UK firm starting human trials on a therapeutic vaccine

[Cosmicdancer]

Not sure if info about this vaccine has been posted before.  It's a small UK company that is starting Phase 1b human trials soon on a therapeutic vaccine that targets the portion of hiv that doesn't mutate.  They have developed a hope to have interim results by December, 2009 and final results by June, 2010.  Let's hope their approach works.

HIV News
BioWorld Today July 6, 2009
By Jennifer Boggs

Assistant Managing Editor

The ultimate goal in HIV/AIDS work is a vaccine that can prevent HIV infection, yet the virus' wicked mutations and rapid variability have stymied progress at nearly every turn, so much that the AIDS Healthcare Foundation last year sought to curtail federal spending on the vaccines effort.

Yet UK firm PepTcell Ltd., unfazed by those past failures, is forging ahead with its own HIV vaccine approach designed to target specifically those regions of the virus that remain unchanged from variant to variant. It's a similar line of attack attempted by Whitehouse Station, N.J.-based Merck & Co. Inc.'s V520 T-cell vaccine, which failed Phase II studies in 2007, but with a couple of distinct differences, said PepTcell CEO Gregory Stoloff.

First, Merck's vaccine used an adenovirus - an inactivated version of the cold virus - as a delivery vehicle. Second, it delivered whole proteins, which include both the variable proteins and the conserved proteins, he said.

But it's the conserved proteins that are the crucial targets, making up the base of the virus that stays the same regardless of mutation and variation.

There are more variable proteins than conserved proteins on a cell's surface, meaning a vaccine that hits both triggers a stronger T-cell response against the variable proteins, which can change and mutate rapidly, rendering that response ineffective. Meanwhile, that distraction leaves a smaller herd of T cells available to go after the conserved proteins, "but it's not enough to defeat the virus," Stoloff said.

"These viruses have learned to be tricky," he told BioWorld Today. "You cannot deliver the full proteins because the immune system is fooled."

PepTcell's technology - the particular mechanism the firm is holding close to the vest - aims to quickly find the conserved regions on the virus cells. "No one has done this before," Stoloff said. Without the firm's platform, breaking down the proteins into their individual parts "would take a very long time."

By taking aim at specific conserved proteins, PepTcell's HIV vaccine can mobilize the army of T cells against the right target, with enough of a response to really deal with the viral load, he added.

It also works as both a T-cell and a B-cell vaccine, so it attacks the virus as it travels and prevents it from replicating once it enters the cells.

The bigger market - and more desperate need - is for a prophylactic vaccine, but a preventive study in healthy volunteers considered high risk for contracting HIV is far too costly for a small biotech. So PepTcell is starting out on the therapeutic side, having gained approval earlier this month for a Phase Ib proof-of-concept trial in the UK, testing the vaccine in recently diagnosed HIV patients.

"If we can vaccinate newly diagnosed HIV patients" who still have T-cell counts in the 500 to 800 range, they should "still have a strong enough immune response," Stoloff said.

Patients will be administered the one-shot vaccine in one of four doses - low dose with or without adjuvant or high dose with or without adjuvant - and be monitored for six months to see whether their viral loads decrease. Investigators also will be counting T cells, hoping to reach that 1,000 T-cell mark, Stoloff said.

The company anticipates an interim analysis in December, with final results by June 2010, though they could come sooner, depending on how quickly the trial is able to recruit patients.

If data are positive, PepTcell then plans to seek a large pharma partner to carry development forward.

Later this year, the company also plans to move into Phase Ib testing with its influenza vaccine. As with its HIV work, PepTcell was able to find conserved regions on the flu virus that in preclinical studies demonstrated protection in animals from any flu strain, including pandemic strains. The upcoming clinical trial will involve administering the vaccine to volunteers and then challenging them with flu strains. Pending positive results from that trial, "we'll hold discussions with partners," as well as with government entities to "see about getting fast-track [status] for pandemic use," Stoloff said.

PepTcell has an earlier-stage product in breast cancer, as well as a vaccine that is being designed to target the mosquito saliva to attack all diseases carries by the insect, such as dengue fever, malaria and West Nile virus. "So it's similar to the HIV and flu vaccines, except in this case, we're targeting the conserved regions in the carrier rather than the disease," he said.

The firm also has gained some other products via acquisitions "to spread the risk," Stoloff said. Those include programs to reprofile existing drugs in respiratory and inflammatory indications.

PepTcell, of High Wycombe, UK, was founded about six years ago by Stoloff, who had spent 20 years in the investment banking business before returning to science. But Stoloff's financial experience has come in handy.

The firm, which initially was funded by Stoloff and private money from several "high net worth individuals," managed to capture enough funding in its only fundraising round three years ago to get "at least five products through the end of Phase II," Stoloff said.

"We raised the money in one go, instead of having to come back to the market again and again," he added, "so we haven't been caught" by the current recession.

And the firm has kept costs down by running "a very tight ship," he said. PepTcell operates with a total of 12 employees and outsources much of its work.
 
<< Copyright ©2009 Thomson BioWorld, All Rights Reserved.>>

http://www.vircolab.com/about-virco/hiv-news?actv_news_latest_news_id=795

[J220]

Well it's certainly ambitious...let's hope they have something up their sleeve with their technology. Thanks for posting this.

[Cosmicdancer]

Here's a little more info about this vaccine from a press release a couple of weeks ago.  They mention very good results to date, but it's not clear if it's human or non-human subjects.

http://www.bioportfolio.com/biotech_news/PepTcell_5.htm

PepTcell to Start Phase Ib Clinical Trials for Novel HIV Vaccine
High Wycombe, UK – 24 June 2009 PepTcell Ltd. an immunology company with a focus on the development of vaccines for the prevention and treatment of infectious diseases, announced today that it has received approval from the MHRA to commence a Phase 1b clinical trial for its novel HIV vaccine in the UK.

PepTcell’s HIV-v vaccine offers new hope in the treatment and protection of HIV as it is the first vaccine to use a new approach for preventing and treating HIV by generating both a very strong B-cell and T-cell response from the immune system against regions of the virus that do not change from variant to variant. These unique features mean that the vaccine can be used to both treat people in the early phase of HIV infection and to protect people from getting the virus in the first place.

Wilson Caparros Wanderley, Chief Scientific Officer of PepTcell, says: “Based on results to date the vaccine produces a very strong response from both arms of the immune system after a single immunisation, even without adjuvant. The response is sufficient to enable the immune system to target and kill human cells infected with the virus and with different variants of the HIV virus.”

The development of an effective vaccine against HIV has been extremely difficult, as HIV constantly mutates, changing how it appears to the immune system. The PepTcell HIV-v vaccine is innovative in that it has been designed to specifically target the key conserved regions of the virus, which are not subject to regular mutation. Its design has significant advantages over other vaccines in that it only delivers those specific parts of the viral proteins that are important in the immune response rather than whole proteins which can trick the immune system in to remembering the wrong parts. The immune system will thus learn to recognise those regions within HIV proteins that are highly conserved and hence present in all different strains of this highly variable virus.

Gregory Stoloff, CEO of PepTcell, says: “This vaccine has been designed after taking into account all the lessons learnt from the prior excellent work undertaken in this field, has employed the latest theories in the understanding of the immune system and the most up to date chemical manufacturing processes available. Therefore, this vaccine has the best chance of any previous attempt to provide the solution that has evaded us to date.

The Phase Ib trial will involve 55 HIV positive volunteers, and will assess both safety and tolerability as well as the effectiveness of the vaccine by monitoring blood levels of the virus and CD4+ T-cell count, an immune cell which is specifically infected with HIV. The trial is expected to run for a year. The multi centre trial will be conducted at a number of HIV units in the UK. Details of the trial will be published at www.clinicaltrial.gov.uk 

Stuart Robinson, Head of Business Development at PepTcell says: “This vaccine is an opportunity to change the treatment landscape of HIV infection. The clinical trial being undertaken will vaccinate people in the early phase of HIV infection and monitor the effects on viral load and CD4+ count, both key markers of the progression of HIV disease.”

PepTcell's HIV-v vaccine can be quickly, easily and cost-effectively manufactured. The vaccine components are made synthetically thus allowing for increased purity and more efficient dosing of the vaccine compared to vaccines obtained or delivered via genetically modified organisms. Furthermore, the vaccine remains stable at a range of temperatures making it a viable and credible option for clinical use, not only in developed countries, but also in developing countries where large scale cold storage and distribution are not always available.

[newt]

"If we can vaccinate newly diagnosed HIV patients" who still have T-cell counts in the 500 to 800 range, they should "still have a strong enough immune response," Stoloff said.

We live in hope

I note the media CD4 count on diagnosis in the uk is around, erm, 300

- matt

[Inchlingblue]

We live in hope

I note the media CD4 count on diagnosis in the uk is around, erm, 300

- matt

Yes but that would presumably rise for many (the majority?) when effective HAART kicks in, which they should mention, since these vaccines are not only meant for the treatment-naive (or are they?).

Dr. Kang's therapeutic vaccine, discussed in another thread, is also to be tested on those with minimum 500 CD4s. It stands to reason that any therapeutic vaccine that aims to elicit an immune response would require a minimum level of immunocompetence.  

It remains to be seen if these will work at all (*fingers crossed*) and it makes sense that for the purposes of clinical trials they would want to ensure the best possible results by using 500 as a lower limit threshold but it's possible that if they do work, they might still work for those with <500 CD4s.

[brazilianman]

hello, I'm from Brazil and I like the forum on anti-ps is a good theory. I would like to know what the strength of the forum to ask for drug companies on research? much is spoken but not proven. vrx496? pro 140? Anybody know about this? sorry bad English.


Antibody specificities associated with neutralization breadth in plasma from HIV-1 subtype C infected blood donors

[brazilianman]

Hello, me again, I would put the email of dr. Sudhir.Paul @ uth.tmc.edu. that the abzymes. could ask him why does not Bill Gates Foundation? seems more a case of false advertising.

[Inchlingblue]

This is "still recruiting participants," oy vay.

LINK:

http://www.clinicaltrials.gov/ct2/show/NCT01071031?term=hiv&rank=3