a potent emulsion-free adjuvant that warrants consideration for pandemic influenza vaccine development.
    PLoS ONE 02/2014; 9(2):e88979. DOI:10.1371/journal.pone.0088979 · 3.23 Impact Factor
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