Following up on a recent article, Overcoming the Hurdles to a Universal Flu Vaccine, I had the opportunity to discuss details about the efforts BiondVax is making toward this goal with their CSO Dr. Tamar Ben-Yedidia.
BiondVax appears to have the most advanced program toward providing an approved universal flu vaccine. They are currently in Phase II trials for their "Multimeric-001" (M-001) vaccine to be used in conjunction with the standard seasonal flu vaccine to boost its effect—a flu vaccine "primer".
However, BiondVax is also pursuing the same formulation of M-001 as a single stand alone general vaccine against all influenza strains. It has data showing that M-001 induces immune cells against several diverse flu strains. Why are they just currently pursuing approval of M-001 as a flu primer then, you might ask?
Easier Approval for Flu Vaccine Primer
BiondVax's strategy reflects the practical realities of bringing new therapeutics to market. The approval for a universal vaccine would be much more onerous and require much larger trial sizes to prove effectiveness than a medicine that enhances the effect of the seasonal vaccine. Dr. Ben-Yedidia pointed out that the universal primer application for M-001 enables BiondVax to both prove safety of the vaccine and generate revenue, so they have the resources and data to support approval as a standalone universal vaccine.
However, this brings up the question of how same formulation can both provide universal protection against multiple influenza strains and also improve the immune response of the standard seasonal flu vaccine. This dual capability stems from the way the M-001 vaccine was developed.
How Was BiondVax's Vaccine Developed?
BiondVax's vaccine development started with work done by Prof. Arnon's team at the Weitzman institute about 10 years ago. This is the same team that developed Copaxone for the treatment of Multiple Sclerosis, an autoimmune disease. The group, of which Dr. Ben-Yedidia was a member, analyzed genetic data collected by the NIH on over 10,000 viruses since the 1940s to identify epitopes that were common across multiple flu viruses. An epitope is a small part of the virus (or any antigen) that an antibody interacts with.
In addition to looking for epitopes common to multiple influenza strains, the lab also looked for ones with characteristics that induce an immune response of both the B-cell antibody producing side and the T-helper/killer cell part of the immune system.
What Is the M-001?
The M-001 vaccine is a recombinant protein comprising the top nine selected epitopes identified by Dr. Arnon's group as common to most flu viruses . Each epitope corresponds to a small piece of an influenza protein, and they can be mimicked by a peptide that has the same amino acid composition as the short protein fragment. As Dr. Ben-Yedidia describes it, the M-001 vaccine is simply "the peptides chained together like a necklace." Although the M-001 was designed almost 10 years ago, Dr. Ben-Yedidia said that they confirmed the epitopes identified for M-001 are still present in more recent variants of influenza so they appear well conserved.
In addition to stimulating a strong immune response, the engineered M-001 protein can be expressed bacterial which makes it very easy to produce. Dr. Ben-Yedidia noted that it just takes six week to generate a batch of the M-001 vaccine using standard laboratory techniques, in contrast to the egg-based production process used for standard flu vaccines which takes about 6 months.
Improves Response to Seasonal Vaccine and General Flu Immunity
It is actually the ability of the M-001 vaccine to activate the T-cells, as well as the B-cell antibody response, that enables it to function as a primer for the seasonal flu vaccine. M-001 stimulates production of T-cells so there are more of these cells present to produce a larger response when they are later exposed to antigens in the standard vaccine. The therapeutic protocol proposed by BiondVax would be to get one shot of M-001 primer, then 4 weeks later the seasonal flu shot.
Business Plans
BiondVax was founded in 2003 and raised about $3M when it went public on the Tel Aviv Stock Exchange in 2007. The company of just 14 people has maintained a sharp focus on flu vaccine development. Their target is to have M-001 approval by 2015 and are in discussions with the major flu vaccine providers, companies like Sanofi, Novartis, and GSK, to have integrated protocols that utilize M-001 with the seasonal flu vaccines, especially for high-risk populations such as the elderly and young children.
