H5N1 is a highly pathogenic influenza virus which has the potential to create a deadly pandemic. It has been closely monitored and has created great concern among many governments and world health organizations. According to the CDC, the highly pathogenic strain of avian influenza, known as H5N1, has caused millions of domestic poultry deaths in Asia over the past several years. There is a growing concern that the H5N1 virus will become capable of efficient and sustained transmission among humans, which has the potential to cause an influenza pandemic with high rates of illness and death worldwide. New research suggests that currently circulating strains of H5N1 are, in fact, changing with respect to their host interactions in animals. For example, one study found that ducks infected with H5N1 virus are now shedding more virus for longer periods even without symptoms of illness.
Human H5N1 Cases
The World Health Organization has reported human cases of avian influenza A (H5N1) in Asia, Africa, the Pacific, Europe and the Near East. Indonesia and Vietnam have reported the highest number of H5N1 cases to date. Overall mortality in reported H5N1 cases is approximately 60 percent. The majority of cases have occurred among children and adults less than 40 years old, and mortality was highest in cases aged 10-19 years old. Studies have documented the most significant risk factors for human H5N1 infection to be direct contact with sick or dead poultry or wild birds, or visiting a live poultry market. Although laboratory studies have suggested that most H5N1 strains are susceptible to influenza anti-viral drugs, most human H5N1 cases have been hospitalized late in their illness with severe respiratory disease, when drugs would be less effective. To date, there have been more than 500 confirmed cases of H5N1 worldwide.
Our Vaccine Candidate
PXVX0103 is an oral, live adenoviral-based vaccine against avian influenza (H5N1) or “bird flu.” This vaccine (Ad4-H5-Vtn administered as oral capsules) was evaluated in an (over 160 subjects) ascending dosage Phase I placebo-controlled clinical trial. The Ad4-H5-Vtn vaccine replicated in the GI tract of the volunteers. The Ad4-H5-Vtn vaccine induced a cellular immune response to the H5 HA. Additionally, when the volunteers received a subsequent single intramuscular boost with H5 HA protein, they had high rates of antibody response, with HAI seroprotection levels of up to 89%. In addition to demonstrating proof of concept for an oral pre-pandemic vaccine, the H5N1 data demonstrates the ability of an Ad4 vector based vaccine in combination with another mode of vaccine delivery has the potential to generate a more robust antibody responses than traditional vaccine methodologies.
Reactogenicity symptoms from the Phase I trial were found not to be related to dose level. Abdominal pain, nausea/vomiting and nasal congestion were more frequent in vaccinees compared to placebo, but were generally mild.
This oral priming, parenteral boosting regimen (“heterologous prime-boost”) of the Ad4-H5-Vtn vaccine will be further explored in Phase II studies.
The results of the Phase I study were published in the journal The Lancet Infectious Diseases, and the publication is available online and can be accessed here: Safety and Immunogenicity of an Oral, Replicating Serotype 4 Vector Vaccine for H5N1 Influenza. The full protocol for the Phase I study is available for download here: Clinical Research Protocol.