August 8, 2019

An early-stage clinical trial is evaluating two licensed seasonal influenza vaccines, administered with or without novel adjuvants, for their safety and ability to generate an immune response. Adjuvants are compounds added to vaccines to induce stronger and longer-lasting immune responses. The Phase 1 study is enrolling healthy adult volunteers at eight sites across the United States. The trial is funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

According to the Centers for Disease Control and Prevention, influenza vaccination can greatly reduce the risk of infection or severe influenza-related illness that may require hospitalization. Although seasonal influenza vaccines have been widely available for decades, their effectiveness varies from year to year, depending on how well the vaccine matches the disease-causing influenza virus strains that are circulating at that time. When a person receives a vaccine containing an adjuvant, they are more likely to produce a stronger immune response to the vaccine, which may better protect them from the disease.

“As part of a comprehensive research effort to develop more effective and durable influenza vaccines, NIAID not only supports the development of new vaccines, but also efforts to improve seasonal vaccines that are already available,” said NIAID Director Anthony S. Fauci, M.D. “We hope this trial will increase our understanding of how adjuvants could help confer better protection from seasonal influenza.”

The trial will enroll 240 healthy volunteers ages 18 to 45 years at eight Vaccine and Treatment Evaluation Units (VTEUs)—a network of clinical trial sites funded by NIAID. Patricia Winokur, M.D., from the University of Iowa Carver College of Medicine in Iowa City, is principal investigator of the trial, which is expected to last approximately 18 months.

Volunteers will be randomly assigned to receive one dose of either the Fluzone® Quadrivalent Influenza Vaccine or Flublok® Quadrivalent Influenza Vaccine. The vaccine will be given alone or in combination with either the AF03 or the Advax-CpG55.2™ adjuvant. Fluzone and Flublok are manufactured by Sanofi Pasteur, the vaccines global business unit of Sanofi, and are reformulated each year to best match the anticipated seasonal influenza strains selected by the World Health Organization. Participants will receive the northern hemisphere 2018-2019 influenza season formulations of Fluzone and Flublok at the start of the trial. Fluzone is made from inactivated influenza viruses grown in chicken eggs. Flublok is an egg-free recombinant vaccine comprised of a surface protein of influenza virus, hemagglutinin, specifically engineered to achieve an exact genetic match to the WHO-selected influenza strains each year. The Flublok proteins are manufactured in insect cells using a genetically engineered baculovirus. 

The two novel adjuvants being tested have shown promise in animal models at enhancing the immune response to influenza vaccines. In additional animal studies, both were shown to be well-tolerated when given in conjunction with either Flublok or Fluzone. One of the adjuvants, AF03, developed by Sanofi Pasteur, has also been shown to substantially improve humans’ immune responses to avian influenza vaccines(link is external). The other adjuvant, Advax-CpG55.2™, developed by Vaxine Pty Ltd based in Adelaide, Australia, is the most recent formulation of a sugar-based adjuvant that has been shown to increase the immune response elicited by vaccines for influenza in humans. NIAID supported the development of the Advax-CpG55.2™ combination through its Adjuvant Discovery and Development Program.

After receiving the one of the vaccines with or without one of the adjuvants, participants will be monitored and return for regular clinical visits for at least 57 days. This will allow researchers to monitor volunteers for adverse effects and take blood samples that will help the researchers track the immune responses to the vaccine.

Ninety days after receiving the first vaccination, all volunteers will receive a dose of a 2019-2020 seasonal quadrivalent influenza vaccine without adjuvant and will be observed for adverse effects. Volunteers who received Fluzone earlier in the study will receive the current Fluzone vaccine, and volunteers who received Flublok will receive the current Flublok vaccine. The participants’ final clinical visit, which will take place roughly a year after their first vaccination, will involve a blood draw and a total accounting of any adverse effects.

When completed, the study will provide important safety and immunogenicity data on adjuvated seasonal influenza vaccines. This information may help determine the best combination of vaccine and adjuvant needed to provide robust immunity, and ultimately improve the protection afforded by seasonal influenza vaccination.

For more information about this trial, please visit ClinicalTrials.gov, and search the identifier NCT03945825.

NIAID conducts and supports research — at NIH, throughout the United States, and worldwide — to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID website.

A person receives the seasonal influenza vaccine (flu shot).NIAID