The US Centers for Disease Control and Prevention’s (CDC) announcement that vials of smallpox “appearing to date from the 50s” had been found at a disused US Food and Drug Administration (FDA) lab in Bethesda, Maryland last night provoked responses ranging from panicky to waggish.
The UK’s Daily Mail said the discovery of the ”FORGOTTEN” virus was disturbing, while journalist Alexander Gaffney from the Regulatory Affairs Professionals Society (RAPS) jokily tweeted that the “FDA needs to send FDA a Form FDA-483, and probably a Warning letter.”
At the time of writing the CDC did not know if the six vials found at the laboratory contained live, potentially infectious virus but it is a possibility according to virus expert Professor Ian Jones from the University of Reading in the UK.
Jones told BioPharma-Reporter.com “Smallpox is at the bigger and stronger end of the viral spectrum” adding that “although the viability of the viruses would have fallen year-on-year, if the titre [the concentration of virus] had been high enough to begin with there could still be live virus, assuming the conditions in the FDA lab were appropriate.”
The point about appropriate conditions was echoed by Professor Polly Roy from the Department of Infectious & Tropical Diseases, London School of Hygiene & Tropical Medicine, who told us the “virus will survive if it is frozen properly, it will also be true for vaccine strains.”
To survive for long periods viruses - be they long forgotten stocks of smallpox in Government labs or attenuated components of an anti-infective – need to be kept in cool, dry conditions, which is a significant challenge for live attenuated vaccine (LAV) producers.
LAVs are vaccines that contain a hobbled version of an infective agent that is less virulent, but still capable of eliciting an immune response sufficient to protect a person if they come into contact with the wild-type virus.
Karl Melber, director of program management at vaccine technology firm Curevac, told us that: “In the past several smallpox vaccines based on live-attenuated vaccinia virus were manufactured. The virus preparation was supplemented with stabilizing agents and freeze-dried.”
“When properly stored at -20 °C the freeze-dried vaccine was supposed to be stable for long term, if not indefinitely. So a shelf-life of 60+ years may be theoretically possible, but will be difficult to prove for obvious reasons.”
Melber added that: “Freeze-drying is employed for other attenuated live-virus vaccines as well. However, the stability and viability of the resulting live-virus vaccines depends on the individual virus type and cannot be extrapolated from the example of poxviruses.”
Viability is key
Making sure that live vaccines are viable when they are administered is vitally important according to Prof Jones, who pointed to techniques like costly and time consuming techniques lyophilisation and use of compounds like trehalulose as evidence of the lengths manufacturers go to try and ensure that their products work.
“LAVs need to be stored at around 4 degrees Celsius, which is the real challenge of cold chain shipment” said Jones, adding that “if vaccine potency falls, then immune responses they elicit and protection they afford people also drops.”
“In such circumstances people may decide that vaccination does not work and stop seeking such protection, which could have serious consequences for disease prevention and control efforts.”