WASHINGTON – The National Institutes of Health announced two new clinical trials are enrolling volunteers to test an experimental vaccine against the H7N9 avian influenza virus.

The studies are sponsored by the NIH’s National Institute of Allergy and Infectious Diseases (NIAID) and will test different dosages of the inactive vaccine candidate, called 2017 H7N9 IIV, along with different vaccination schedules.

“As we experience one of the worst seasonal influenza epidemics in recent years here in the United States, we also must maintain a scientific focus on novel influenza viruses, such as H7N9, that have the potential to cause a pandemic,” said NIAID Director Anthony S. Fauci, M.D. “These new clinical trials will build upon initial studies of earlier versions of an H7N9 vaccine candidate to provide a more detailed picture of its safety and ability to generate a protective immune response to current H7N9 strains.”

The two clinical trials will test the experimental 2017 H7N9 inactivated influenza vaccine developed by Lyon, France-based Sanofi Pasteur and supported by the Biomedical Advanced Research and Development Authority (BARDA), a component of the US Dept. of Health and Human Services Office of the Assistant Secretary for Preparedness and Response. The new version of the vaccine candidate uses an inactivated form of H7N9 influenza virus collected in 2017, which NIH said will increase the likelihood that the vaccine will provide immunity against a newly evolved strain of H7N9, which is currently circulating in the wild.

Some participants will receive an adjuvant — which helps create a stronger immune response — called AS03, along with the test vaccine, to confirm that the adjuvant can boost the immune response to the vaccine., as previously shown for other influenza viruses of pandemic potential. The vaccines business of GSK in Wavre, Belgium, created the adjuvant with support from BARDA.

Principal investigator Lisa A. Jackson, M.D., of the Kaiser Permanente Washington Health Research Institute in Seattle, will lead one clinical trial which will test the vaccine candidate at different dosages, both with and without the AS03 adjuvant. As many as 420 male and non-pregnant female volunteers ages 19 to 64 years and up to 300 volunteers older than 65 years of age are needed for this trial.

The second clinical trial, led by Kathleen M. Neuzil, M.D. of the Univ. of Maryland School of Medicine, will test the H7N9 vaccine candidate with AS03 adjuvant in conjunction with a quadrivalent seasonal influenza vaccine which is designed to protect against for different flu viruses. NIH explained that investigators will be able to learn whether the H7N9 vaccine candidate affects the immune response to the seasonal influenza vaccine, and vice versa, by administering the vaccine candidate to some volunteers who have received the seasonal influenza vaccine and some who have not. The H7N9 vaccine candidate will be given to 150 healthy volunteers ages 19 to 64 years, NIH said.

Public health authorities say the H7N9 avian flu may be the most lethal bird flu virus to emerge to date. Symptoms of infection can include high fever (greater than or equal to 100? or 38°C) and cough and difficulty breathing. Patients with severe illness can exhibit severe pneumonia, hypoxemic respiratory failure, multi-organ dysfunction, septic shock and secondary bacterial and fungal infections, according to the World Health Organization (WHO).

The virus seems to spread through poultry flocks causing no visible signs of illness in the birds, therefore anyone handling live poultry may not be aware that birds are infected. In 2013, the H7N9 virus was first reported in humans in China. A single case of H7N9 in China was reported in February.

NIH said the virus currently does not spread easily from person to person. People typically become infected through direct exposure to infected poultry or contaminated environments. There is a concern that if the virus mutates and becomes easily transmissible between humans, it could result in an influenza pandemic because most people have little to no immunity to it. NIH said H7N9 has a high mortality rate, resulting in death in 39 percent of those who became infected.

In June 2017, an international team of scientists at The Scripps Research Institute in La Jolla, California, examined mutations that could occur in the H7N9 genome. The team focused on the H7 hemagglutanin, which is a protein found on the surface of flu viruses that enables them to latch onto host cells. H7N9 has specific receptors on bird cells, but not receptors on human cells.

In lab experiments, mutant H7 hemagglutanin successfully latched onto cells in samples of human trachea tissue.

“We suggest that understanding mutations that can confer human-type receptor binding will benefit risk assessment in worldwide surveillance of H7N9 in poultry and humans,” the researchers reported in the journal PLOS Pathogens.