panflu Stats

H5N1 vaccine shows good immune response in adults

Mixin — Mon Nov 08, 2010 8:56 am

Author: Mixin

Posted: Mon Nov 08, 2010 8:56 am

A phase 3 trial of 550 adults found that an H5N1 influenza (avian flu) vaccine produced a strong immune response in adults, including those older than 60. The vaccine also produced a cross-reactive response to seasonal H1N1 strains but not seasonal A/H3N2 or B strains. Researchers gave the adults two doses 21 days apart of a Vero cell whole-virus vaccine without adjuvant. The researchers report, "The vaccine significantly increased the number of H5N1 specific and H5 haemagglutinin specific memory B cells, 6 months after the primary immunization." The immune response was not statistically different among those younger than 60, compared with the older cohort. The authors state that the vaccine "is capable of producing a good cross-clade cellular immune response," adding that "This is especially important since the clade from which a pandemic H5N1 strain will emerge in the future, if it does occur, will be difficult to predict."
http://www.cidrap.umn.edu/cidrap/content/influenza/avianflu/news/nov0510newsscan.html

study: Evaluation of the cellular immune responses induced by a non-adjuvanted inactivated whole virus A/H5N1/VN/1203 pandemic influenza vaccine in humans
Science Direct: http://tinyurl.com/255qjee

CAP Cells Suitable For Commercial Vaccine Production?

Mixin — Sat Nov 06, 2010 11:21 am

Author: Mixin

Posted: Sat Nov 06, 2010 11:21 am

this is a press release but the concept is worth consideration

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[snips]
Cologne, Germany, September 28, 2010 / b3c newswire / CEVEC Pharmaceuticals, the developer of an extremely potent protein expression system based on human CAP cells, announced today that CAP cells produce high virus titers upon infection with influenza strains. The virus titers are as good as or even higher than with MDCK and Vero cells, host cells currently used for influenza vaccine production.

"The infected CAP cells grow rapidly in serum-free and commercially available media. With an optimized medium even higher virus titers can be expected,'' added Wolfgang Kintzel, CEVEC's Chief Commercial Officer and Managing Director.
http://www.cevec-pharmaceuticals.com/news

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From a blog post

The CAP cell line is a stable, immortal cell line derived from human amniocytes. An amniocyte is a fetal cell suspended in the amniotic fluid, the same cells used for prenatal diagnosis of genetic disorders like Down's Syndrome, Zellweger Syndrome or Duchenne's Muscular Dystrophy.

A huge advantage to using CAP cells in genetic engineering is that protein products are glycosylated following human patterns of post-translational modification.

http://biotech.about.com/b/2010/11/02/amniocytes-the-future-of-vaccines.htm

3 Reports: Influenza virus characterisation, WHO Vax Choice

Mixin — Sun Oct 24, 2010 8:59 pm

Author: Mixin

Posted: Sun Oct 24, 2010 8:59 pm

Long .pdf's; second one gives a list of low reactors to at least one ferret antisera. Charts, graphs showing antigenic sites. Seasonal H1N1, pandemic H1N1, H3N2

Link to our post at FluTrackers
http://www.flutrackers.com/forum/showthread.php?t=154282

http://www.ecdc.europa.eu/en/publications/Publications/1001_Influenza_virus_characterisation_2010_JAN.pdf

http://www.nimr.mrc.ac.uk/documents/about/interim_report_feb_2010.pdf

http://influenza.rki.de/Saisonberichte/2009.pdf

Ampligen� and QS-21 Stimulon Adjuvant

Mixin — Tue Jul 13, 2010 7:09 pm

Author: Mixin

Posted: Tue Jul 13, 2010 7:09 pm

This is from a PR release:
...that summarizes the results of a three (3) year Japanese government funded program to develop and test a nasally delivered H5N1 (Avian Flu) vaccine which, when coupled with Ampligen�, an experimental therapeutic, provided a robust and long lasting immune response to the vaccine. The report, entitled "Research on Clinical Applications of Influenza Vaccines Formulated for Nasal Mucosal Delivery" was filed with Japan's Ministry of Health, Labor and Welfare (MHLW), which fully funded this work in non-human primates.

...in the group for which Ampligen twenty-fold was used, which showed the highest IgG antibody titer after half a year had passed, the value was maintained at at least 10 � 26 times, and that value was maintained even when a year had passed since vaccine inoculation. Moreover, the serum IgA antibody titer was at at least 10 � 23 times when half a year had passed, and that value was also maintained after one year had passed.
http://www.globenewswire.com//newsroom/news.html?ref=rss&d=196099

Here is the link to Japan's National Diet Library, where the report will be available for public viewing http://www.ndl.go.jp/en/index.html

DAS181 (Fludase) Anti-Influenza Drug Inhibits Parainfluenza

Mixin — Tue Jun 22, 2010 8:13 pm

Author: Mixin

Posted: Tue Jun 22, 2010 8:13 pm

Tests in mice showed Fludase, made by privately held NexBio, could stop parainfluenza viruses from replicating, the researchers reported in the Journal of Infectious Diseases.

Parainfluenza viruses are not closely related to flu but belong to another family of viruses called paramyxoviruses. They cause most cases of croup and can cause pneumonia and bronchiolitis - an inflammation of the small air passages in the lungs.

Parainfluenza uses the same receptors - molecular doorways - to infect cells as flu does. Fludase inactivates these receptors.

Development of Flu Vaccines Based on EB66 (Duck Cells)

Mixin — Fri Apr 09, 2010 8:07 am

Author: Mixin

Posted: Fri Apr 09, 2010 8:07 am

From a press release about Glaxo and VIVALIS collaborating to develop new influenza vaccines based on VIVALIS' innovative EB66(R) cell line technology.

The EB66(R) cells replicate a wide range of human and animal viruses and are currently used or being evaluated for the production of viral vaccines.

The EB66(R) stem cell line technology derived from duck embryonic stem cells and are easily genetically engineered to efficiently express recombinant proteins of interest ( > 1 g/l). Monoclonal antibodies produced in EB66(R) cells have human-like glycosylation profile, with the remarkable additional feature of having reduced fucose content. This latter characteristic provides a better cytotoxic activity to antibodies, particularly useful in the treatment of cancer cells.

DNA vaccine

gs — Sun Apr 04, 2010 1:23 pm

Author: gs

Posted: Sun Apr 04, 2010 1:23 pm

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2746192/?tool=pubmed

http://en.wikipedia.org/wiki/DNA_vaccination

http://www.ncbi.nlm.nih.gov/pubmed/20117262

http://dnavaccine.com/news.php

eggs: 20 weeks
DNA: 13 weeks

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2843722/?tool=pubmed
Therefore, while gene-based vaccination with NP and M2 may provide moderate levels of protection against low challenge doses, it is insufficient to confer protective immunity against high challenge doses of H5N1 in ferrets. These immunogens may require combinatorial vaccination with HA, which confers protection even against very high doses of lethal viral challenge

link to Inovio press statement

�If we achieve similar results in human studies, this universal vaccine concept has the potential to shift the current reactive paradigm of influenza vaccine design, manufacturing, and delivery. Such a shift would provide tremendous health and economic benefits worldwide�

chart of Inovio,Vical

LJ001: Broad Spectrum Antiviral

Mixin — Tue Feb 02, 2010 12:07 pm

Author: Mixin

Posted: Tue Feb 02, 2010 12:07 pm

the abstract is also posted in our summary forum
----------------------------------------------------

We provide evidence that the small molecule- a rhodanine derivative that the researchers have dubbed LJ001- binds to both cellular and viral membranes, but its preferential ability to inactivate viral membranes comes from its ability to exploit the biogenic reparative ability of metabolically active cells versus static viral membranes, he (Dr. Lee) said. That is, at antiviral concentrations, any damage it does to the cell's membrane can be repaired, while damage done to static viral membranes, which have no inherent regenerative capacity, is permanent and irreversible.

In a proof-of-principle study published online in Proceedings of the National Academy of Sciences, the researchers have identified an antiviral small molecule that is effective against numerous viruses, including HIV-1, influenza A, filoviruses, poxviruses, arenaviruses, bunyaviruses, paramyxoviruses and flaviviruses. These viruses cause some of the world's deadliest diseases, such as AIDS, Nipah virus encephalitis, Ebola, hemorrhagic fever and Rift Valley fever.

http://www.eurekalert.org/pub_releases/2010-02/uoc--rf020110.php

Fluzone� High-Dose Approved for Elderly

Mixin — Tue Feb 02, 2010 11:28 am

Author: Mixin

Posted: Tue Feb 02, 2010 11:28 am

Fluzone High-Dose vaccine contains 60 mcg of hemagglutinin per strain of influenza virus in the vaccine as compared to 15 mcg of influenza virus hemagglutinin per strain of influenza virus in standard-dose Fluzone vaccine. Fluzone High-Dose vaccine is produced in the same production facility as Fluzone vaccine. Fluzone High-Dose vaccine is supplied as a single-dose, no preservative, prefilled syringe.

Side effects to Fluzone vaccines are soreness, pain and swelling at the injection site; fever, fatigue, headache and muscular pain. Other side effects may occur.

Full article: http://www.medicalnewstoday.com/articles/177661.php

USAF: Seasonal and Pandemic Flu Vaccination Data

gs — Tue Jan 26, 2010 6:10 pm

Author: gs

Posted: Tue Jan 26, 2010 6:10 pm

The results indicated that, as of January 2, an estimated 20.3% of the U.S. population (61 million persons) had been vaccinated, including

http://www.ncbi.nlm.nih.gov/pubmed/20094027?itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum&ordinalpos=28

Medicago's PanFlu Vaccine Provides 100% Protection in Mice

Mixin — Wed Dec 23, 2009 11:57 pm

Author: Mixin

Posted: Wed Dec 23, 2009 11:57 pm

Medicago reports positive Phase I results for its avian flu pandemic vaccine

The Phase I study was designed to investigate the safety of the Company's H5N1 alum-adjuvanted pandemic vaccine candidate and to provide an initial indication of the immune response. A total of 48 healthy volunteers between the ages 18 to 60 received two doses of either Medicago's vaccine at doses of 5, 10 or 20 micrograms (mcg) or a placebo. No serious adverse events were reported during the trial and the vaccine was found to be well tolerated at all three dose levels. Local site reactions were mild and the incidence of systemic side effects was comparable between the H5N1 vaccine groups and the placebo. As planned in the initial design, adverse event monitoring will continue for six months after administration of the second vaccine dose. The trial was conducted at the Vaccine Evaluation Center of McGill University in Montreal, Canada, under the supervision of Dr. Brian Ward.

Preliminary results showed that 81% of immunized subjects developed an immune response against the H5N1 virus after the second immunization. A four-fold increase in HI titers from baseline in 58% of subjects was observed in the 20 mcg group. HI titers greater than 1:40 were developed in 50% of the subjects in the 20 mcg group. The H5N1 vaccine also induced the production of antibodies cross-reacting with two other strains of H5N1 Avian Influenza suggesting Medicago's vaccine potential for cross-protection.

"Results at these lower dosage levels have not been reported for an H5N1 vaccine manufactured with a novel vaccine manufacturing technology," said Nathalie Landry, VP Product Development of Medicago. "H5N1 vaccines are poorly immunogenic in humans and are known to require repeated administrations with an adjuvant to elicit an immune response at low doses."

Full results of this trial will be submitted for publication in a scientific journal and will be available in the coming months. Based on these results, Medicago will proceed with a Phase II clinical trial, expected to commence during the first half of 2010.

About Medicago's pandemic flu vaccine candidate

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.

FDA-approved H5N1 influenza vaccines in the United States require two 90-microgram doses, administered at least four weeks apart to achieve appropriate level of antibodies in 44% of vaccinated individuals. Because Medicago's technology requires the genetic sequence of a viral strain and not the live influenza virus, vaccines can 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.

PR release: http://www.genengnews.com/news/bnitem.aspx?name=71637537

All Vaccines Under Development

Mixin — Mon Dec 14, 2009 11:00 am

Author: Mixin

Posted: Mon Dec 14, 2009 11:00 am

One recombinant subunit formula, Protein Sciences Corp.'s FluBlok, has completed phase 3 trials and has been submitted to the FDA in a biologics license application. Novavax has completed a phase 2 trial in Mexico of a vaccine containing virus-like particles and has enrolled 467 participants in a phase 2a trial in the United States.

(Separately today, NIAID announced that it has completed enrollment of 20 participants in a phase 1 safety trial for a DNA vaccine for pandemic H1N1 flu, developed at NIH's Vaccine Research Center.)

See also:

Dec 11 "HHS Science Seminar for Media: Advances in Influenza Vaccine Technologies"
http://videocast.nih.gov/

Dec 11 NIAID statement "NIAID Testing Candidate DNA Vaccine for 2009 H1N1 Influenza"
http://www3.niaid.nih.gov/news/newsreleases/2009/CandidateDNAvaccine.htm

pH1N1 Vax Ingredients

Mixin — Fri Dec 04, 2009 2:30 pm

Author: Mixin

Posted: Fri Dec 04, 2009 2:30 pm

What Glaxo's Pandemrix contains:
Active substance:
Split influenza virus, inactivated, containing antigen* equivalent to: A/California/7/2009 (H1N1)v-like strain (X-179A) 3.75 micrograms** per 0.5 ml dose
*propagated in eggs
** expressed in microgram haemagglutinin
Adjuvant:
The vaccine contains an adjuvant - AS03 to stimulate a better response. This adjuvant contains squalene (10.69 milligrams), DL-a-tocopherol (11.86 milligrams) and polysorbate 80 (4.86 milligrams).
Other ingredients:
The other ingredients are: polysorbate 80, octoxynol 10, thiomersal, sodium chloride, disodium hydrogen phosphate, potassium dihydrogen phosphate, potassium chloride, magnesium chloride, water for injections

What Novartis's Focetria contains:
Active Substance:
Influenza virus surface antigens (haemagglutinin and neuraminidase)* of strain: A/California/7/2009 (H1N1)v like strain (X-181) 7.5 micrograms** per 0.5 ml dose
* propagated in eggs
** expressed in microgram haemagglutinin.
Adjuvant:
The vaccine contains an adjuvant - (MF59C.1) to stimulate a better response. MF59C.1 is an oil/water emulsion containing 9.75 mg squalene, 1.175 mg polysorbate 80 and 1.175 mg sorbitan trioleate in a citrate buffer. Quantities are expressed per 0.5 ml vaccine dose.
Other Ingredients:
The other ingredients are: thiomersal (multidose vial only), sodium chloride, potassium chloride, potassium dihydrogen phosphate, disodium phosphate dihydrate, magnesium chloride hexahydrate, calcium chloride dihydrate, sodium citrate, citric acid and water for injections.

What Baxter AG's Celvapan contains:
Active substance:
Whole virion influenza vaccine, inactivated, containing antigen of pandemic strain*: A/California/07/2009 (H1N1) 7.5 micrograms** per 0.5 ml dose
* propagated in Vero cells (continuous cell line of mammalian origin)
** haemagglutinin
Other ingredients:
The other ingredients are:
trometamol, sodium chloride, water for injections, polysorbate 80.

See each label here: http://www.emea.europa.eu/

Tracking Vaccine Safety

gs — Fri Dec 04, 2009 10:23 am

Author: gs

Posted: Fri Dec 04, 2009 10:23 am

My summary:
reports and "reactions" per million vaccinations (deaths,cause unclear):
Celvapan:~20,+50,(~0.5)
Focetria:305,1162,(2.7)
Pandemrix:404,1100,(10)
Tamiflu:70,100,(14)

Novel Intranasal Nanoemulsion Vaccine Adjuvant

Mixin — Wed Dec 02, 2009 8:39 pm

Author: Mixin

Posted: Wed Dec 02, 2009 8:39 pm

Press Release

Novel Intranasal Nanoemulsion Vaccine Adjuvant Also Effective by Subcutaneous and Intramuscular Injection

NanoBio Corporation today announced positive results from studies in mice in which immune responses were evaluated following administration of 5�g doses of recombinant H5N1 pandemic flu antigen combined with the company's novel nanoemulsion vaccine. These studies are unique because the adjuvant was administered for the first time by subcutaneous (SC) and intramuscular (IM) injections. The mice that received either SC or IM H5 antigen combined with nanoemulsion had maximal immune responses at least a 1000 fold higher than control animals that received the same antigen IM without the nanoemulsion adjuvant. SC and IM administered NanoBio adjuvanted vaccines should share many of the advantages, including antigen-sparing properties, previously demonstrated in studies where the adjuvant was administered intranasally.

It is encouraging that these strong immune responses were achieved without evidence of significant irritation or inflammation, which could differentiate these IM vaccines from currently approved IM adjuvants,...

Earlier this year, the U.S. Food and Drug Administration (FDA) approved the company's Investigational New Drug (IND) application for the Phase 1 clinical study of NB-1008, a seasonal influenza vaccine administered via a nasal dropper. The Phase 1 study is ongoing.

Full story: http://www.tmcnet.com/usubmit/2009/12/02/4511768.htm