Adjuvant may stretch swine flu vaccine supply
Greece, The Netherlands, Canada and Israel have ordered enough double doses of swine flu vaccine to inoculate their entire populations. "Pandemic vaccine orders put in by northern hemisphere countries stand at over one billion," a World Health Organization spokesperson told AFP.
Although just last month the WHO had tallied manufacturing capacity of 94 million doses per week starting in mid-October based on estimates from 25 drug companies, reality has hit: the major makers report delays and a new yield projection that is half or less of the original, the AFP reports.
That could be good news for specialty drug-maker Biosante, which just announced that its BioVant adjuvant increased the protective effect of vaccines for multiple flu strains, including a potential swine flu vaccine, yielding 100 percent protection from symptoms of illness. Its studies showed that both swine and bird flu vaccines fortified with BioVant may stretch supplies through the use of lower doses. Intranasal administration could provide more convenient and wider distribution during a flu pandemic.
Read more: http://www.fiercepharmamanufacturing.com/story/adjuvant-may-stretch-swine-flu-vaccine-supply/2009-08-19#ixzz0Ohj8V6Mk
ABOUT THE BIOVANT ADJUVANT:
An adjuvant is used to simulate the immune system and increase the body's response to a vaccine, without having any specific antigenic effect in itself.
The BioVant adjuvant can be administered intranasally, paving way for a more wider and convenient mode of distribution. The company noted that as the adjuvant enhanced the natural immune response to swine flu and other flu strains, BioVant may allow for availability of a greater number of lower-dose vaccines.
Michael Snabes, BioSante's vice president of clinical development stated, "The exciting prospect is that BioVant also may allow use of lower doses of H1N1 swine flu vaccines in order to stretch potentially limited vaccine supplies."
BPAX is currently trading up 27 cents or 13.78% at $2.23, on a volume of 3.7 million shares.
BioSante Pharmaceuticals, Inc. (OTC BB: BISP), Lincolnshire, Ill., has reported results of several studies demonstrating the superiority of its innovative calcium phosphate nanoparticulate (CAP) vaccine adjuvant and delivery system, BioVant (TM), compared to the only approved adjuvant, aluminum salts (alum). The company has also recently announced a cooperative research and development agreement (CRADA) with the U.S. Army to use the new technology in the development of biodefense vaccines.
In the reported studies, BioVant was combined with antigens from the Epstein-Barr virus (EBV), the Herpes Simplex-2 virus (HSV-2) and the Influenza virus (flu), in proprietary vaccine formulations developed by BioSante scientists. The studies, conducted in a series of animal models, were designed to evaluate the immune enhancement effects of BioVant compared to vaccines using alum.
In the study of EBV vaccines, the antibody (IgG) response was significantly higher for the BioVant-EBV vaccine than that of the alum-adjuvant vaccine. Similarly, in mice inoculated with the HSV-2 vaccine, the BioVant-HSV-2 vaccine elicited a substantially greater immune response than the alum-adjuvant vaccine. Both Th1 and Th2 T-cell responses occurred using the BioVant-HSV-2 vaccine, but the bias was towards a Th1 T-cell response. Furthermore, the BioVant-HSV-2 vaccine provided 100 percent protection after challenge with a lethal dose of live virus.
In the study of flu vaccines, the BioVant-flu vaccine induced an antibody response comparable to that of the alum-based vaccine while using only one percent of the amount of antigen contained in the alum-flu vaccine. These findings suggest BioVant is more potent than alum on a weight-for-weight basis, for the elicitation of virus-specific immunity. Similar advantages for BioVant are observed for bacterial vaccines.
"These study results indicate BioVant may be more potent on a weight-for-weight basis and a safer alternative to alum for immune enhancement of vaccine-induced responses," said Stephen M. Simes, president and chief executive officer of BioSante. "Theoretically, the smaller the amount of virus antigen and adjuvant that must be incorporated into a vaccine, the less likely a patient will experience an adverse reaction."
An adjuvant is a substance that, when added to a vaccine, enhances the vaccine's effect by stimulating an immune system response. Aluminum salt derivatives, such as alum, currently are the only adjuvants approved by the Food and Drug Administration (FDA) for use in the United ...
MATRIX PROTEIN M1 vaccine:
A DNA plasmid expressing both the influenza viral matrix protein (M1) and hemagglutinin (HA) (pHA/M1) as a potential vaccine candidate was investigated. Vaccination with pHA/M1 double insertion plasmids not only induced HA-specific protective antibodies, but also elicited HA and M1-specific CD8 T cell responses. Mice immunized with pHA/M1 dual expressing plasmid showed enhanced HA inhibition titer and increased CD69(+) CD8alpha(+) T cell response compared to groups that received either the vector or a mixture of both pHA and pM1 (pHA+pM1). Furthermore, pHA/M1 immunization resulted in improved protection against both homologous and heterologous challenges.
That is a novel idea, similar to the idea developed at Burnham Institute with their monoclonal antibody. In principle, it is a good idea.
BUT WHAT IS IT THEY ARE DOING: PAY ATTENTION:
Vaccine-delivery systems are generally particulate (e.g., emulsions, microparticles and liposomes) and have comparable dimensions to the pathogens, which the immune system evolved to combat. Increasingly more sophisticated delivery systems are being developed in which immunostimulatory adjuvants may be incorporated with the antigen. The rationale for this approach is to ensure that both the antigen and adjuvant are delivered into the same population of antigen-presenting cells. Enhancement of adjuvant activity through the use of micro- and nanoparticulate delivery systems is particularly exciting, as synergistic effects are often seen resulting in immune responses stronger than those elicited by the adjuvant or delivery system alone. Micro- and nanoparticles also offer the possibility of enhancement of their uptake by appropriate cells through manipulation of their surface properties. The next important step in the development of many of the experimental microparticle- and nanoparticle-based technologies will be evaluation of effectiveness in human trials.
And also recent, from our dear friend NOVARTIS of ill fame:
A comparison of anionic nanoparticles and microparticles as vaccine delivery systems.Hum Vaccin. 2008 Jan-Feb;4(1):44-9. Epub 2007 Aug 15.
Novartis Vaccines and Diagnostics, Inc., Emeryville, CA 94608, USA.
The objective of this work was to conduct an in vivo comparison of nanoparticles and microparticles as vaccine delivery systems. Poly (lactide-co-glycolide) (PLG) polymers were used to create nanoparticles size 110 nm and microparticles of size 800-900 nm. Protein antigens were then adsorbed to these particles. The efficacy of these delivery systems was tested with two protein antigens. A recombinant antigen from Neisseria meningitides type B (MenB) was administered intramuscularly (i.m.) or intraperitonealy (i.p.). An antigen from HIV-1, env glycoprotein gp140 was administered intranasally (i.n.) followed by an i.m. boost. From three studies, there were no differences between the nanoparticles and micro-particles formulations. Both particles led to comparable immune responses in mice. The immune responses for MenB (serum bactericidal activity and antibody titers) were equivalent to the control of aluminum hydroxide. For the gp140, the LTK63 was necessary for high titers. Both nanoparticles and microparticles are promising delivery systems.
What is LTK63?
The Acquired Immune Response to the Mucosal Adjuvant LTK63 Imprints the Mouse Lung with a Protective SignatureElaine Tritto*, Alessandro Muzzi*, Isabella Pesce*, Elisabetta Monaci*, Sandra Nuti*, Grazia Galli*, Andreas Wack*, Rino Rappuoli*, Tracy Hussell and Ennio De Gregorio1,*
* Novartis Vaccines and Diagnostics, Siena, Italy; and Kennedy Institute, Imperial College of Science, Technology and Medicine, London, United KingdomLTK63, a nontoxic mutant of Escherichia coli heat labile enterotoxin (LT), is a potent and safe mucosal adjuvant that has also been shown to confer generic protection to several respiratory pathogens.
So what they did, ALSO IN THE US, is give HIV intranasally to mice, enrobed in an enterotoxin mutant envelope, for added immune response ; the results were no different from alum. AND they had to give an immune boost following that: TWO DOSES ALTOGETHER.
So, in summary, WHAT DID NOVARTIS TEST TWO YEARS AGO?
AN INHALED VACCINE in nanoparticles- USING HIV enrobed in mutated enterotoxin, THAT REQUIRES TWO DOSES to be effective...the second one being an intramuscular injection.
1. These calcium phosphate nanoparticles are being developed as part of a BIOWEAPONS SYSTEM PROGRAM
2. THE SUBSTANCE IS TOXIC TO LUNGS IN UNKNOWN QUANTITIES
3. IT WAS ONLY TESTED ON LAB ANIMALS, and they need to test the effectiveness of their bioweapons in human trials.
4., according to the company's own words in 2003, ITS EFFECTIVENESS IN INFLUENZA VIRUS was then COMPARABLE TO ALUM...
...things could have changed since then....
ALUM DOES NOT WORK WITH INFLUENZA VIRUS! That is according to a recent study.
See: Published: 05/29/2009
Vaccine Adjuvants: Scientific Challenges and Strategic Initiatives
Ali M. Harandi,1 Gwyn Davies,2 Ole F. Olesen 3
.....Thus, the development of safe and potent immunologic adjuvants and delivery systems that can enhance and direct vaccine-specific immunity is needed. With few exceptions, aluminum salts (alum) are currently the only vaccine adjuvant approved for human use worldwide. Alum is effective at generating a strong antibody response to an antigen with a bias towards a Th2 type of immune response, and, as such, has been widely and effectively used in many vaccines, such as tetanus, diphtheria, pertussis and poliomyelitis vaccines. The mechanism of immunopotentiation by alum involves inflammation and recruitment of antigen-presenting cells, retention of antigen at the injection site, uptake of antigen, dendritic cell maturation, T-cell activation and T-cell differentiation. Although alum adjuvants have proved their efficiency in a large number of applications, some limitations of alum have been reported. Thus, alum failed to confer satisfactory increase of the immune response in certain vaccines, such as typhoid fever and influenza vaccines. Reports have also demonstrated that alum displays limited ability to raise high antibody titers against small-size peptides. Importantly, alum is a poor enhancer of cytotoxic T-cell immunity and Th1 responses, the type of immunity needed to combat several life-threatening infections and cancers.
So what is it I am missing?
WHAT WOULD BE THE PURPOSE OF ADDING THIS TO AN H1N1 VACCINE, if it is INEFFECTIVE as an antigen boost?
Has the effectiveness increased in the last 6 years?
It is possible that their SPECIFIC formulation of M1 antigen with Calcium nanoparticles works. It IS possible.....
However, knowing that
It is being developed as part of a BIOWEAPONS LAB,
and that it is highly experimental at this stage, having NEVER been tested on HUMANS,
and it is a KNOWN FACT - see my article just yesterday about this topic - that BIOWEAPONS LABS REPEATEDLY TEST THEIR WEAPONS ON UNINFORMED SUBJECTS...
At the same time...
...GENE DELIVERY TO HUMAN CELLS IS BEING TESTED.
WHAT EXACTLY ARE THEY TRYING TO LEARN IN THIS PROCESS? WHAT GENES ARE THEY TRYING TO INTRODUCE TO HUMAN NUCLEUS MATERIAL?
Pay attention to this article:
Adverse effects of viral vectors, instability of naked DNA, cytotoxicity and low transfection of cationic lipids, cationic polymers and other synthetic vectors are currently severe limitations in gene therapy. In addition to targeting a specific cell type, an ideal nonviral vector must manifest an efficient endosomal escape, render sufficient protection of DNA in the cytosol and help provide an easy passage of cytosolic DNA to the nucleus. Virus-like size calcium phosphate nanoparticles have been found to overcome many of these limitations in delivering genes to the nucleus of specific cells. This review has focused on some applications of DNA-loaded calcium phosphate nanoparticles as nonviral vectors in gene delivery, and their potential use in gene therapy, as well as highlighting the mechanistic studies to probe the reason for high transfection efficiency of the vector. It has been demonstrated that calcium ions play an important role in endosomal escape, cytosolic stability and enhanced nuclear uptake of DNA through nuclear pore complexes. The special role of exogenous calcium ions to overcome obstacles in practical realization of this field suggests that calcium phosphate nanoparticles are not 'me too' synthetic vectors and can be designated as second-generation nonviral vectors for gene therapy.
Prof. Maitra bio:
Career HighlightsHe is now Adjunct Professor in the Department of Biological Chemistry of Indian Association for the Cultivation of Science, Kolkata, India where he is going to join soon as INSA Emeritus Professor also. Professor Maitra is associated with the Nanotechnology programme of the country as various capacities. Currently he is Visiting Scientist at the Department of Pathology Johns Hopkins Medical Institute, Baltimore, USA where he developed oral delivery systems for poorly water soluble anticancer drugs.
Professor Maitra has been invited for three months as an Adviser of Nanotec Centre of Thailand Government where he would join soon. The earlier President of India, Dr APJ Abdul Kalam mentioned the contributions of Professor Maitra in Nanotechnology research in the country in his several talks. About a dozen of Universities in India who are going to open Nanotechnology Centre have appointed Prof Maitra as member of their Advisory Boards.
Amarnath Maitra (born in February 1943) received his M.Sc. in Chemistry from Calcutta University in 1964 and Ph.D. from Jadavpur University, Kolkata in 1971. His Ph.D. topic was on Boron and Silicon Heterocycles. Prof Maitra joined the University of Delhi in 1972 and did research in the areas of metal corrosion, passivation and inhibition, NMR relaxation and self diffusion , quadrupolar relaxation of electrolytic solutions and microemulsuions, structural studies of microemulsions by FTIR spectroscopy, dielectric spectroscopy and positron annhilation techniques, preparation of ultralow size nanoparticles using microemulsions as media such as high Tc Superconductors, Titanium Dioxides, Silver halides, and other ceramic nanoparticles.
Prof Maitra was invited as Visiting Professor in Lund University (Sweden) in 1987 and in Basel University (Switzerland) in 1991.( home of NOVARTIS, DS)) He was also invited as Visiting Scientist at the laboratory of Prof D.O.Shah in U.S.A. in 1989 and under INSA exchange programme at the Polish Academy of Science, Krakow (Poland) in 1993 and at the School of Pharmacy, University of London in 2004.
MIT, Lankenau Institute Team Up on Positive Nanodelivery Study
Nanodelivery of medicines could be ready for human clinical trials in as little as a year, say researchers at MIT and the Lankenau Institute in the wake of the publication of a study on nano therapies for ovarian cancer.
"What we did was deliver DNA that basically tells cells to die. But it is only turned on in ovarian cells," said Dan Anderson of the Massachusetts Institute of Technology, who worked on the study published in the journal Cancer Research.
The research, a joint project from MIT and Pennsylvania's Lankenau Institute, used an "artificial virus" -- a biodegradable polymer that can get inside the cell and be absorbed by the body, in much the same way biodegradable sutures work. To form the nanoparticle, the polymers are mixed with a gene that produces a modified form of the diphtheria toxin that is only harmful to ovarian cancer cells.
MIT is working on nanoparticles as a safer alternative to viruses in making powerful new embryonic-like cells called induced pluripotent stem cells, or iPS cells.
CALCIUM PHOSPHATE NANOPARTICLES AS NON-VIRAL VECTORS FOR GENE THERAPY ( Prof. Maitra, currently in Baltimore)...
NANOPARTICLES USED TO INFECT MICE INTRANASALLY WITH AIDS ( by Novartis, who seems to have learned from this professor)...
All these tests are going on as we speak, and as they want to use that delivery method for H1N1 vaccine.
So what is going on here? Is this totally INNOCUOUS, is it meant as THERAPY? Or is it part of a BIOWEAPONS PROGRAM TESTING CAMPAIGN?
OR COULD IT BE "DUAL USE"??
FOR SURE, EVEN IF IT WERE 100% INNOCUOUS, IT WOULD STILL BE 100% EXPERIMENTAL IN HUMANS.
And knowing what we know today about Novartis and their "innocuous" vaccines...
...I WOULD BE VERY, VERY , SUSPICIOUS, KNOWING THE INTENT OF THE PTB, IN PARTICULAR OF WHO AND THE UN.
Only questions at this stage; no answer. But I am sure you are starting to see the problems :
DO NOT FALL FOR IT. DO NOT TAKE ANY NASALLY BASED INFLUENZA VACCINE at this stage, OR ANY PART OF ANY H1N1 VACCINE!
Additional benefits of CAP include (i) an insignificant IgE response, which is an important advantage over injection of alum compounds,
Calcium phosphate (CAP), aluminum compounds have been approved for human use in several European countries.［1］ Although effective in the enhancement of Th2 immune responses, aluminum compounds also produced severe local tissue irritation, induced no cell-mediated immunity, and elicited undesirable immunoglobulin E (IgE) responses.［2-5］ For these reasons, the application of aluminum compounds was limited.
AS FOR THE POOR OF THIS WORLD.........
Vaccine platform to aid in pandemic preparedness
Influenza vaccine production is the subject of an agreement between Neugenesis and the international nonprofit PATH. Under the agreement, Neugenesis will conduct proof-of-concept work to demonstrate the utility of its NeuBIOS protein production platform for making seasonal and pandemic influenza vaccine, according to an announcement.
The Neugenesis platform provides high-level expression of recombinant, multivalent, influenza virus antigens from the transformed filamentous fungus, Neurospora crassa. The company says the platform is "scalable, inexpensive, and can be upgraded with genes for new influenza variant antigens to produce new vaccines in weeks, rather than months." Under the PATH agreement, the NeuBios platform will be used to make non-infectious, non-replicating virus-like particles.
The platform will help PATH in its efforts to develop pandemic-response influenza vaccines that will be safe, effective, and affordable for distribution by public health systems in low-income countries.