Inovio Pharmaceuticals (AMEX:INO) said Wednesday that its SynCon avian flu vaccine generated protective antibody responses against six different H5N1 virus strains in a phase I trial, a key step in the company's path to develop universal flu vaccines.
The company said that with the robust antibody and T cell responses generated, it has achieved proof of principle.
By design, Inovio's SynCon flu vaccine is not matched to any single virus.
The company's SynCon technology allows it to design synthetic
vaccines with the potential to protect against unmatched sub-types and
strains of pathogens, including newly emergent, unknown strains of a
virus that will periodically emerge through mutation, as in the case of
Importantly, the company said the avian flu vaccine generated a
hemagglutination inhibition (HAI) titer of 1:40 or higher against at
least one of the six tested H5N1 strains in 8 of 17, or 47 per cent, of
HAI measurements from the blood are used to assess the generation of
protective HA antibody responses generated by a vaccine. Generating an
HAI titer of 1:20 is generally regarded as a positive response to the
vaccine, while a titer of 1:40 or higher in the blood of vaccinated
subjects is generally associated with protection against seasonal flu
viruses and has been observed in multiple subtypes, Inovio said.
Twelve of 17, or 71 per cent of vaccines generated an HAI titer of
1:20 or higher, indicating a positive vaccine response, against at least
one H5N1 strain.
In an unprecedented result, two vaccinated subjects demonstrated an HAI titer of 1:20 or higher against all six strains tested.
"Our goal has been to develop a truly universal influenza vaccine
capable of providing years of protection across subtypes and strains,"
said president and CEO, Dr. J. Joseph Kim.
"The protective levels of antibody responses generated by our
universal H5N1 vaccine against diverse unmatched strains of this
dangerous subtype provides proof of principle for our SynCon universal
flu program and our other antibody-based vaccine products.
"We are planning further development initiatives for this program and
look forward to forthcoming data from INO-3510, our universal vaccine
for the influenza H5N1 and H1N1."
The major challenge to developing broadly effective vaccines against
the flu is that within subtypes, there are hundreds of strains that can
vary slightly and that can frequently mutate to create new strains, the
Today's vaccines provide protection by matching targeted virus
strains, which are those predicted to an issue in the next flu season -
but they often fail to be protective because the predicted strains often
change as the next flu season emerges.
Subtypes can also reassort, Inovio said, meaning strains from
different subtypes combine with one another, which is usually the cause
of pandemic flu outbreaks.
For example, a strain of the deadly influenza subtype H5N1, which has
killed about 60 per cent of everyone infected by the virus but does not
currently pass easily from person to person, may combine with a strain
of H1N1 or other subtype that has a high infection rate - creating a
more virulent new strain.
Inovio also said that several recent published studies have shown
that current H5N1 viruses can be manipulated to become more infectious.
There is therefore a clear need for universal flu vaccines capable of protecting against multiple, changing strains of the flu.
In the phase I study reported on Wednesday, a total of 17 patients
completed a full H5N1 immunization regimen, consisting of two
intramuscular vaccinations with a synthetic DNA vaccine encoding three
flu antigens. This was followed by two intradermal vaccinations of only
the HA antigen, using Inovio's skin electroporation device.
The vaccine was found to be well tolerated at each immunization.
Reported adverse events and injection site reactions were mild to
moderate and required no treatment, the company said.
Previously, Inovio reported that two intramuscular immunizations
alone generated strong T cell immune responses against 72 per cent of
the vaccinated subjects. The T cell responses from this study "mirrored
the best-in-class T cell responses" generated from Inovio's other Phase I
SynCon vaccine trials for HIV and cervical cancer/dysplasia, the
Inovio is advancing its universal flu vaccine strategy with a second
phase I influenza vaccine study, which will test the INO-3510
multi-subtype SynCon vaccine consisting of the H5N1 and H1N1 subtypes,
delivered only through intradermal electroporation.
The aim is to provide cross-strain protection against H1N1 and H5N1 viruses.
The company is also advancing its H3N2 and Type B SynCon vaccines
through preclinical development. Its plan is to combine these components
into a single universal flu vaccine, which could protect against
multiple divergent strains of seasonal and pandemic flu viruses.
Inovio's clinical programs include phase II studies for cervical
dysplasia, leukemia and hepatitis C virus and phase I studies for
influenza and HIV.