Safer smallpox vaccine from Acambis

A novel smallpox vaccine developed by the UK's Acambis may be less neurovirulent than Wyeth's first-generation vaccine Dryvax, which is registered in the USA, while still providing equivalent immunogenicity.

Acambis' vaccine was developed in response to the US Government's requirement for a stockpile of smallpox vaccine for use in the event of an outbreak, including the potential of smallpox being used as a bioterrorist weapon.

Older first-generation smallpox vaccines were grown in the skin of calves or other large animals, a method that is considered unacceptable today. Acambis aimed to develop a vaccine that was suitable for modern manufacture in cell culture and that matched or exceeded first-generation in immunogenicity but did not exceed it in virulence markers that might indicate reactogenicity in humans.

The report, in Nature Medicine​, explains that Acambis modelled its vaccine on Dryvax but found that it contained multiple subpopulations of virus, including variants that were highly virulent in pre-clinical models. "It was not considered acceptable to generate the new vaccine simply by inoculation of the first-generation product into cell culture,"​ according to Acambis.

The company prepared a number of viral clones from which one could be chosen that closely resembled the first-generation vaccine's profile but had an acceptable or improved safety profile. Use of a clone also removed possible adventitious viral contaminants and ensured consistency of manufacture.

These preclinical results have been reinforced by a randomised, double-blind trial evaluating the safety, tolerability and immunogenicity of Acambis' vaccine and Dryvax in 60 healthy volunteers aged 18 to 29, who had not previously been vaccinated against smallpox. The findings of the study confirmed that the two vaccines had similar protection and safety profiles.