H1N1/FLU

The H1N1 swine flu virus was
discovered in Mexico in March 2010.  
In Hong Kong, 282 people developed
severe complications from the virus,
and 80 of them died. More than 18,200
people died worldwide, according to
the World Health Organization.


FDA APPROVES  FIRST  
MICROINJECTION FLU VACCINE
The FDA has approved the first
influenza vaccine administered through
a novel intradermal microinjection.
The Fluzone Intradermal vaccine is
injected through an ultra-fine, 0.6 inch
needle that is 90% shorter than most
intramuscular flu vaccine needles,
according to a statement from
manufacturer Sanofi Pasteur.

The vaccine works by generating an
immune response from dendritic cells
in the skin, according to the statement.

The Fluzone Intradermal vaccine is
indicated for adult patients (age 18 to
64) for the subtype A and type B
influenza virus, and consists of a 0.5
mL or 0.1 mL, prefilled dosage with 15
mcg and 9 mcg of hemagglutinin,
respectively, per strain of influenza.

Approval was based on phase III
clinical trial data of 4,276 adults
randomized to receive Fluzone via
intradermal or intramuscular routes.
Those in the intradermal group had a
similar immunologic response to those
in the intramuscular group.

Adverse reactions to the vaccine
included visible injection-site events
such as redness, swelling, induration,
pain, and itching.

The vaccine is inserted at the very top
layer of the skin as it is a key
component of the immune system
which contains a large number of
immune cells, called dendritic cells that
capture and process the antigen and
effectively stimulate an immune
response.

The dermis and epidermis of the
human skin are rich in antigen-
presenting cells. It has been proposed
that delivery of vaccine antigens to
these tissues (i.e., intradermal
delivery) rather  than to muscle or
subcutaneous tissue could therefore
induce superior protective immune
responses and that smaller quantities
of vaccine antigen could be delivered
via the intradermal (ID) route, thus
making it dose-sparing.

These attributes might be particularly
meaningful to immunization programs
in low- and middle-income countries by
potentially  reducing the cost of
vaccines, increasing vaccine
availability where manufacturing
capacity is  limited, and providing more
effective vaccination.

Several novel devices for IDD
(intradermal delivery) of vaccines are
being developed; each offering a
different set  of benefits:

• Devices that use liquid formulations
and are not prefilled (disposable-
syringe jet  injectors, hollow
microneedles mounted on syringes,
and ID needles) probably offer
the fastest and lowest risk route to
evaluating IDD in the clinic.

• Prefilled syringes with a single ID
needle are commercially available, but
their  development and production
requires the involvement of the
vaccine producer.

• Solid microneedles coated with
vaccine or composed of vaccine, offer
additional  advantages, but are further
behind in development and are a
higher commercial and regulatory risk
due to the need to formulate the
vaccine specifically for this
presentation and because novel
production methods are used.




PROMISING NEW DRUGS FOR
UPCOMING  H1N1 SEASONS
Current treatment options for
pandemic H1N1 flu are quite limited, so
new drugs are badly needed.
One of those drugs is favipiravir,  
made by Toyama Chemical Co., Ltd.
Favipiravir is an oral RNA polymerase
inhibitor effective against both
influenza A and B as well as other RNA
viruses. It is in Phase III testing in
Japan. Importantly, it has no cross-
resistance with the neuraminidase
inhibitors or amantadines.

The other is laninamivir made by Biota
Scientific Management Pty Ltd.
Laninamivir is a neuraminidase
inhibitor administered only by
inhalation. However, the drug has an
extremely long half-life such that a
single inhalation constitutes an entire
course of treatment. Laninamivir is
effective against tamiflu-resistant
isolates. It is in Phase III trials in
Australia, where it is establishing a
very favorable safety profile, according
to Dr. Weinberg, professor of
medicine, pediatrics, and pathology of
the University of Colorado, Denver.

During the 2009 pandemic doctors
basically had only tamiflu and relenza
to fight with.
These were supplemented during the
pandemic by intravenous peramivir, a
drug that was in Phase III trials but was
decreed available for use in critically ill
patients as a result of an Emergency
Use Authorization. The Emergency Use
Authorization was terminated in June
2010.
Peramivir is a potent, intravenously
administered anti-viral agent that
rapidly delivers high plasma
concentrations to the sites of infection.
Made by BioCryst, peramivir inhibits
the interactions of influenza
neuraminidase, an enzyme that is
critical to the spread of influenza within
the host.
Intravenous relenza became available
on a compassionate use basis during
the pandemic. Unlike peramivir, it is
effective against tamiflu-resistant
isolates.
Ribavirin is commercially available for
indications other than influenza.
However, it does have in vitro activity
against influenza, and although it's not
a very good anti-influenza drug by
itself, it may have a future in
combination therapy for severe
pandemic H1N1 disease.

Tamiflu  performed well in the 2009
season against pandemic H1N1. When
started within 2 days following
symptom onset, it reduced mortality by
50%. It also reduced the duration of
symptoms.  Tamiflu did a good job of
limiting disease transmission during
outbreaks in nursing homes and other
closed communities.

Under an Emergency Use
Authorization issued during the 2009
pandemic, tamiflu became available for
the treatment of patients of all ages
with H1N1 flu, from newborns up to old
age.  A trial suggest the best dose in
infants is 3 mg/kg/dose twice daily.

There was concern that tamiflu
resistance would spread widely
through communities, but that didn't
prove to be the case.



PLANT BASED H1N1 VACCINE
PRODUCTION
The Defense Advanced Research
Projects Agency (DARPA) has
awarded Medicago a $21 million
research grant to improve the process
of large-quantity H1N1 vaccine
production using plant-based
technology.
Medicago, Inc., is a publicly traded
company based in Quebec, Canada.

The company is currently using
tobacco leaves to produce pandemic
and seasonal influenza vaccines.
Medicago’s project with DARPA will
lead to a total investment of more than
$32 million in North Carolina, US.
Medicago USA is developing vaccines
for humans based on two proprietary
technologies; plant-based
manufacturing technology and its virus-
like-particles (VLPs). VLPs can be
rapidly and efficiently produced and
isolated from plant leaves and closely
resemble a virus, allowing them to be
recognized readily by the immune
system, yet they are completely non-
infectious and unable to replicate,
making for a very safe vaccine.

Virus-Like Particles (VLPs) represent
one of the most exciting emerging
vaccine technologies for generating
effective and long-lasting protection.
VLPs consist of  protein shells studded
with short strands of the proteins
specific to whatever disease the
vaccine is intended to control. VLPs
are made to look like a virus, allowing
them to be recognized readily by the
body's immune system, however, they
lack the core genetic material, making
them non-infectious and unable to
replicate. Unlike current influenza
vaccines that are manufactured with
an inactivated virus, VLP-based
vaccines do no require an actual
sample of the virus, they simply require
the genetic sequence of the virus or
bacteria.

To effectively respond to emerging
diseases, the ability to rapidly produce
vaccines or therapeutic antibodies in
the face of an outbreak such as
pandemic influenza is critical.
Medicago has developed the Proficia
technology, a proprietary alternative to
current egg-based and cell production
systems. Using whole living plants as
hosts, our Proficia technology is a
rapid, flexible, high yielding and robust
vaccine and antibody production
system. A major advantage of this
system based on transient protein
expression in plant leaves is
unmatched speed. Vaccine production
can be initiated within less than three
weeks from the identification of the
genetic sequence from a pandemic or
seasonal influenza strain.


OVERVIEW
Flu  Season

Four drugs are on the market for
treating flu but the two older ones,
amantadine and rimantadine, are
not used because most flu strains
resist their effects.
Roche AG and Gilead Sciences
Inc's pill  tamiflu, is the favored drug
but must be taken quickly to be
useful. Flu viruses develop
resistance to it quickly.
GlaxoSmithKline's and Biota Inc's
Relenza also works against the
known circulating flu strains but
must be inhaled.

Since current treatment options for
pandemic H1N1 flu are quite
limited, so new drugs are badly
needed.

One of those new drugs is
favipiravir, made by Toyama
Chemical Co., Ltd.
Favipiravir is an oral RNA
polymerase inhibitor effective
against both influenza A and B as
well as other RNA viruses. It is in
Phase III testing in Japan.
Importantly, it has no cross-
resistance with the neuraminidase
inhibitors or amantadines.

Laninamivir is a long-acting
neuraminadase inhibitor. It is in the
same class of drugs as Relenza
and Tamiflu but persists longer in
the body.
Laninamivir is co-owned  by Biota
Scientific Management Pty Ltd. and
Daiichi Sankyo. The drug has an
extremely long half-life such that a
single inhalation constitutes an
entire course of treatment.
Laninamivir is effective against
tamiflu-resistant isolates. It is in
Phase III trials in Australia, where it
is establishing a very favorable
safety profile.

Peramivir is being developed by
Shionogi in Japan.  During the
pandemic in 2009  the intravenous
peramivir, a drug that was in Phase
III trials at the time,  was decreed
available for use in critically ill
patients by the  Emergency Use
Authorization. This authorization
was terminated in June 2010.
Peramivir is a potent, intravenously
administered anti-viral agent that
rapidly delivers high plasma
concentrations to the sites of
infection. Peramivir inhibits the
interactions of influenza
neuraminidase, an enzyme that is
critical to the spread of influenza
within the host.
Permavir is a good drug for
severely ill flu patients as there is
demand for intravenously
administered drugs for such
patients.

Hong Kong researchers have
developed a treatment for people
infected by swine flu using the
antibodies from blood plasma from
patients who recovered from the
disease.  30 critically ill patients in
Hong Kong were given the
treatment after they failed to
respond to antiviral drugs Tamilflu
and Relenza and most recovered.

Antibodies in the plasma can kill
the H1N1 virus in severely ill
patients.
Dr. Ivan Hung, assistant professor
of medicine at the University of
Hong Kong, who led the study, said:
"Some of them died subsequently,
but we have enough evidence to
conclude that the antibodies are an
effective cure, as most patients
have since recovered." Dr. Hung
thought the treatment could also be
effective against other viruses.

Influenza viruses are particularly
difficult to combat because they
mutate rapidly. Thus, to fight the
seasonal flu,  vaccine
manufacturers must try to predict
which strains will dominate the next
season before they can begin to
develop formulations to confer
immunity. Anyone who wants
protection must get an annual shot.


This brings into sharper focus the
need for a real solution to the
problem which is the need for
developing a  universal flu vaccine.

Why is it that two shots of measles
vaccine given during childhood
protect a person for life and four
shots of polio vaccine do the same,
but flu shots must be received every
year? And why do flu vaccines still
provide less-than-complete
protection?

The answer lies not just in the very
structure of the flu virus, but in
particular that area we have been
targeting since vaccination against
flu first became possible in the
1940s, when the US military
developed the first approved
inactivated vaccines for influenza,
which were used in the Second
World War. (The first seasonal
influenza vaccine in the United
States became available in 1945.)

"When you are vaccinated or mount
an immune response naturally,"
explains researcher Wayne M
Marasco, the antibodies you
produce target a "lollipop-shaped
protein called hemagglutinin, which
has a big, globular head on a
narrow stalk. That globular head is
like a decoy," he says. "It changes
every season." But the stalk does
not.

Scientists may have found the
Achilles heel of flu viruses.
Researchers including Wayne A.
Marasco, an associate professor of
medicine at Harvard Medical
School, and colleagues from the
Centers for Disease Control and
Prevention and the Burnham
Institute for Medical Research, have
discovered an antibody that is
active against many different
strains of influenza, including the
1918 Spanish flu, the H5N1 bird flu,
and the largest group of seasonal
flus.

The  discovery by Marasco and his
collaborators raises the possibility
of a universal flu vaccine that he
says would confer "durable
immunity, much like a tetanus shot,"
against a range of influenza strains.
The antibody targets a stable part
of the viral entry mechanism that
doesn't change from year to year
and is nearly identical across
genetically different families of flu.

In influenza infection, the
hemagglutinin proteins extending
from the virus attach to cell surfaces
in the respiratory tract, then unfold
to expose a harpoon-like fusion
protein that spears the target cell
membrane. The protein then twists
into a hairpin formation that pulls
the viral membrane and the cell
membrane into tight contact.
Because the two membranes are
both formed of lipids, they start to
mix, and eventually a pore forms
between them, as can happen
between two soap bubbles. The
pore then elongates to become a
stable neck, allowing the viral RNA
to enter the targeted cell. The virus
then takes over the nucleus,
hijacking the cell's reproductive
machinery to make copies of itself.

Marasco and colleagues "found an
evolutionarily stable region in the
base of the 'stalk' where all the
fusion machinery that the virus uses
to enter the cell is located." The
naturally occurring, but rare,
antibody they discovered binds to a
pocket in the stalk, where its
stranglehold prevents the virus from
unfolding and injecting its genetic
payload into another cell.
A vaccine able to prompt the
human immune system to produce
antibodies that would bind to this
pocket would confer immunity to a
broad range of flu viruses.

The researchers are now focused
on finding antibodies that will target
the two other major classes of
human influenza.

Earlier in 2010  Dana-Farber and
the Sanford-Burnham Medical
Research Institute had signed a
license agreement   with
Genentech/ Roche, giving the
company exclusive rights to
manufacture, develop and market
human monoclonal antibodies to
treat and protect against group 1
influenza viruses using the new
experimental technology.

Other developments:

The United States has contracted
with five companies to make
influenza immunizations for the U.S.
market -- Novartis, Sanofi, CSL,
AstraZeneca unit MedImmune and
GlaxoSmithKline. MedImmune's
vaccine is needle-free and
delivered by sprayer.

Vaccine maker Sanofi Aventis
asked U.S. regulators  to approve a
new flu vaccine, Fluzone
Intradermal Vaccine  that uses a
short, thin needle.

Sanofi says the new vaccine,
developed with syringe maker
Becton Dickinson, may hurt less
than standard vaccines, does a
better job of stimulating protection
against influenza, and requires less
of the active ingredient.

The company said the U.S. Food
and Drug Administration had
accepted the application and it
hoped the agency would decide
whether to approve it by early next
year. The vaccine is approved for
use in Europe.

Most adult flu vaccines are given
using a needle 1 inch to 1.5 inches
(25 mm to 40 mm) long that goes
into muscle tissue.

Sanofi's new needle is one-tenth
that long, just 1.5 mm, and the
vaccine uses one-fifth the usual
amount of the active ingredient,
called antigen.

Sanofi's short needle approach is
called an intradermal vaccine. Many
studies have shown that delivering
flu vaccine into the skin activates
specialized immune system cells
called dendritic cells that help
protect against infectious disease.
Zicam Cold Remedy Zavors helps to
reduce the severity of cold symptoms
such as sore throat, stuffy nose,
sneezing, coughing and congestion
when taken at the first sign of a cold.












Vicks Pure Warm Mist Humidifier for
Relief of Cold & Flu Symptoms. This
humidifier boils water to a pure steam
vapor up to 96% bacteria free. This
mixes with dry air in the cooling
chamber to release warm, moist air
into the room.