Publication of PowderMed's Phase I Influenza DNA Vaccine Trial

This is an important paper.  "Epidermal DNA vaccine for influenza is immunogenic in humans," is "in press" at Vaccine (PubMed), accessible online even though it is undergoing final review.  The manuscript describes initial results from vaccination with a plasmid-based vaccine containing the HA domain of the H3 Panama strain.  I wrote briefly about this last year.

The details:

  • The vaccine appeared well tolerated, with some reaction to the physical effects of the vaccine that amounted to at most a slight rash.  Standard reactions to flu vaccination were observed, including fatigue, fever, headaches.  No antibodies to the double-stranded vaccine itself were detected.
  • The antibody titers are as reported previously, and this paper claims, "The present study is the first successful demonstration of immunogenicity of an influenza DNA vaccine in humans."
  • Increasing doses of the vaccine (up to 4 micrograms) induced increasing antibody titers, with only the largest dose meeting the 21 license requirement of the Committee for Proprietary Medical Products in the European Union.  I would observe that this is still a factor of 250 lower than any intramuscular DNA vaccine up to this point, and well within doses reasonable for widespread manufacturing and inoculation.  The specific antibody kinetics of vaccination with DNA are still unclear, and the authors note that, "The immune response to the DNA vaccine in humans may be qualitatively different than the response to protein vaccines."  Something that requires further study, to be sure.

In addition to the speed, manufacturing, and distribution advantages of DNA vaccines over egg- or cell culture-based approaches, it should be possible to achieve vaccination against multiple strains with one shot.  This could be accomplished either by including plasmids coding for multiple antigenic domains or by tailoring sequences to achieve cross-protection from the same antigen.  That is, it appears careful choice of the antigenic domain can result in the production of antibodies that neutralize more than one strain of a pathogen.

Given that 1) we very likely cannot know ahead of time the sequence of the virus that results in a pandemic, 2) flu viruses have been demonstrated to escape vaccines within 12 months, and 3) traditional vaccines aren't up to the job anyway, DNA vaccines may provide a way to inoculate people against more than one strain.  Because we are slowly developing the capability to monitor the virus in bird populations as well as humans (an endeavor that should have been given a much higher priority in the recent supplemental budget request),  it may soon be possible to include a distribution of antigenic sequences in any given round of inoculations.  This is speculative, to be sure, because there are currently no demonstrated ways of estimating which sequences are likely to be produced by mutation or recombination, but in principle we could produce vaccines effective against a whole range of pathogens, even those that have yet to appear in nature.

However, it is clear we have a lot to learn before this is possible.  A recent review paper in the Japanese Journal of Infectious Disease explores, "Mechanisms of Broad Cross-Protection Provided by Influenza Virus Infection and Their Application to Vaccines."

Hmmm...I was about to write a short summary of this paper, but I'm realizing it will take a bit me longer to digest the contents and do the subject justice.  So, I'll post again on cross-protection and the flu when I have a better grasp of it.