DNA PROVIDES BETTER FLU VACCINE
By Sean Henahan, Access Excellence
An experimental DNA plasmid vaccine appears to
overcome some of the limitations of current vaccines by offering
protection against a wide variety of strains, report researchers.
The influenza virus provides a moving target to current
vaccine products, as it constantly
changes and evolves to avoid the human antibody and cell-based
defensive systems. Since current killed-virus vaccines are
typically made from the three most common strains of flu from the
previous year's victims, public health authorities are always
playing a game of catch-up.
In a series of animal experiments, immunization with a DNA
vaccine designed to induce antibodies against influenza antigens
provided both homologous and cross-strain protection against
various strains of human influenza, reported Dr. Margaret A.
Liu, Departments of Virus and Cell Biology, Merck Research
Laboratories, West Point, Pennsylvania.
DNA-based vaccines incorporate DNA coding for virus
proteins, in a plasmid (small autonomous DNA sequences that are
easily manipulated in the laboratory). The plasmid vaccine is
introduced into the host where it produces the viral proteins (in
the absence of intact virus) to which the host immune system
raises an antibody and cell-based defense, thus priming the host
for a subsequent attack. The experimental DNA influenza virus
vaccine is based on sequences that do not readily mutate each
The researchers used the ferret influenza challenge model,
since the antibody responses of ferrets to influenza infection
parallel those of humans in their ability to distinguish between
antigenic variants, noted Dr. Liu.
The DNA vaccine provided significantly better protection
against several strains of influenza compared with current
killed-virus vaccines. As expected, immunization with
hemaglutination DNA alone was most effective when the immunogen
exactly matched the challenge strain. A combination of HA DNA and
internal protein DNA from various flu strains provided
significant cross protection.
DNA vaccines offer a number of potential advantages over
immunization with vaccines made from whole inactivated virus,
subunit vaccines, or recombinant products. For example, the DNA
vaccines have the potential to protect against different
antigenic variants. Also, since DNA vaccines are derived directly
from human specimens, problems with divergent mutants can be
minimized. The DNA vaccines should also be easier to manufacture.
Another potential advantage of the DNA vaccine is that it
may induce presentation of epitopes that more closely resemble
those found in native flu virus compared with viral proteins
produces in E.Coli, yeast or insect cells. DNA vaccines also do
not require the use of formalin (used to inactivate whole virus)
which may help preserve amino acid side chains in key epitopes.
"Thus far, DNA vaccines have induced robust primary and
secondary immune responses in a variety of animal systems. The
experience with live DNA virus vaccines including small pox,
adenovirus and varicella, points towards the anticipated safety
of DNA vaccines," noted Dr. Liu.
Researchers have yet ot prove the safety and efficacy of DNA
vaccines in humans. Several issues remain to be addressed. These
include: concerns over the potential for induction of tolerance;
and clinically significant immune responses against the injected
DNA. Another concern is that the injected DNA may randomly
integrate into the genome.
"The efficacy of DNA immunization has also been demonstrated
for a variety of viral, bacterial, parasitic and cancer models.
These studies together indicate the potential of this technology
for the development of both animal and human vaccines. DNA
immunization holds substantial promise as an outstanding
contribution of biotechnology to modern medicine," noted Pierre
Meulien, Department of Research, Pasteur-Merieux, France.
For more information on DNA flu vaccines see: Nature
Medicine, 6/96, v.1, no.6, Liu et al and comments by Meulein et