Hepatitis B virus (HBV) is an infection with highest prevalences in Asia and sub-Saharan regions of the world where temperatures may vary widely, and where cold storage is not readily available. These are also regions where universal vaccination against HBV infection is essential to break the long-standing cycle of mother-to-infant transmission of this virus. HBV vaccine is a heat-labile product that must be stored between 2Β°C to 8Β°C in single-or multidose vials. Any potential deterioration in its potency during exposure to adverse conditions has been tested by prolonged exposure to high temperatures. The recombinant yeast-derived HBV vaccine, Engerix-B, was exposed to temperatures of 45Β°C for 1 week or to temperatures of 37Β°C for 1 month. One hundred thirty-eight volunteers were immunized with these exposed lots, and high rates of protective immunity achieved, without adverse reactions, 1 indicated that the immunogenicity of the vaccine would be preserved even in suboptimal environmental conditions.
Such reports of the stability of HBV vaccine in potentially adverse environments are misleading. They underestimate the ground realities of environmental hazards that are encountered in the field. Moreover, assessment of adequate immunogenicity may be inaccurate, because vaccine failures are often not apparent until many years after immunization. HBV infection in infants and preschool-aged children are typically subclinical without clinical manifestations of an episode of acute viral hepatitis. 2 Thus, vaccine failures would not be evident either at the time of initial vaccination or even at the completion of several vaccine doses. Many decades would need to elapse before inadvertent failure would become clinically apparent with symptoms of chronic hepatitis, cirrhosis, or primary hepatocellular carcinoma.
Quantification of the potency lots of HBV vaccine is a complex procedure. Unlike live measles or poliomyelitis vaccines that are quantified by inoculations of cell cultures in vitro, validation of HBV vaccine lots requires inoculation in human volunteers or experimental animals in vivo. The lack of an in vitro assay greatly limits our ability to measure the potency of a large number of HBV vaccine lots that have been exposed to ''field conditions.'' Frequent assessment of potency will not be practical until simple in vitro assays are routinely available.
To optimize immunogenicity, vaccine manufacturers should be aware of variations in temperature, humidity, air velocity,