A January post on one of my favourite science blogs raised an interesting question about vaccination as selective pressure. As part of her highly recommended “Viruses are Cool” series, Mad Hatter discussed a potential universal flu vaccine that should be effective against multiple strains of the virus, removing the need for annual shots against the strain that is most likely to cause problems in a given year.

The downside is that immunising everyone with the universal strain might put pressure on the targeted viral protein to evolve into a form that can evade the host’s vaccine-stimulated antibodies.

I left a comment on the post saying the following:

“I don’t know much about immunisation – would pre-existing immunity against the virus be as strong a selective pressure as, say, an antibiotic would be against bacteria? I’m thinking that if the infection can’t even get started then there might not be enough rounds of viral replication for new mutations to appear very often, whereas antibiotics are usually introduced once the infection is already established and replication is in full swing.”

Mad Hatter replied:

“I’m no expert on immunization either, but viruses might be able to replicate for a few cycles in some immunized individuals. It’s entirely possible people who have had the flu shot still get infected at a cellular level, but the infection is subclinical or asymptomatic. And for the small RNA viruses, one round of replication may be enough to produce a huge viral mutant repertoire.”

(Sorry for the bulk copy and pasting, it’s all relevant, honest!).

Well, a paper just came out in Virology Journal, entitled Avian influenza: genetic evolution under vaccination pressure. As you might expect from the title, the paper demonstrates that the avian flu virus does indeed evolve in vaccinated populations, and will provide a basis for the kind of studies that might answer the questions that Mad Hatter and I discussed.

Magdalena Escorcia and colleagues from around Mexico and the US isolated flu virus from chickens that had been vaccinated under the the Mexican government’s 14-year old avian influenza vaccination programme, but that were nonetheless displaying some signs of infection. The vaccine strain was derived from the most common variant infecting chickens in 1994, and the same viral strain has been used to vaccinate birds ever since.

The authors found considerable variation in the sequences of the isolated virus – namely between 0.4 and 13.2% nucleotide difference from the vaccine strain. Strains isolated in the same year tended to cluster together, as expected if the virus constantly evolves.

So I guess Mad Hatter was right – viruses must be able to replicate, and therefore accumulate mutations, to some limited extent in immunised individuals. This has important consequences for vaccination programmes and probably explains the apparent increase in flu symptoms observed in the Mexican poultry industry. Perhaps a new vaccine will be required soon.

I hope the people who are coordinating our protection against avian flu are paying attention…