THERMOSTABILIZATION OF LIVE VIRUS-VACCINES BY HEAVY-WATER (D2O)

Eradication of poliomyelitis is based on the mass administration of or al poliovirus vaccine (OPV). Delivery of effective vaccines in the dev eloping world especially in tropical areas, is compromised when refrig eration 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 con centration (potency) of each of the three component serotypes, measure d in tissue culture infective closes, should not decrease by more than 0.5 log(10) before vaccine delivery. High concentration (1 M) of MgCl 2 is currently used as stabilizer for OPV. The stabilizing effect of D 2O was tested here on OPV strains. By diluting the viral suspension wi th D2O-based salt and buffer solutions, in a manner similar to that in volved in OPV production, an 87% concentration of D2O in the final vir al preparation was achieved. In severe conditions of testing (incubati on for 3 days at 45 degrees C), the Sabin 3 virus lost an average of 2 .7 log(10) potency in the presence of 87% D2O as compared to 3.0 log(1 0) in H2O-based IM MgCl2, and to 5.7 log(10) 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 log(10) potency after 3 days cat 45 de grees C. Similar thermostabilizing tlffects 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 infecti vity of the three D2O MgCl2-treated OPV strains remained in the limit of requirements (less than or equal to 0.5 log(10)). The stabilizing e ffect of D2O was also demonstrated on yellowfever 170 vaccine virus st rain. D2O alone or in combination with other stabilizers such as MgCl2 , could thus be considered as a candidate for the improvement of live virus vaccine thermostability.