Elena Govorkova, MD, PhD, Robert G. Webster, PhD, and coworkers at St. Jude Children's Research Hospital in Memphis, Tenn., used reverse genetics to develop an influenza virus with two key proteins on its surface derived from an H5N1 strain. They inactivated the virus and used it to vaccinate ferrets. The vaccine protected the ferrets from getting sick when exposed not only to the flu strain from which the vaccine was made, but also two other strains, including a deadly strain labeled A/Vietnam/1203/04.
Cross-strain protection is exactly what one would need, as it would protect against newly emerging variants until a strain-specific vaccine can be developed. The reverse genetics method used by the St. Jude investigators would allow rapid vaccine preparation, which is crucial in a potentially fast-moving pandemic. Other undertaken vaccine approaches have serious shortcomings. Wild-type H5N1 vaccines, for example, cannot be produced on a large scale because of their marked virulence, and vaccines based on less-virulent H5N1 strains have so far been relatively poor stimulators of immunity in human trials.
In the study, the ferrets were vaccinated intramuscularly with one or two doses of vaccine. Both schedules induced a protective antibody response, but the two-dose schedule induced higher levels of antibodies that were cross-reactive to various H5N1 viruses. Human clinical trials have seen similar results, suggesting that two doses of vaccine will be required to effectively protect against an H5N1 flu strain.
In an accompanying editorial, Alan W. Hampson, MSc, of the Australian Influenza Specialist Group, noted that the succe ssful use of a genetically modified whole-virus vaccine that produced protective antibodies against H5N1 virus in ferrets suggests that the ferret model has the potential to provide useful information in assessing vaccines when human data alone are inadequate.
"Possibly the greatest significance of the current study, he added, "is the demonstration of a significant cross-strain protective effect," a finding that "strengthens the argument for stockpiling vaccines prepared from currently available H5N1 vaccine strains."