Inactivated poliovirus vaccine and test development at Connaught Laboratories Ltd.

Trivalent inactivated poliovirus vaccine (IPV) (MK) was made, purified, and inactivated according to the amended Rijks Instituut (The Netherlands) protocol from primary monkey kidney tissue grown on microcarrier cultures. Losses of the type 2 component due to adsorption to the glass ampule occurred with the purified vaccine preparation. This problem was solved by changing the diluent, and the vaccine was submitted for evaluation in clinical trials at Johns Hopkins (Baltimore, Md.). Phase 2 of the development was to standardize production of IPV from MRC-5 (human diploid) cells on microcarriers and otherwise follow the Rijks Instituut 's method. Results of experimental trivalent vaccine production and testing showed that the number of effective doses harvested from MRC-5 cell cultures compared favorably with vaccine derived from monkey kidney. The yields could be further increased with stearyl tyrosine as adjuvant. Large-scale production using 200-liter fermenters is in progress. Poliovirus particles of various densities in cesium chloride can be found in any IPV preparation and give rise to different immunogenic responses. As shown in this paper, some of these virus fractions produce a low primary humoral antibody response but appear to be important for memory induction.