Development and technology transfer of Haemophilus influenzae type b conjugate vaccines for developing countries. Vaccine

Unit Vaccinology, Centre for Infectious Disease Control (CIb), National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720 BA Bilthoven, The Netherlands.
Vaccine (Impact Factor: 3.62). 06/2012; 30(33):4897-906. DOI: 10.1016/j.vaccine.2012.05.058
Source: PubMed


This paper describes the development of a Haemophilus influenzae type b (Hib) conjugate vaccine at the National Institute for Public Health and the Environment/Netherlands Vaccine Institute (RIVM/NVI, Bilthoven, The Netherlands), and the subsequent transfer of its production process to manufacturers in developing countries. In 1998, at the outset of the project, the majority of the world's children were not immunized against Hib because of the high price and limited supply of the conjugate vaccines, due partly to the fact that local manufacturers in developing countries did not master the Hib conjugate production technology. To address this problem, the RIVM/NVI has developed a robust Hib conjugate vaccine production process based on a proven model, and transferred this technology to several partners in India, Indonesia, Korea and China. As a result, emerging manufacturers in developing countries acquired modern technologies previously unavailable to them. This has in turn facilitated their approach to producing other conjugate vaccines. As an additional spin-off from the project, a World Health Organization (WHO) Hib quality control (QC) course was designed and conducted at the RIVM/NVI, resulting in an increased regulatory capacity for conjugate vaccines in developing countries at the National Regulatory Authority (NRA) level. For the local populations, this has translated into an increased and sustainable supply of affordable Hib conjugate-containing combination vaccines. During the course of this project, developing countries have demonstrated their ability to produce large quantities of high-quality modern vaccines after a successful transfer of the technology.

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    • "Although appropriate, these CGPC methods are very time-consuming and require careful handling and large amounts of product, in contrast to high-performance size exclusion chromatography (HPSEC) methods that allow for quicker analyses and the use of small amounts of product and a large choice of detectors. HPSEC has already been used to determine molecular size of bacterial polysaccharides [8,13–15] and conjugate vaccines [16] [17] [18] [19]. "
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    ABSTRACT: Current vaccines against Haemophilus influenzae type b (Hib) consist of the polyribosyl ribitol phosphate (PRP) capsular polysaccharide, chemically conjugated to a carrier protein. Among the various biological and physical analyses to be performed on these vaccines, the determination of the molecular size of the polysaccharide preparations throughout the conjugation process is particularly relevant. Comparison of results from high performance size exclusion chromatography (HPSEC) with those routinely obtained using conventional gel permeation chromatography (CGPC) methods highlights the correlation between the two methods for determining the values of the chromatographic distribution coefficient (KD) of native and activated polysaccharides. The resulting date showed that KD value is sufficient to characterize these polysaccharides using an HPSEC method. However additional molecular size parameters, i.e. molar mass and hydrodynamic radius, are necessary for a reliable characterization of the tetanus conjugate (PRP-T), certainly due to the lattice-like structure of the conjugate. In practice, an absolute detection system in HPSEC was used that was composed of a low-angle light scattering detector, a viscometer and RI detectors. As demonstrated, these HPSEC methods are rapid, accurate and reproducible for the polysaccharides and their glycoconjugates and provide a relevant and more informative alternative to the current CGPC methods.
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