VaxInnate's Universal Flu Vaccine Candidate Shown Safe and Immunogenic in Phase I Clinical Study

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VaxInnate's Universal Flu Vaccine Candidate Shown Safe and Immunogenic in Phase I Clinical Study

Study validates proprietary technology that could transform flu vaccine production

WASHINGTON--(BUSINESS WIRE)--A universal flu vaccine candidate that could end the need for annual flu shots and provide protection against seasonal and pandemic flu strains was well tolerated and immunogenic in a Phase I study that was presented at the joint 48th ICAAC/46th IDSA annual meetings here today.

This first clinical study of VaxInnate's M2e universal flu vaccine candidate also validates the Cranbury, NJ-based biotechnology company's novel approach to developing and producing flu vaccines, which is based upon a proprietary combination of toll-like receptor (TLR)-mediated immune enhancement and recombinant bacterial production of vaccine antigen.

"VaxInnate's M2e universal flu vaccine candidate has passed a critical initial test," said David Taylor, MD, Chief Medical Officer. "We're encouraged by these data, which demonstrate that the vaccine is safe and elicits potent immune responses at doses below a microgram of vaccine antigen, and does so without the use of conventional adjuvants."

Safety & Immunogenicity Established

The multicenter, double-blind, randomized, placebo-controlled Phase I study was designed to assess the safety and immunogenicity -- a patient's ability to generate an immune response -- of four doses (0.3, 1, 3 and 10 μg) of the vaccine candidate. The vaccine candidate is comprised of the ectodomain of the viral M2 protein (M2e) fused to the bacterial protein flagellin.

Sixty healthy young volunteers aged 18-49 were randomized to receive the vaccine candidate in dosages of 0.3 μg (6 subjects), 1.0 μg (18 subjects), 3.0 μg (6 subjects), 10 μg (14 subjects), compared to placebo (16 subjects), in two doses injected 28 days apart. Clinical and laboratory safety assessments took place 1 and 7 days after immunization; immune response to M2e and flagellin was assessed at 7, 14 and 28 days after each dose. Seroconversion was defined as a serum IgG anti-M2e antibody (µg/ml) value ≥ 0.174 and a four-fold rise in titer.

The 0.3 and 1.0 µg doses were safe and well tolerated in all subjects and immunogenic in 18 (75%) of 24 vaccinees after the first dose and 23 (96%) after the second dose. In the 1.0 µg group, the geometric mean M2e antibody concentration was 0.4 µg/ml after the first dose and 1.7 µg/ml after the booster dose. Immune responses to flagellin were also robust and did not appear to negatively affect M2e antibody responses from the booster dose. The two highest doses (3 and 10 µg) were associated with the presence of flu-like symptoms in some of the subjects.

Given the strength of the antibody responses and the absence of significant adverse reactions at the two lowest doses (0.3 and 1.0 μg), VaxInnate intends to continue development and clinical evaluation of the vaccine candidate at doses of 1.0 μg and less.

"In this trial, the M2e flu vaccine candidate was well tolerated and able to induce high antibody levels to M2e at 0.3 and 1.0 μg, the two lowest doses we studied," said primary investigator Christine Turley, MD, who is Director of Clinical Trials and Clinical Research at the Sealy Center for Vaccine Development, University of Texas Medical Branch (UTMB). "These results suggest that the M2e vaccine candidate could be a promising and much-needed new option for prevention or attenuation of influenza A disease."

UTMB and VaxInnate researchers are collaborating on a manuscript for submission to a peer-reviewed journal.

The trial was conducted at study sites in Galveston, TX and Lenexa, KS. It was supported by a $9.5 million grant awarded to UTMB by the Bill & Melinda Gates Foundation, for better control of influenza epidemics in the developing world.

Universal Vaccination Challenges

A universal influenza vaccine is one that would provide protection against all strains of seasonal and pandemic influenza A without requiring annual shots. Although universal vaccination has been proposed to improve vaccination coverage and prevent disease, there are no universal vaccines available at this time. Nor is there a means of developing and producing the volume of vaccine necessary to implement universal influenza vaccine recommendations given the inefficiency of current flu vaccine production.

In developing traditional vaccines, epidemiologists must predict months in advance which flu strains will be circulating during the next flu season in order to formulate a vaccine that targets the likeliest candidates. The selected strains are then manufactured in live, fertilized chicken eggs using a laborious process that takes 6 to 9 months.

Federally-funded alternative approaches that are now in development, such as cell-based production, wouldn't reduce the time necessary to produce vaccine and, furthermore, would require construction of large, committed manufacturing facilities.

The inefficiency of egg- or cell-based vaccine production makes it virtually impossible to respond to public health emergencies, such as the emergence of a pandemic avian flu, and impossible to reformulate vaccine if circulating strains do not match those in the vaccine, as was the case during the last flu season.

VaxInnate's Approach and M2e Flu Vaccine Candidate

VaxInnate M2e universal flu vaccine candidate represents a novel approach with respect to both vaccine design and production.

Unlike conventional flu vaccines, the M2e vaccine candidate targets the ectodomain of the M2 protein (M2e), an ion channel protein found on the surface of influenza A viruses. Because M2e is the most highly conserved surface protein of the virus, VaxInnate's vaccine candidate would eliminate the need for epidemiologists to identify and predict strain variants that emerge from year to year, and design an entirely new vaccine annually, as they must now.

Another key difference is the elimination of eggs or cells for vaccine production. VaxInnate's production technology is instead based upon the expression in recombinant bacteria of relevant influenza virus protein antigens fused to the bacterial protein flagellin. Flagellin interacts with the immune system's toll-like receptors (TLRs), which function in human immune cells as sentries to detect pathogens and mount a general immune defense. This initial defense, in turn, stimulates an adaptive immune response that includes production of pathogen-specific antibodies.

VaxInnate scientists believe that their technology can make it possible to produce flu vaccine of heretofore unseen quality rapidly and inexpensively in volumes sufficient to meet national and global needs in as little as a couple of months. No other vaccine technology in use or in development today has these same potential capabilities.

In addition, VaxInnate's use of bacterial expression for vaccine production doesn't require costly expansion of manufacturing capacity, as do other influenza vaccine products. Due to its efficiency and transferability, VaxInnate's flu vaccine could instead be produced in existing biotechnology facilities with microbial production capacity.

About VaxInnate

VaxInnate is a privately-held biotechnology company in Cranbury, NJ and New Haven, CT that is pioneering breakthrough technology for use in developing novel, proprietary vaccines for seasonal and pandemic influenza. This technology has the potential to dramatically improve the potency, manufacturing capacity and cost-effectiveness of influenza vaccines.

In addition to an hemagglutinin (HA)-flagellin flu vaccine candidate in clinical development at the University of Rochester, VaxInnate is on track both to begin a Phase II study of its M2e universal influenza vaccine candidate and to advance a vaccine candidate for H5 avian influenza virus - the most likely parent of a new pandemic strain -- into clinical development in 2009.

VaxInnate's technology platform is also being investigated for development of vaccines for other diseases. For more information about VaxInnate, please visit http://www.vaxinnate.com.