Intranasal Influenza Vaccine
Influenza Vaccine is unique in that it behaves like a drug product in terms of sales growth. Re-vaccination is required yearly against the current strains of influenza. Increased awareness of the benefits of influenza vaccine, favorable public policy recommendations, and improvements in vaccine delivery are causing market growth. Vaxin’s most advanced product candidate, a non-replicating adenovirus-vectored nasal influenza vaccine, has completed an initial Phase I clinical trial using a monovalent formulation. This study demonstrated safety and serological response when a recombinant adenovirus vector was used to deliver the influenza hemagglutinin (HA) gene by nasal administration (The influenza HA protein is the most important protective antigen in influenza vaccines; it is responsible for attaching the virus to the host cell during infection). Cells transduced by adenovirus vectors, principally in the nasal mucosa, express the HA protein which stimulates an immune response. The immune response has been shown to include systemic antibodies, and is also expected to include local, mucosal antibodies.

Clinical dose escalation studies are planned for 2006 using monovalent and for 2007 using trivalent intranasal formulations of multiple influenza strains, followed by a phase II trivalent study. In addition, the National Institutes of Health (NIH) recently awarded Vaxin a $3 million Challenge grant in support of development of a non-replicating adenovirus-vectored nasal vaccine against a highly pathogenic avian influenza virus (H5N1) in preclinical animal studies. Human clinical trials for this H5N1 influenza vaccine are expected to begin in 2007.

Vaxin’s influenza and avian influenza vaccines have the following advantages over products currently on the market or in development:

• Nasal delivery of a non-replicating vaccine without the concerns inherent in a replicating virus vaccine (e.g., FluMist) such as pathogenicity, reassortment, shedding and transmission.

• Likelihood of being indicated for a broader population including 50-64 year olds, the elderly (over 65 years old), and children including the very young (under 5 years old) due to the excellent safety profile of adenovirus-vectored nasal vaccines.

• More cost effective manufacturing: Vaxin’s product will be manufactured in cell culture. All currently marketed influenza vaccines (live or killed virus) require embryonated chicken eggs as a substrate for production. Inherent in the egg process are supply risks (e.g., avian flu outbreaks; limited supply of qualified eggs), low yield, and difficulty in manufacturing process control.

• More rapid response to changing influenza strains. Replacing the egg-based process with the PER.C6 cell culture manufacturing process will give Vaxin a start-up time advantage when an unexpected flu strain emerges after other manufacturers have exhausted their seasonal egg supply.

• Since Vaxin does not use eggs, there would not be a contraindication for contamination by chicken pathogens and allergic reactions to egg proteins.

Intranasal and Epicutaneous Anthrax Vaccines
Vaxin’s anthrax vaccine program also uses the adenovirus technology and addresses shortcomings inherent in both the approved anthrax vaccine, as well as other anthrax vaccines currently in development. The vaccine will contain the protective antigen (PA) which is a main component of the injectable anthrax vaccines. Vaxin’s program provides a simple intranasal delivery which eliminates the need for difficult logistics related to needle injections for mass immunization. Vaxin’s anthrax vaccine is currently in pre-clinical testing; intranasal application has shown immunogenicity and protection in laboratory animals. Initial human clinical trials could start as early as 2008.

In addition, Vaxin scientists have identified new proteins that may play vital roles during germination and early outgrowth of anthrax spores. These novel anthrax antigens may boost the overall vaccine profile by eliciting an immune response that arrests spore germination at the onset of the pathogen’s life cycle. The one licensed anthrax vaccine and many other experimental products principally target the PA protein expressed from a plasmid in Bacillus anthracis. Vaxin’s germination-targeted anthrax vaccine may appear as a useful adjunct to the PA-based vaccine. More importantly, elicitation of an immune response against germinating anthrax spores may be crucial in conferring protection against bioengineered anthrax spores whose PA is replaced by exogenous toxins. Overall, this two-pronged approach to protection, in addition to the needle-free administration, helps make Vaxin’s anthrax vaccine meet or exceed the government’s requirements for an improved anthrax vaccine. The NIH recently awarded Vaxin a $2.4 million Challenge grant in support of development of a non-replicating adenovirus-vectored nasal vaccine against PA and germination-associated anthrax antigens.

An epicutaneous anthrax vaccine is also under development. Vaxin Scientists have demonstrated that non-replicating E. coli (K12 or B laboratory strains) vectors overproducing pathogen-derived antigens (e.g., PA), when delivered to the outer layer of skin by a patch, can by disrupted by an innate defense mechanism followed by cutaneous extraction of intravector antigens and elicitation of a systemic immune response against the pathogen. This mode of vaccination may emerge as the most cost-effective means to promote vaccine coverage during an emergency.

In Ovo Avian Influenza Vaccines.
Economic loss caused by avian influenza has been a major problem in poultry industry. Moreover, a highly pathogenic H5N1 avian influenza virus has ravaged poultry in multiple countries during recent years. Evidence of bird-to-human and subsequent human-to-human transmissions and its lethality in humans are emerging. Resurgence of the virus and its variants despite the killing of enormous numbers of healthy birds to create a buffer zone in Hong Kong in 1997 suggests that there may be no possibility of eradicating this fatal disease. Sporadic human infection with avian influenza viruses is raising concerns that reassortment between human and avian subtypes could generate viruses of pandemic potential. Vaccination en masse of at-risk poultry to prevent wide dissemination of avian influenza virus appears to be a humane, effective, and economical approach in protecting domestic birds as well as averting a global pandemic. Vaxin Scientists and their associates have demonstrated the potency of a non-replicating adenovirus-vectored in ovo vaccine against avian influenza. Vaxin’s avian influenza vaccines can be easily generated, manufactured, and stored. Most notably, propagation of the pathogen is not required for generating vectored vaccines because the relevant influenza antigen genes can be synthesized or amplified directly from field samples. This is particularly important for production of H5N1 vaccines because this strain is too dangerous and difficult to propagate. In addition to the above criteria, commercial concerns factor heavily in the poultry industry. In ovo administration of vaccines using a robotic injector saves labor and expedites the process during mass vaccinations. Adenovirus-vectored vaccines are also capable of differentiating vaccinated-but-uninfected animals from their infected counterparts because markers of the pathogen that are not encoded by the vector can be used to discriminate the two events. The NIH recently awarded Vaxin a $1,000,000 SBIR Phase II grant in support of development of a non-replicating adenovirus-vectored in ovo vaccine for mass immunization of poultry against avian influenza.

Other research programs.
Other research programs include nasal and epicutaneous vaccines against tetanus and Alzheimer disease for humans.