Codon pair bias and viral vaccine design

Live attenuated vaccines (LAVs) have prevented morbidity and mortality against a number of important viral diseases (such as smallpox and polio) via long-lived humoral and cell-mediated immunity. Unlike inactivated, subunit or recombinant protein vaccines which require multiple inoculations this cost-effective approach requires only one or two doses to generate a robust immune response. Furthermore, live vaccines are able to elicit both mucosal and systemic protective responses. Unfortunately, conventional LAVs have two major drawbacks. Firstly, attenuation of the pathogenic phenotype by either random gene mutation or by passage in unnatural conditions depends on chance and cannot be universally applied to a variety of virus types. Secondly, since viruses are generally attenuated on the basis of only a few mutations the risk of reversion to virulence remains a key aspect of developing attenuated virus vaccines.