The thermal stability of yellow fever vaccines

Abstract

The assessment of yellow fever vaccine thermostability both in lyophilized form and after reconstitution were analyzed. Two commercial yellow fever vaccines were assayed for their thermal stability. Vaccines were exposed to test temperatures in the range of 8 degrees C to 45 degrees C. Residual infectivity was measured by a plaque assay using Vero cells. The titre values were used in an accelerated degradation test that follows the Arrhenius equation and the minimum immunizing dose was assumed to be 10(3) particles forming unit (pfu)/dose. Some of the most relevant results include that (i) regular culture medium show the same degradation pattern of a reconstituted 17D-204 vaccine; (ii) reconstituted YF-17D-204 showed a predictable half life of more than six days if kept at 0 degrees C; (iii) there are differences in thermostability between different products that are probably due to both presence of stabilizers in the preparation and the modernization in the vaccine production; (iv) it is important to establish a proper correlation between the mouse infectivity test and the plaque assay since the last appears to be more simple, economical, and practical for small laboratories to assess the potency of the vaccine, and (v) the accelerated degradation test appears to be the best procedure to quantify the thermostability of biological products.

Yellow fever virus: historical and current issues regarding recent epidemics and vaccination in Brazil

“…The previous rationale for vaccine disposal was the loss of infective potential to immunize, but experiments showed that the vaccine virus was still viable for at least twice the recommended time after opening the vial. 14 In 1943, there was an initial publication indicating YFV persistence in experimentally infected nonhuman primate hosts. 15 Two decades later, the persistence of YFV neutralizing antibodies was demonstrated in the sera of persons who had received a single dose of 17DD vaccine 17 years prior.…”

Effect of Freezing on Oxytocin Ampules

“…The estimated half life of the vaccine infectivity is 3 to 10 months at room temperature, from 10 to 20 days at 37°C, and about two days at 46°C (21,46). The time required to reduce the initial titer of the vaccine to 1000 infective units is between 2.6 to 6.1 days at 46°C, 5.7 to 15.7 days at 37°C and 12.4 to 26 days at 31°C (67). In 1987, a study of 11 YF vaccines was sent to WHO by manufacturers.…”

“…However, when the reconstituted vaccine is exposed to elevated temperatures, it quickly deteriorates. At 37°C, 31°C and 27°C, the reconstituted vaccine lost 50% of its infectivity following 1.5, 3.1 and 4.9 hour exposures (21,67). An exposure of reconstituted vaccine for one hour to 46°C resulted in a 0.5 log 10 loss, and after a two-hour exposure, the loss of infectivity exceeded 1 log 10 (21).…”

Estudios de estabilidad térmica sobre el ingrediente farmacéutico activo de la vacuna gavac®

“…La estabilidad térmica de vacunas ha sido evaluada por diferentes autores. Por ejemplo, se evaluó la termoestabilidad de la vacuna contra la fiebre amarilla, tanto en su forma liofilizada como después de la reconstitución, exponiéndolas a temperaturas en el rango de 8 a 45°C[6]. Por otro lado, emplearon el ensayo de hemoaglutinación para determinar la estabilidad térmica a 36ºC de las cepas Hitchner-B1 (B1), LaSota (L) y Komarov (K) de la vacuna contra la enfermedad de Newcastle[7].…”