Viruses causing influenza and COVID-19 continually evolve to escape our vaccine protections. The French firm Osivax is developing vaccines that are harder for the viruses to evade.
Many life-saving vaccines have been developed and approved to protect against viral infections including COVID-19 and influenza. Commercially available vaccines typically activate the production of antibodies against fragments called antigens on the surface of viruses, such as the spike protein in the case of the coronavirus responsible for COVID-19.
However, influenza and coronaviruses are able to evolve their surface antigens, making it harder for antibodies to combat the invaders. This means Covid booster vaccines are often needed to target new strains of the pathogens. And in the case of seasonal influenza, vaccine manufacturers must predict which strain will be present, which can provide insufficient protection to vulnerable populations.
To get around this issue, Osivax is developing vaccines that activate T cells instead of antibodies against viral antigens. Unlike antibodies, T cells can spot antigens hidden inside viruses, and many of these hidden antigens don’t evolve very often.
According to Delphine Guyon-Gellin, chief business development officer at Osivax, antibodies are much easier to target with a vaccine than are T cells. This is because antibodies can be measured with a simple blood test, whereas T cells must often be tested in tissue samples.
“If you can get an antibody-based vaccine that protects well and neutralizes the virus, you wouldn’t need to care that much about T cells,” said Guyon-Gellin. However, she added that antibody-based vaccines are usually limited against highly mutating viral infections like influenza and COVID-19.
Osivax makes recombinant protein vaccines that self-assemble into virus-like-particles (VLPs). These VLPs are designed to resemble viruses enough to trigger the immune system to attack them, and can activate both antibodies and T cells. By targeting antigens inside of the viruses, Osivax’s VLP vaccines could provide future-proof vaccines for viral infections.
Osivax’s lead program is in phase 2 testing for the prevention of influenza. So far, the vaccine has shown around 75% protection against two strains of influenza in clinical trials.
“The average efficacy of flu vaccines over the last 10 years has been 40% in adults. In the elderly, it’s been closer to 30%,” commented Guyon-Gellin. “What we’ve observed in our clinical trial is twice that.”
If a future-proof influenza vaccine enters the market, it could lower the danger of influenza in the elderly population, which is one of the most vulnerable groups to the infection. It could also serve as a stock vaccine in future pandemics.
“As we saw with COVID-19, you identify the virus and then you need a bit of time to produce a fully tailored vaccine and supply it,” said Guyon-Gellin. The stock vaccine could help fill vaccine needs until more specific vaccines arrive.
To fund its vaccine development, Osivax is raising a Series B investment round, and its next clinical milestone is a phase 2b trial of its lead influenza candidate beginning in 2023. Osivax is also supported by a €10 million grant from Bpifrance, which it received in June 2022.
In addition to influenza and Covid, Osivax has candidate vaccines in development against latent viral infections such as human papillomavirus (HPV). The firm is also exploring the potential for deploying the technology to treat cancer.
A number of VLP-based vaccines are already in broad use for the prevention of infections such as hepatitis B, HPV and malaria. Osivax chose VLPs as they have some advantages over viral vector vaccines and messenger RNA (mRNA) vaccines. For example, some viral vector vaccines aren’t well suited to repeated immunization, and mRNA vaccines tend to have a lower tolerability and duration than protein vaccines.
One standout example of the effectiveness of vaccines targeting T cells is the shingles vaccine Shingrix. This indicates that the strategy has potential in spite of how complex the development can be.
“The best benchmark of leveraging a T-cell vaccine could be Shingrix,” said Guyon-Gellin. “But clearly it’s a new field that has been less investigated.”
There are many companies that are seeking universal, future-proof vaccines for influenza and COVID-19 that target T cells. Some examples include Emergex Vaccines and ConserV Bioscience.
However, other efforts have been unsuccessful in targeting influenza with T-cell vaccines. In 2020, Vaccitech abandoned its flu vaccine program after its candidate failed to reach the goals of a phase 2 trial. In Israel, an influenza vaccine developed by the company BiondVax failed to prevent influenza in a phase 3 trial.
Guyon-Gellin is confident that Osivax can succeed where others have failed as its vaccine has shown robust clinical efficacy in independent trials so far.
The COVID-19 pandemic has increased interest in vaccine technology, with mRNA therapeutics reaching the mainstream as a result. While private investments remain limited for vaccine developers in influenza, Guyon-Gellin observed that public investors and governments are more prepared to bankroll the development of better vaccines for influenza.
“During the Covid pandemic, a lot of public funding for influenza was put on hold to devote more resources to the Covid emergency,” said Guyon-Gellin. “Now, we are seeing those sectors getting back into public funding.”