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| Overview | Pre- & Clinical Results | Second Generation – Multimeric Vaccine | ||||||||||||||||
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Efficacy in Young and Aged Mice In studies performed at the Weizmann Institute of Science, young and aged BALB/c mice were vaccinated with a mixture of recombinant flagella consisting of the three influenza B- and T-cell epitopes. The immunized mice were protected against a sub-lethal infection with the live virus. Over 90% reduction in virus burden in their lungs was observed (Figure 1). Immunization was proven effective against several other tested virus strains (H2N2, H3N2) (Table 1).  Figure 1. Protection of young and aged mice from viral challenge following immunization with the triple construct of flagella expressing the three influenza epitopes. In both age groups, a significant reduction (P<0.05) of the virus was observed in the vaccinated versus the control groups. Table 1: Cross protective immunity induced by a vaccine, comprising of 3 influenza murine epitopes, expressed within flagellin. The virus titer was evaluated 1 month after the last booster
The “Humanized Mouse” Model The "humanized mouse” model consists of irradiated mice radio-protected with SCID bone marrow and transplanted with functional human lymphocytes which are not rejected due to the irradiation. This model enables the simulation of the human immune response by engraftment of human PBMCs (peripheral blood mononuclear cells comprising both B and T lymphocytes) in the mice following destruction of the mice immune system by irradiation. Following intranasal immunization of the "humanized mouse” with the mixture of recombinant flagella, both B and T lymphocytes were detected by FACS analysis in the lungs of the chimera. Upon infection, the viral titer in the lungs of the vaccinated mice was reduced by 99%, in comparison to the control group. The vaccine confirmed cross-strain protection, i.e., it was effective against different strains of the virus (H1N1, H2N2 and H3N2) (Figure 2).  Figure 2: Significantly reduced (99.9%) viral load in lungs of “humanized” mice vs control. Int. Immunol. 1999, vol. 11(7) pp 1043-51. Long Lasting Protection The experimental results described above indicate that our epitope-based vaccine leads to efficient cross-strain and long lasting protection. In one of the experiments in which the long lasting protective effects were evaluated mice were challenged 7 months post vaccination. The average life span of mice is about 24 months thus we estimate that in humans the vaccine will have a protective effect for at least 3 to 5 years.  Figure 3: 100% survival of vaccinated mice from lethal challenged seven months after vaccination. Vaccine. 1996, vol. 14 (1) pp 85-92. Efficacy against Avian Flu (H5N1) In light of the growing concerns regarding the potential pandemic Avian Flu, BiondVax evaluated the protective effects of our universal influenza vaccine against the highly pathogenic H5N1 Avian Flu strain. The evaluation has been performed in vivo in a Bio Safety Level 3 facility*. The one vaccine formulation was administered intranasally or intramuscularly to transgenic mice that were then challenge with a LD80 lethal dose of a highly pathogenic H5N1 avian influenza strain. Survival level of the immunized mice via both routes was over two folds higher than the survival of the control group. In addition, the mortality in the immunized group was delayed as compared to the control group. Serum of immunized rabbits was tested in ELISA for its ability to recognize this H5N1 virus. The data demonstrate a dose related response, showing a significant elevation of H5N1 specific Ab response. The safety of the first generation epitope-based vaccine within flagellin was evaluated in a Phase I clinical trial. At a safe dose, with a low concentration of influenza epitopes, cross-reactive immunological responses specific to the influenza viruses were found, demonstrating the protective potential of a vaccine based on these epitopes. Nevertheless, due to the appearance of mild side effects possibly attributed to the flagellin, the company decided to discontinue the trial and re-focus its development efforts on the Multimeric, non-flagellin based vaccine. *The work was done in collaboration with Dr. Perk and his team from the Kimron Veterinary Institute, Israel. |
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