Study points to route for ‘one and done’ flu vaccine – pharmaphorum

Scientists in the US have developed a new universal form of influenza vaccine that they say could protect against all strains of the virus and do away with the annual scramble to match shots to circulating flu strains.

The team led by researchers at Oregon Health & Science University (OHSU) think their 'one and done' model which uses a cytomegalovirus (CMV) vector could confer lifetime immunity against the evolving virus.

While still in the animal testing stage, initial results published in Nature Communications have been promising against H5N1, a bird flu strain that is a frontrunner to cause a new pandemic.

In the past few years, a highly pathogenic strain of H5N1 has emerged that can jump between 50 animal species, raising the threat level, and leading the World Health Organization to suggest that the next pandemic is most likely to be caused by an influenza virus.

The OHSU team have demonstrated in non-human primates that their CyCMV/Flu candidates were able to protect animals from H5N1 even though the vaccines were based on a historic H1N1 strain of the virus that was responsible for the 1918 Spanish flu outbreak that killed millions of people worldwide.

In the study, six of 11 macaque monkeys inoculated with CyCMV/Flu survived after exposure to H5N1, which has a very high fatality rate. In contrast, a control group of six unvaccinated primates exposed to the H5N1 virus all died.

Jonah Sacha, head of pathobiology at the university's National Primate Research Center and one of the leaders of the programme, has suggested that it could be possible to develop the technology into a usable flu vaccine within the next five years.

That is partly because OHSU's CMV platform has already transitioned from the lab to clinical testing. The technology underpins a preventive HIV vaccine candidate developed by Vir Biotechnology, VIR-1388, that recently started phase 1 testing in the US and South Africa.

OHSU's method involves inserting small pieces of target pathogens into a weakened form of CMV, a virus that infects most people in their lifetimes and produces mild or no symptoms unless they are immunocompromised.

The virus acts as a vector specifically designed to induce an immune response from the body's T-cells, focusing on nucleoproteins found in the interior of the flu virus ( M1, NP, and PB1) that are less likely to mutate and evolve over time.

This approach differs from existing flu vaccines, which are designed to induce an antibody response that targets strains based on the arrangement of hemagglutinin (HA) and neuraminidase (NA) glycoproteins covering the exterior surface.

"It worked because the interior protein of the virus was so well preserved," said Sacha. "So much so that, even after almost 100 years of evolution, the virus can't change those critically important parts of itself."

And, according to the researchers, the same approach could be used for other pandemic viruses, including COVID-19.

"It's a very viable approach," said Sacha. "For viruses of pandemic potential, it's critical to have something like this. We set out to test influenza, but we don't know what's going to come next."

Other groups are also working on ways to deliver a universal flu vaccine.

One team at the National Institutes of Health (NIH) in the US is running a phase 1 trial of a 'mosaic' vaccine, based on a virus-like particle (VLP) that displays HA antigens in repeating patterns on self-assembling nanoparticle scaffolds. Another is testing an mRNA-based vaccine coding for the tail portion of the HA antigen, which is more conserved between strains.

Read more:

Study points to route for 'one and done' flu vaccine - pharmaphorum