Thermostabilization of live virus vaccines by heavy water (D2O).
Eradication of poliomyelitis is based on the mass administration of oral poliovirus vaccine (OPV). Delivery of effective vaccines in the developing world, especially in tropical areas, is compromised when refrigeration cannot be assured. The OPV, prepared with three live attenuated polioviruses (Sabin strains, serotypes 1, 2 and 3), is considered to be the most thermolabile of vaccines in the World Health Organization's Expanded programme on Immunization. To be effective, the initial concentration (potency of each of the three component serotypes, measured in tissue culture infective doses, should not decrease by more than 0.5 log10 before vaccine delivery. High concentration (1 M) of MgCl2 is currently used as stabilizer for OPV. The stabilizing effect of D2O was tested here on OPV strains. By diluting the viral suspension with D2O-based salt and buffer solutions, in a manner similar to that involved in OPV production an 87% concentration of D2O in the final viral preparation was achieved. In severe conditions of testing (incubation for 3 days at 45 degrees C), the Sabin 3 virus lost an average of 2.7 log10 potency in the presence of 87% D2 as compared to 3.0 log10 in H2O-based 1 M MgCl2, and to 5.7 log10 in the H2O-based control solutions. When tested in a combined 87% D2O and 1 M MgCl2 treatment, the Sabin 3 virus lost only 1.3 log10 potency after 3 days at 45 degrees C. Similar thermostabilizing effects were obtained for Sabin 1 and Sabin 2 strains, but the level of stabilization was slightly lower. Tested in standard conditions at 37 degrees C for 7 days, the infectivity of the three D2O MgCl2-treated OPV strains remained in the limit of requirements ( < or = 0.5 log10). The stabilizing effect of D2O was also demonstrated on yellow fever 17D vaccine virus strain.
D002460:Cell Line; D017666:Deuterium Oxide / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006358:Hot Temperature; D006801:Humans; D015636:Magnesium Chloride / Q000494:pharmacology; D017955:Poliovirus / Q000187:drug effects*; D011055:Poliovirus Vaccine, Oral
D011055:Poliovirus Vaccine, Oral; D015636:Magnesium Chloride; D017666:Deuterium Oxide