Anybody knows about this HBSag Vaccin coming on 2014.
the thérapeutique vaccine made by Transgene against l’hépatite B chronique utilise an adénovirus
recombinant type 5 non réplicatif, carrying the séquence of many antigènes spécifiques (Core,Enveloppe et Polymérase) du génotype D de l’HBV.
The vaccine activate and/or stimulate theT cells fonction and capables of contrôling the réplication and elimination of HBV.
I don't think this therapeutic vaccine for HBV is even in clinical trial yet. So I think it becoming available in 2014 is impossible.
China had experienced two failures in its developments of a therapeutic vaccine for HBV. One completed Phase 3, the other Phase 2, both with unsatisfactory results. There are several DNA vaccines in pre-clinical studies. Only human clinical trials can show whether they are effective or not.
3:30 PM - 3:45 PM
33. TG1050, a viral-vector based immunotherapeutic designed to treat chronic hepatitis B induces immune responses with properties similar to those displayed by HBV resolving patients and has an early antiviral effect in a HBV tolerant model
Perrine Martin; Clarisse Dubois; Emilie Jacquier; Alexei Evlachev; Houda Boukhebza; Sarah Dion; Maryline Mancini-Bourgine; Ophélie Godon; Annie Findeli; Yasmin Schlesinger; Renée Brandely; Jean-Baptiste Marchand; Thierry Menguy; Nathalie Silvestre; Marie-Louise Michel; Genevieve Inchauspe
By itself, therapeutic vaccines provide little chance to clear the surface antigen, as has been shown many times now.
For example Marie Louise Michel, the senior scientist behind this one has previously worked on a DNA vaccine with up to phase II trials, for about 10 years, relentlessly pursuited. In the end absolutely no results...
the reaons are obvious to the one who understands how this approach can or cannot work.
BTW at the AASLD there will be a phase III trial result presentation of a combo surface antigen and core vaccine, both parenteral as well as mucosal.
In the Gambias, at the British Tropical Insitute, a phase II trial of a combo construct of the extremely immunogenic modified Ankara poxvirus and the HBV surface/core epitopes has been performed.
Painful lesions were generated, but the DNA levels barely moved downwards.
the only practical use that can be reasonable envisioned even for the best of these vaccines is to give a further push to an immune response already in motion, as in patients with a low surface antigen level, or to maintain patients low after Replicor therapy, in the SVR mode.
The biopharmaceutical company Transgene subsidiary of Institut Mérieux, said Monday it has achieved promising results in preclinical tests TG1050 its therapeutic vaccine against chronic hepatitis B and now provide an early test of man "from 2014 ".
The results of the TG1050 molecule were presented last week in Amsterdam at the EASL conference ("European Association for the Study of the Liver"), the European standard for liver disease, said Transgene in a statement.
The new data "confirm the ability of TG1050 to trigger a response (...) specifically directed against the hepatitis B virus (HBV) that persists over time," says Transgene.
"We (...) hear, from 2014, make the first administration in humans TG1050," said the CEO of Transgene Philippe Archinard, said in the statement.
"Compared to antiviral treatment with immunotherapy should significantly increase the cure rate of patients with chronic hepatitis B," said Dr. Fabien Zoulim, medical director of liver Department of Civil Hospitals of Lyon, said in the statement.
It offers "new hope of treatment duration is limited in time," says the specialist.
According to the World Health Organization (WHO), 350 million people worldwide are affected by chronic hepatitis B infection.
This disease is responsible each year a million deaths.
Transgene secondly presented at the same conference "clinical trial data encouraging" the Phase II trial of its TG4040 product in the treatment of chronic hepatitis C, according to another statement.
This test (HCVac) combined administration TG4040 with standard treatment with interferon.
Transgene study now "different opportunities for future clinical developments TG4040", considering the test continued without interferon, said Mr. Archinard.
"We should be able to assess TG4040 in regimens without interferon and including new direct-acting antivirals when they have been approved," said the CEO of Transgene, said in the statement.
Based near Strasbourg, Transgene 55% owned by Institut Mérieux.
TITLE: TG1050, a viral-vector based immunotherapeutic designed to treat chronic hepatitis B induces immune responses with properties similar to those displayed by HBV resolving patients and has an early antiviral effect in a HBV tolerant model
AUTHORS (FIRST NAME, LAST NAME): Perrine Martin1, Clarisse Dubois1, Emilie Jacquier1, Alexei Evlachev1, Houda Boukhebza1, Sarah Dion3, 4, Maryline Mancini-Bourgine3, 4, Ophélie Godon3, 4, Annie Findeli2, Yasmin Schlesinger2, Renée Brandely2, Jean-Baptiste Marchand2, Thierry Menguy2, Nathalie Silvestre2, Marie-Louise Michel3, 4, Genevieve Inchauspe1
INSTITUTIONS (ALL): 1. Infectious Diseases, Transgene, Lyon, France.
2. Molecular Immunology, Transgene, Strasbourg, France.
3. U845, INSERM, Paris, France.
4. Virology, Institut Pasteur, Paris, France.
ABSTRACT BODY: Currently used small molecules aiming at treating chronic hepatitis B infection (CHB) rarely achieve cure. They do not recruit the immune system yet a strong inverse correlation is widely described between HBV-specific functional T cells and eradication of viremia in cohort studies. Thus, T cell driven immunotherapies represent an attractive novel treatment approach to CHB offering the likelihood of increasing cure rate.
We developed an immunotherapeutic, called TG1050, based on a non-replicative adenovirus serotype 5 vector encoding a unique fusion protein composed of a truncated Core, a modified Polymerase and HBsAg domains. TG1050 capacities to induce robust, multispecific, polyfunctional and long-lasting T cells were assessed in 3 naïve mouse models (HLA-A2 mice, BALB/c and C57BL/6J mice) following single or multiple subcutaneous injections. Induced immune responses were evaluated in blood, spleens and livers through IFNg ELISPOT, Intracellular Cytokine Staining, in vivo CTL assays, pentamers and memory markers staining. TG1050 ability to induce functional T cells in spleens and livers and its impact on viral parameters were assessed in a HBV tolerant mouse model based on a AAV (Adenovirus-Associated Virus) expressing the full length HBV genome.
In naïve mice, TG1050 induces high levels of T cells targeting Core, Polymerase and HBsAg domains. High frequencies of IFNg and/or TNFa producing T cells and vigorous in vivo cytolytic functions are detected in spleens and/or livers of immunized mice. Induced HBV-specific T cells are detected up to 10 months post-immunization in blood of mice injected once. These cells display an effector memory phenotype (CD44+/CD62L-) and markers of good recall potential (CD27+/CD43-). In the AAV-HBV tolerant mouse model, a single injection of TG1050 induces functional and long-lasting T cells producing IFNg, TNFa and IL2 both detected in spleens and livers in absence of ALT elevation. Interestingly, following a single injection of TG1050, a transient control of HBV viremia and HBsAg level was observed in blood within 2 weeks post-immunisation. Experiments are ongoing to analyse immunological and virological effects of multiple injections of TG1050 as well as longer follow-ups.
Overall, TG1050 is a unique targeted immunotherapeutic capable of inducing polyfunctional, multispecific, robust and long-lasting T cells targeting multiple epitopes from three major viral proteins. In a surrogate HBV tolerant model, it was possible to show an impact of TG1050 administration on a key virological parameter i.e. the level of circulating HBsAg. TG1050 has moved to GMP production.
Is TG1050 a DNA vaccine delivered by a viral vector? Since it is delivered by injection, what cells or cell types are expected to be infected by the viral vector and then express the expected antigens?
Or am I on the wrong tack altogether?
It is a viral vector encoding a fusion protein that contains the critical epitope regions of several HBV proteins. One would expect that dendritic cells and macrophages are infected, maybe even the liver, but unfortunately those details are not given.
Here is the long awaited result of the Cuban surface antigen plus core particle vaccine study, mucosal and subcutaneous. It looks fairly promising.
TITLE: A phase III clinical trial with a therapeutic vaccine containing both HBsAg and HBcAg administered via both mucosal and parenteral routes in patients with chronic hepatitis B
AUTHORS (FIRST NAME, LAST NAME): Sheikh Mohammad Fazle Akbar1, 4, Mamun A. Mahtab2, Salimur Rahman2, Julio Cesar Aguilar3, Yoichi Hiasa4, Shunji Mishiro1
INSTITUTIONS (ALL): 1. Department of Medical Sciences, Toshiba General Hospital, Tokyo, Japan.
2. Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh.
3. Clinical Trials , Center for Genetic Engineering and Biotechnology, Havana, Cuba.
4. Department of Gastroenetrology and Metabology, Ehime University Graduate School of Medicine, Toon, Japan.
ABSTRACT BODY: Background and aims: Lack of information is prevailing about scope and limitation of a therapeutic vaccine for chronic hepatitis B (1) that utilized multiple antigens; both HBsAg and HBcAg, (2) applied via multiple routes of administration: both mucosal and parenteral, and (3) conducted as a phase III clinical trial in same run in which a different arm received an established and commercially-available antiviral drug. Methods: A total of 160 patients with clinical, biochemical, and virological evidences of chronic hepatitis B were enrolled in a phase III clinical trial (Clinical Trials.Gov identifier NCT01374308) after receiving written consent of the patients and written permission of institutional review board (Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh). The patients were randomly assigned to receive either a therapeutic vaccine (HBsAg/HBcAg-based vaccine) or pegylated interferon (Peg-IFN). Seventy-five CHB patients completed the therapeutic schedule of immunization with 100 microgram of both HBsAg and HBcAg (HBsAg/HBcAg) (Center for Genetic Engineering and Biotechnology, Havana, Cuba), once in every two weeks (5 vaccinations through only nasal route and followed by 5 additional vaccinations via both nasal and subcutaneous route). Seventy-six patients with CHB completed the treatment with Peg IFN (180 microgram, once weekly, subcutaneously for 48 consecutive weeks). Parameters of safety and therapeutic efficacy were checked during treatment period and also for 24 weeks after end of treatment (EOT). Results: Preliminary results evidenced the safety of HBsAg/HBcAg-based therapeutic immunization; no serious or severe adverse event was detected. Forty-six of 75 patients (61%) receiving HBsAg/HBcAg vaccine reduced the HBV DNA below 250 copies/ml (undetectable HBV DNA) at EOT and a similar proportion remain below 250 copies/mL at the end of 24 weeks of treatment-free follow up. Fifty-one of 76 patients (67%) receiving Peg-IFN reduced the HBV DNA level below 250 copies/mL at EOT, however, only 39% remain under the same level at 24 weeks after EOT during treatment-free follow up. ALT increases were not clinically symptomatic in patients receiving HBsAg/HBcAg vaccine and a generalized normalization of ALT values in the majority of patients at the EOT and 24 weeks of treatment-free follow up was recorded. Conclusions: A therapeutic vaccine therapy containing HBsAg/HBcAg represents a safe and efficacious therapeutic approach for CHB. This study inspired optimism that ongoing protocols of immune therapy against CHB may be improved by altering nature of antigens and route of administration.
Many thanks. It is just that the concept of viral vector rendered non-replicative and can also made to carry specially designed piece of DNA is pretty amazing to me.
I notice REP9AC will not be at the Liver Meeting.
The key aspect is the capacity of the vector to enter once and express the critical antigens with epitope processing for presentation on the surface of dendritic cells to docking Tcells of epitope specificity. No further replication of the vector is possible. It is like a Trojan horse approach to get the HBV epitopes to the needed cytosolic location, where they can enter the class I processing and presentation pathway.
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