Vaccines:  


PLANT BASED FLU  VACCINE
PRODUCTION
In July 2011 Canada's Medicago says
the company's Phase II trial of its
vaccine for avian flu elicited a solid
immune response and was found to be
safe and well tolerated. Notably, the
vaccine was equally effective in older
and younger subjects, which  could be
a key selling point for the shot.

Medicago's H5N1 vaccine candidate
was formulated to protect against the
Indonesian influenza virus. It is
manufactured in Nicotiana
benthamiana, a relative of the tobacco
plant, using the Company's proprietary
VLP technology.

VLPs may have several advantages
over traditional flu vaccines. They 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.
Medicago's technology only requires
the genetic sequence of a viral strain
and not the live influenza virus. This
key difference allows vaccines to be
manufactured within four weeks of
obtaining the genetic sequence of a
pandemic strain. This is in contrast
with current manufacturing
technologies which rely on strain
adaptation and can only deliver a
vaccine six to nine months after a
pandemic is declared.

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.

Medicago is on the verge of opening a
90,000-square-foot facility in Research
Triangle Park, NC to help manufacture
VLP plant-based vaccine technology.
The developer expects to have
commercial capacity by tha fall of 2011.




DARPA'S PLANT BASED RAPID
VACCINE PROGRAM
Project GreenVax, which utilizes
tobacco plants rather than the current
egg-based vaccine technology, holds
the promise of shortening vaccine
production to a fraction of the current
time, allowing rapid response to newly
emerging viruses not possible with
current technology.

Project GreenVax was designed for a
projected final scale capacity of 100
million doses per month. The flexibility
of the plant-based system, combined
with its low cost and ability to massively
scale, may provide vaccine protection
not only to citizens of the United
States, but to many parts of the world
that cannot currently afford vaccines.

Xcellerex, Inc. announced  that Project
GreenVax has agreed to acquire XDR
GMP single-use production bioreactors
from Xcellerex. The systems will be
deployed in a new facility currently
under construction in Bryan, Texas.
Project GreenVax is spearheaded by
Texas Plant-Expressed Vaccine
Consortium, which consists of G-Con,
LLC and The Texas A&M University
System and financed largely by
DARPA, the Pentagon's research outfit.

The GreenVax Project will be
headquartered on a secure, 21-acre
site on the campus of the Texas A&M
Health Science Center in Bryan,
Texas. The custom-designed 145,000
square foot biotherapeutic production
facility will be constructed and
managed by G-Con.

Xcellerex is revolutionizing the way
biomolecules are developed,
manufactured and commercialized.
The company’s unique single-use
component technology platform
transforms biomanufacturing
economics, enabling the development
of biotherapeutics and vaccines, and
dramatically improving the ability of
Xcellerex and its partners to deploy
manufacturing capacity.

Xcellerex leverages its technology and
services platform by: 1)
commercializing its FlexFactories®
(complete, turnkey, modular
production facilities) and enabling
single-use unit operations (unique,
integrated XDR bioreactors, XDM
mixing systems and related single-use
assemblies)and 2) enabling its
partners to accelerate time-to-GMP
manufacturing and the clinic by
leveraging it FlexFactory
manufacturing know-how, services
capacity, and TransPlant capability
and 3) creatively structuring
transactions around FlexFactories,
XDRs and its FlexFactory
manufacturing services.

Based in Marlborough, Massachusetts,
Xcellerex is backed by an experienced
management team and top-tier venture
investors including Kleiner Perkins
Caufield & Byers, VantagePoint
Venture Partners and SCG Capital.


VACCINE FOR SHINGLES TESTED IN
PHASE 3
GlaxoSmithKline commenced the
Phase III trials for the vaccine, which
has been designed to test its safety,
efficacy and immunogenicity in more
than 30,000 around the globe.
Shingles (herpes zoster) is a painful,
blistering skin rash due to the varicella-
zoster virus, the virus that causes
chickenpox.  The disease can occur at
all ages (though incidence increases
with age), and there are an estimated
one million cases per year in the US
alone.
Should the vaccine  make it to market
it will compete with Merck’s offering
Zostavax, a live, attenuated vaccine
launched across the Atlantic for adults
aged 60 and over and in Europe for
those aged 50 and above back in May
2006.


DENGUE VACCINE TESTED
After more than a decade of
development, the National Institute of
Allergy and Infectious Diseases (NIAID)
has started clinical trials to test a
vaccine to protect against the dengue
virus, a product researchers hope may
one day help prevent a disease to
which 2.5 billion people are exposed.

Dengue is "caused by any of four
related viruses –  DENV-1, DENV-2,
DENV-3 and DENV-4," which are
transmitted to humans by Aedes
mosquitoes.  The disease is prevalent
in the tropical and subtropical regions
of the world. Of the estimated 50
million to 100 million people infected
annually, it kills about 25,000, mostly
children. The new vaccine is
tetravalent, meaning that it is designed
to protect against all four dengue
viruses.





NEW CHEAPER  MENINGITIS VACCINE
A cheap new vaccine against
Meningitis A recently approved by the
World Health Organization (WHO) is
being described as a "game changer"
that will bring hope to the 430 million
people at risk of the disease in the so-
called Meningitis Belt, in Sub-Saharan
Africa.

The new vaccine is the result of a
collaboration between the Meningitis
Vaccine Project (MVP, a partnership
between the WHO and the non-profit
organization PATH which is funded by
the Bill & Melinda Gates Foundation),
and an Indian manufacturer, the
Serum Institute of India who will make
the vaccine at an agreed starting price
of 0.40 US dollars (30 UK pence) per
dose.

The disease is most prevalent in the
Meningitis Belt that stretches from
Senegal and the Gambia in the West
to Ethiopia in the East, with epidemics
occuring during the dry season from
December to June. An epidemic wave
can last up to three years, dying out
during the rainy season.

The size of the epidemics in Africa is
staggering: in the 1990s when there
was a Meningitis C outbreak in the UK
it killed 1,000 people, meanwhile at the
same time, a Meningitis A outbreak
killed more than 100,000 people in
Africa.
Mass roll out of the new Meningitis A
vaccine will start this autumn in Mali,
Burkina Faso and Niger with backing
from Global Alliance for Vaccines and
Immunization (GAVI) and WHO.



VACCINE NEXVAX2  TO DESENSITIZE
PEOPLE WITH CELIAC DISEASE     
Melbourne biotech company Nexpep
has created a vaccine to desensitise
people with celiac disease to gluten.

The intolerance to gluten, the main
protein in wheat, rye and barley,
causes the immune system to attack
the gut.

Now British and Australian scientists
have pinpointed why the protein can
be so toxic.

They gave 200 patients bread, rye
muffins or boiled barley to eat and,
tested their blood six days later to see
how their immune systems responded.
This showed that 90 of the 2,700
protein fragments that make up gluten
had been treated as toxic by their
bodies.
But three were particularly bad, the
journal Science Translational Medicine
reported.
Melbourne-based researcher Dr Bob
Anderson said: 'These three
components account for the majority of
the immune response to gluten.'

Nexpep has  recently completed a
clinical trial testing the vaccine. Trial
no: NCT00879749.



STIMUVAX VACCINE FOR BREAST
TUMOR PATIENTS
Stimuvax cancer vaccine for breast
tumor patients by Merck KGaA;
Stimuvax is an innovative cancer
vaccine designed to induce an immune
response to cancer cells that express
MUC1, a protein antigen widely
expressed on common cancers. MUC1
is over expressed on many cancers
such as lung cancer, breast cancer,
prostate cancer and colorectal cancer.
Stimuvax is being developed by Merck
KGaA of Darmstadt, Germany  under a
license agreement with Oncothyreon.
Merck is currently conducting three
Phase 3 trials of Stimuvax.


CANCER VACCINE TG4010  FOR
NON-SMALL-CELL LUNG CANCER
Transgene SA, of Paris  is developing
cancer vaccine TG4010, which is set
to start Phase IIb/III testing in non-small-
cell lung cancer patients by the end of
2010.

VACCINE PROVENGE FOR
PROSTATE CANCER
The Food and Drug Administration  
approved the first vaccine to treat
prostate cancer.
The $93,000 a year  vaccine,
Provenge, made by Dendreon,  
doesn't prevent cancer, unlike the
polio shot or recently approved
vaccines that block infection with
viruses that cause most cervical
tumors.
Provenge also doesn't cure cancer.
But studies show that the vaccine does
help men with advanced prostate
cancer live four months longer than
men given placebo shots.
Provenge works in a unique way. The
series of three shots are custom-
made, using a patient's own cells, and
are designed to train the immune
system to recognize and kill malignant
cells. Although the immune system
naturally destroys many abnormal cells
and foreign invaders, such as viruses,
cancers appear to have an unusual
ability to evade detection.


VACCINE CVAC TO TREAT OVARIAN
CANCER
There is a quiet  bit of research into
developing a vaccine, not to prevent,
but to treat ovarian cancer. The idea
behind these vaccines is to stimulate
the body's own immune system to
target and destroy tumor cells.
An Australian company, Prima Biomed,
has performed a number of clinical
trials with its vaccine CVac. Using a
novel technology, CVac's
immunotherapy works by teaching the
immune system to recognise the tumor
cells as foreign. Dendritic cells are
removed from the patient and
stimulated with mannan fusion protein
(MFP), consisting of the antigenic
portion of the tumor antigen mucin-1
(MUC-1) fused to the immune-
enhancing sugar mannan. The cells
are then reinfused back into the
patient to generate primarily a T-cell-
based immune response against the
MUC-1-expressing tumor.




OTHER DEVELOPMENTS
Prevnar 13 vaccine by Pfizer for
children's pneumonia

Merck's new rotavirus vaccine
TotaTeq;

Antigenics kidney cancer vaccine
Oncophage;

Celldex Therapeutics Inc. and partner
Pfizer Inc.has cancer vaccine CDX-110
for newly diagnosed  glioblastoma
multiforme;


GARDASIL NOT APPROVED FOR
OLDER WOMEN
The FDA has rejected Merck's  
request to market its HPV vaccine
Gardasil to women between the ages
of 27 and 45. The company had hoped
the expanded use could boost
slumping sales, which dropped 12
percent to $988 million in 2010,
despite the 2009 addition of men and
boys ages 9 to 26 to the potential
patient list. Recently, the shot was also
approved for anal cancer prevention.

According to Merck's release, the
vaccine failed to provide adequate
results for trial patients and also didn't
prevent cervical dysplasia or other
HPV-related diseases in the 27 to 45
age range.





OVERVIEW

Accelerated
Vaccine
Production
The U.S. government has been
pushing for the development of an
antidote to the swine flu in the wake
of last year's H1N1 pandemic. The
outbreak turned out to be milder
than feared, but the flu scare
demonstrated that existing methods
of vaccine production were too slow
to respond in time to avert a major
public health crisis.

Recent problems with egg-based
vaccine manufacture—such as
unexpected contamination,
unprecedented shortages of
special pathogen-free eggs, and
inability to grow certain dangerous
viruses in eggs—have
demonstrated vulnerabilities in
current manufacturing methods.
In addition,  the identity of many
new biological threat agents are
unlikely to be known in advance and
therefore  stockpiling of
countermeasures cannot be
performed.

Darpa's (Defense Advanced
Research Projects Agency of the
US military)  Accelerated
Manufacture of Pharmaceuticals
(AMP) Program seeks to produce
therapeutics or vaccines "on
demand," in large quantity, at low
cost, to interdict both established
and new biological threats. The
goal of the program is to create an
extremely rapid, flexible, and cost-
effective manufacturing system
capable of producing 3 million
doses of GMP (Good
Manufacturing Practices) quality
vaccines or monoclonal antibodies
(mAB) within 12 weeks.
To achieve this goal, the AMP
Program is divided into three
phases of escalating capability.
Each phase has milestones that
require logarithmic improvements
(10X between each phase) in
efficiency, production speed, and
cost effectiveness.
DARPA will specify the protein or
monoclonal antibody to be
expressed. To demonstrate the
AMP platform scalability,in true
military fashion,  there will be a
"Live Fire Test" to produce 1,000
bulk doses at lab-scale against an
unknown agent in 12 weeks.

In May of 2010 Xcellerex, Inc. and
Pfenex Inc. along with deltaDOT
Ltd. and BioPharm Services have
successfully demonstrated the
production of purified swine flu H1
hemagglutinin (California strain) in
42 days starting from the amino
acid sequence of the protein.
During that period, the gene was
cloned and expressed,
fermentation and purification
processes developed, and the
quality product shown to be fully
within the specifications. The test
results exceeded the goal for rate
of production by at least 10 fold.

Project GreenVax, which utilizes
tobacco plants rather than the
current egg-based vaccine
technology, holds the promise of
shortening vaccine production to a
fraction of the current time, allowing
rapid response to newly emerging
viruses not possible with current
technology.

Project GreenVax was designed for
a projected final scale capacity of
100 million doses per month. The
flexibility of the plant-based system,
combined with its low cost and
ability to massively scale, may
provide vaccine protection not only
to citizens of the United States, but
to many parts of the world that
cannot currently afford vaccines.

Xcellerex, Inc. announced  that
Project GreenVax has agreed to
acquire XDR GMP single-use
production bioreactors from
Xcellerex. The systems will be
deployed in a new facility currently
under construction in Bryan, Texas.
Project GreenVax is spearheaded
by Texas Plant-Expressed Vaccine
Consortium, which consists of G-
Con, LLC and The Texas A&M
University System and financed
largely by DARPA, the Pentagon's
research outfit.

The GreenVax Project will be
headquartered on a secure, 21-
acre site on the campus of the
Texas A&M Health Science Center
in Bryan, Texas. The custom-
designed 145,000 square foot
biotherapeutic production facility
will be constructed and managed
by G-Con.

Xcellerex is revolutionizing the way
biomolecules are developed,
manufactured and commercialized.
The company’s unique single-use
component technology platform
transforms biomanufacturing
economics.

Xcellerex leverages its technology
and services platform by: 1)
commercializing its FlexFactories
(complete, turnkey, modular
production facilities) and enabling
single-use unit operations (unique,
integrated XDR bioreactors, XDM
mixing systems and related single-
use assemblies)and 2) enabling its
partners to accelerate time-to-GMP
manufacturing and the clinic by
leveraging its FlexFactory
manufacturing know-how, services
capacity, and TransPlant capability
and 3) creatively structuring
transactions around FlexFactories,
XDRs and its FlexFactory
manufacturing services.

Based in Marlborough,
Massachusetts, Xcellerex is
backed by an experienced
management team and top-tier
venture investors including Kleiner
Perkins Caufield & Byers,
VantagePoint Venture Partners and
SCG Capital.


Medicago, a Canadian firm
specializes in producing vaccines
by growing viruslike cultures on
tobacco leaves, a process that
reduces the time needed to create
vaccines from six months to several
weeks.
Plant-based vaccine production
offers cost advantages.
Building greenhouses is more cost
effective than the sterilized
facilities, expensive manufacturing
technology and stainless steel
tanks required for the insect or
mammalian cell cultures.
The other cost advantages relate to
vaccine purification and
formulation. Purification from plant
extracts is simpler because there
are  no viruses in plants which can
infect humans, so you don't have to
worry about viral removal.

In the tobacco plants specially
designed "virus-like" nanoparticles
are produced. At about 25
nanometers in diameter, the
particles are about the same size
as the norovirus, but they consist
only of the outer surface protein -
the portion of the virus recognized
by the human immune system. The
particles contain none of the
infectious material of the original
virus, but they stimulate a robust
immune response from the human
body to fight off an actual infection.

Virus-like particles look just like a
live virus, but they are hollow shells
without a genome inside and they
cannot reproduce. Because they
look like the virus, they evoke a
more robust immune response
against the real thing.

To produce VLS vaccines all you
need is the sequence online, you
don't even need  physical  samples
of the virus in hand.

One VLP-based vaccine already is
on the market, namely the human
papilloma virus (HPV) vaccine.

Medicago will build a 90,000-
square-foot facility in Research
Triangle Park in North Carolina.
When the new facility is completed
in 14 months, it will have the
capacity to create 10 million doses
of vaccine per month. The facility
will include a greenhouse to
cultivate 14,000 tobacco plants,
labs to extract vaccines from the
plants and administrative offices.

Medicago will grow tobacco plants
from seed and submerge 5-week-
old plants in a chemical bath
containing proteins that will be used
to make vaccines. The proteins will
grow on the tobacco leaves and will
be extracted after five days. After
the proteins are removed, the
plants will be destroyed.
The plant used in vaccine
production is not the same species
of tobacco used to make cigarettes.
Other companies have worked with
this technology but either ran out of
cash or ran out of time before they
could commercialize their product.

Medicago's lead vaccine
candidate, H5N1, has successfully
completed a Phase I clinical trial
and will be entering Phase II in
2010.
Its technology has the potential to
deliver a vaccine for testing in
about a month after the
identification and reception of
genetic sequences from a
pandemic strain.

IBio Inc, another biotech firm that's
working on plant-based vaccines,
plan to conduct human trials of an
H5N1 vaccine during 2010.