NIAID Announces Start of Human Trials for Universal Influenza Vaccine

Following years of research and development, NIAID scientists have begun enrolling participants in the first human trial of a universal flu vaccine candidate.

A phase 1 human clinical trial has begun on an experimental universal flu vaccine developed by scientists at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH).

The new announcement made by NIAID is the latest step toward an influenza vaccine capable of offering broad protection from flu viruses over multiple seasons. A study published in 2018 showed that a universal influenza vaccine candidate elicited strong antibody responses to the hemagglutinin (HA) stalk in mice, and more recently a team of investigators received a NIAID grant to continue developing a microneedle patch capable of delivering a universal flu vaccine candidate.

Current seasonal flu vaccines contain components selected to match circulating influenza viruses A and B and are designed to elicit a response to the head of the HA influenza protein, which is a constantly moving target due to antigenic drift. The new vaccine candidate—known as H1ssF_3928—represents a big step forward in years of research on developing a vaccine that targets a conserved region of the more constant stem of the protein.

In an interview with Contagion®, Barney Graham, MD, PhD, deputy director of NIAID’s Vaccine Research Center and chief of the Viral Pathogenesis Laboratory who has led the development of the vaccine, said his team has been working on this particular universal influenza vaccine concept for about 7 years. “The goal here is to overcome this great antigenic diversity that allows influenza to drift from season to season and then sometimes come in with pandemic strains,” he said of the potential for a vaccine creating immunity across multiple strains. “If we can see that happen in these people who are vaccinated that’s going to be very exciting.”

If successful, H1ssF_3928 has 4 benefits over currently available flu vaccines, says Graham. First, it does not require egg-based manufacturing; instead, it create antigens to target specific parts of the influenza virus. Next, it displays those antigens on nanoparticles to improve the way the immune system can see the antigen, and then elicits antibodies that are broadly reactive across multiple strains.

The candidate in this trial targets group 1 influenza viruses, including influenza A(H1N1), and Graham notes that the team hopes to begin a clinical trial on a vaccine candidate targeting group 2 influenza viruses, such as influenza A(H3N2), in about a year. In 2021 the team hopes to begin a trial on a vaccine candidate for influenza B viruses.

At least 53 healthy adults aged 18 to 70 years are expected to enroll in the trial. Of those, the first 5 participants will be aged 18 to 40 years and will receive a single 20-microgram intramuscular injection of the vaccine. The remainder of the 48 participants will receive 2 60-microgram doses of the vaccine, spaced 16 weeks apart. Investigators plan to stratify participants into 4 age groups to study how immune responses vary based on age, as well as prior exposure to the flu vaccine and flu infection, in 9 to 11 follow-up visits conducted over 12 to 15 months.

“We have identified antibody lineages, types of antibodies that have found ways of binding hemagglutinin that cut across multiple strains,” said Graham, noting that they’ve identified about a dozen such lineages that have the capacity to turn into broad-neutralizing antibodies, which they will be looking for in participant follow-ups. “The problem with doing this in adults is that they have been infected and immunized so many times, it may not be that easy to shift their overall pattern of responding to influenza.”

As such, there’s the possibility of a study of the vaccine candidate on younger children with limited exposure to flu. “Our hope is the way we’re presenting this, which is not the way you would typically see flu proteins in nature, we’re delivering it a way that hopefully the immune system can see it better and we’re hoping that we can shift the adult response toward these antibody lineages we’re interested in,” Graham said.