Human trial of mRNA universal flu vaccine begins

By Bronwyn Thompson

May 16, 2023

It’s still very early days, but the race to develop the first safe and effective mRNA-based influenza vaccine is gathering momentum.

The latest move sees a Phase 1 trial at Duke University in Durham, North Carolina, get under way, testing the safety and immune response of H1ssF-3928 mRNA-LNP, developed by the National Institute of Allergy and Infectious Diseases’ (NIAID) Vaccine Research Center (VRC).

Some 50 participants aged 18-49 will be split into three groups and given 10, 25 and 50 micrograms of the active drug, respectively. When optimal dosage is then determined, another 10 participants will get this measured jab. There will also be an additional group who will receive a current quadrivalent seasonal flu shot, so researchers have a comparative dataset that takes into account the immune response and safety of readily available influenza vaccines.

Those in the trial will then be regularly evaluated over 12 months to see how the drug’s immune response has fared and to assess its short-term and long-term safety.

While numbers vary depending on which seasonal influenza strains are prevalent, the Centers for Disease Control and Prevention estimates that, in its worse years from 2010 to 2020, the virus has resulted in up to 710,000 annual hospitalizations and 52,000 deaths in the US. Worldwide, the flu kills as many a 650,000 people each year.

“A universal influenza vaccine would be a major public health achievement and could eliminate the need for both annual development of seasonal influenza vaccines, as well as the need for patients to get a flu shot each year,” said Dr Hugh Auchincloss, acting NIAID Director. “Moreover, some strains of influenza virus have significant pandemic potential. A universal flu vaccine could serve as an important line of defense against the spread of a future flu pandemic.”

This trial comes after the initial NIAID’s Vaccine Research Center study on the safety and immune response of the H1ssF (H1 hemagglutinin stabilized stem ferritin) nanoparticle vaccine. The Phase 1 trial, from April 2019 to March 2020, delivered broad antibody responses in the 52 participants aged 18-70. The results of the trial were published last month in the journal Science Translational Medicine.

The H1ssF vaccine targets the flu protein hemagglutinin. One section of this protein – the 'head' – changes as the virus evolves into different strains, but the stem of the protein is much slower to be altered and remains fairly constant throughout influenza mutations. The researchers believe herein lies the key to a long-lasting, effective universal preventative vaccine.

The new trial combines the H1ssF nanoparticle vaccine with messenger RNA (mRNA) as the platform, with the end goal that it'll deliver a more efficient, targeted immune response.

"During the course of a flu season, the influenza virus drifts, undergoing small, but significant changes that make current vaccines less effective," said Dr Emmanuel Walter, chief medical officer and director of the Duke Vaccine and Trials Unit. "We are hopeful that this vaccine could offer protection across those sorts of change."

The H1ssF-3928 mRNA-LNP vaccine is not the only potential flu shot at this stage of development. CureVac and GSK have begun a combined Phase 1/2 trial for their multivalent, modified mRNA seasonal influenza vaccine. Pfizer and BioNTech launched Phase 3 of their quadrivalent nucleoside-modified messenger RNA (modRNA) vaccine last September, administering the drug to 25,000 adults in the US aged 18 and over. Theirs is yet another approach, targeting four known flu strains recommended by the World Health Organization (WHO). They've also begun Phase 1 trials of a flu shot combined with their COVID-19 Omicron BA.4/BA.5 vaccine.

However, last month, Moderna admitted its Phase 3 trial of its vaccine, mRNA-1010, “did not accrue sufficient cases at the interim efficacy analysis to declare early success.” This follows on from 2021's disappointing trial results.

Source: National Institute of Allergy and Infectious Diseases