Study Describes Advantages of Acambis' Clonal Smallpox Vaccine

CAMBRIDGE, England, and CAMBRIDGE, Mass. -- A new smallpox vaccine developed by Acambis is made in modern cell-culture system, is free from contaminating bacteria and viruses, and could be less neurovirulent than a first-generation vaccine while providing equivalent immunogenicity, according to pre-clinical data published in Nature Medicine.

Acambis' vaccine was developed in response to the U.S. 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.

Old, "first-generation" smallpox vaccines were grown in the skin of calves or other large animals. As such a production method 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.

Acambis derived its new vaccine from Dryvax, a first-generation vaccine registered in the US and used during the worldwide smallpox eradication program. In the initial phase of this work, Acambis discovered that the first-generation vaccine contained multiple subpopulations of virus, including variants that were highly virulent in pre-clinical models. As this observation fitted with previous research (see notes 1, 2), it was not considered acceptable to generate the new vaccine simply by inoculation of the first-generation product into cell culture. Consequently, Acambis 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. Through a series of pre-clinical tests, Acambis selected a preferred vaccine candidate that was consistently less virulent and provided equivalent protection.

A randomized, double-blind clinical study was carried out under an Investigational New Drug Application approved by the Food and Drug Administration (FDA) to evaluate the safety, tolerability and immunogenicity of Acambis' vaccine and Dryvax in 60 healthy adults aged 18 to 29 who had not previously been vaccinated against smallpox. The trial reinforced the findings of the pre-clinical tests, with the two vaccines having equivalent protection profiles and no serious adverse events being recorded.

Dr Thomas Monath, Acambis' chief scientific officer, commented, "The development of a clonal vaccine that can be manufactured using modern cell-culture methods indicates that Acambis' new smallpox vaccine represents an advance over the first-generation vaccine in terms of purity, quality, freedom from bacterial contamination allowed in the old vaccine and the absence of bovine adventitious agents. While we can not prove, without large- scale human experience, that our vaccine is safer for humans with respect to a lower incidence of postvaccinal encephalitis, this remains a possibility based on the pre-clinical data."

Notes:

1. Kutinova, L. et al. Search for optimal parent for recombinant vaccinia virus vaccines. Study of three vaccinia virus vaccinal strains and several virus lines derived from them. Vaccine 13, 487- 493 (1995).

2. Kutinova, L. et al. Influence of the parental virus strain on the virulence and immunogenicity of recombinant vaccinia viruses expressing HBV pre-S2-S protein or VZV glycoprotein l. Vaccine 14, 1045-1052 (1996).

Source: Acambis