Bulletin of the World Health Organization

Hepatitis B virus vaccine: during freezing or high temperature exposures

Article: Nelson et al. 2004;82:99-105

Investigations relating to inadvertent freezing of hepatitis B virus vaccine in Indonesia have been intriguing. Certainly, better strategies and systems for vaccine distribution would be designed to address local conditions and cold chain conditions [1]. Nevertheless, it would be essential to address basics of hepatitis B virus disease profile and the 2003 power failures in the Americas and Europe.

Assessment of immunogenicity of hepatitis B virus vaccine by conventional in vivo or any in vitro techniques might not be accurate and precise. Any vaccine failures with hepatitis B virus vaccine are often not apparent until many years after immunization. Hepatitis B virus infections in infants and pre-school children are typically sub clinical without a clinical manifestation of acute viral hepatitis [2]. Vaccine failures would not be apparent either at the time of vaccination or even after completion of several vaccine doses. Many decades would lapse before inadvertent failures would manifest clinically with chronic hepatitis, cirrhosis or primary hepatocellular carcinoma.

Recently, industrialized countries, known for their extremely reliable electricity supplies for decades, were in for an unexpected catastrophe. During the second weekend in August 2003, vast areas in Canada and eastern parts of the United States of America had massive power failures lasting several days. During August 2003 itself, there was a power failure during the last weekend in London. Furthermore, whole of Italy was plunged in darkness during the last September 2003 weekend. These power failures would have had a tremendous effect on the performance of cold chain appliances with the manufacturers. Moreover, several warehouses with large stockpiles of hepatitis B virus vaccines would have also not been spared.

With no prejudice to prospective modeling of flexible cold chain scenario and international policy discussion [1], researchers should be stimulated to offer ‘freeze-proof’ and still higher ambient temperature resistant vaccines. Experimental lots of the least stabilized common childhood vaccine, live poliovirus vaccine, have been stabilized by pre-addition of pirodavir and deuterium oxide. The stabilized lots resisted an exposure to 42oC for 10 hours [3]. Surely prospective lots of freeze-proof and higher ambient temperature resistant vaccines, along with regular international policy reviews [1], would be an asset to achieve the ultimate: a global eradication of hepatitis B virus.

Subhash C Arya, & Nirmala Agarwal, Sant Parmanand Hospital, 18 Alipore Road, Delhi-110054, India. Email: subhashji@hotmail.com


  • Nelson CM, Wibisono H, Purwanto H, et al. Hepatitis B vaccine freezing in the Indonesian cold chain: evidence and solutions. Bulletin of the World Health Organization. 2004;82:99-105
  • McMahon BJ, Alward WIM, Hall DB, et al. Acute hepatitis B virus infection: clinical expression of disease and subsequent development of carrier state. Journal of Infectious Diseases. 1985;151:599-603
  • Verheyden B, Andrus K, Rombart B. Capsid and RNA stabilization of oral poliovaccine. Vaccine 2001;19:1899-905