One Flu Vaccine May Soon Just Be Enough

Florian Krammer at Mount Sinai has developed a universal flu vaccine that can grant immunity against all strains of influenza and eliminate the need for revaccination. It was recently tested in the phase one trial and the results were promising, suggesting that the use of chimeric HA to target the stalk of the HA glycoprotein is able to effectively produce antibodies against a wide variety of influenza strains.

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By Rachel Chuong

Let’s face it, you probably dread receiving the flu shot. The long wait, the painful needle, and the subpar band-aid combine to create a truly unpleasant experience. Worst of all, you need to redo it every year.

Unlike other diseases that are preventable with a single vaccination, an annual seasonal flu vaccine is the only option available to the public to combat influenza due to the virus’s ability to quickly evolve. However, in a study conducted at Wuhan’s Tongji Hospital to investigate the correlation between getting the flu and getting COVID-19, scientists discovered that 11.8 percent of patients who contract COVID-19 also contract influenza co-infections. The effects of these co-infections were far more catastrophic for the patient, including an increased risk factor of prolonged hospital stay. Thus, battling the flu season has become more crucial than ever before and scientists fear that the current flu vaccine, with its inadequacy to trigger immune responses against virus strains besides its designated target, may no longer be adequate.

The vaccine’s limitations are due to its contents, which include three or four specific strains of the weakened virus in addition to haemagglutinin (HA) proteins. HA, an antigenic glycoprotein, triggers the production of antibodies in an immune response and is found on the surface of the influenza virus. The HA protein comprises two structures: the head and stalk. The current vaccine triggers an immune response, producing antibodies that neutralize the “head” of the HA protein on the virus’s surface. Notably, the head is variable between different strains of the virus and is able to mutate and evolve rapidly. As a result, healthcare personnel must reformulate and readminister the flu shot annually.

For years, scientists have been attempting to create a universal flu vaccine, a single vaccination that would grant lifelong immunity against all the strains of influenza. Though this goal has long been labeled an unattainable fantasy, the promising results from a recent trial suggest that the aspiration may soon become a reality.

A team led by Dr. Florian Krammer, professor of microbiology at the Icahn School of Medicine at Mount Sinai, hypothesized that shifting the vaccine from the variable head to the uniform stalk could yield promising results. The team found that the stalk domain is well conserved between different strains, as it possesses neutralizing B-cell epitopes, the portion of the antigen that triggers the immune response, and these epitopes are constant among the various viral strains. The obvious solution, therefore, would be to produce a vaccine that triggers an immune response to the stalk domain. But doing so is not that easy.

Targeting the stem structure is challenging. Immune memory cells in our bodies are habituated to producing antibodies that target the HA’s head, because the shape of the antibodies specifically matches with that of the head portion. To produce antibodies that match with the stalk, researchers sought to use only the HA stalk in the vaccine. But they realized that this was impossible, as the stalk on its own is immensely unstable. To circumvent this issue, Krammer and his colleagues developed synthetic chimeric HAs, or artificial head and stalk combinations, allowing the team to use stabilized stalk portions.

Ultimately, Krammer found that using the chimeric HAs in the vaccine effectively produced antibodies against the stalk. Thus, the response against the stalk was able to dominate over the response against the head because the antibodies produced were specifically tailored for the stalk. Furthermore, because the vaccine targets the conserved stalk domain, it is able to effectively prevent infection from many different strains. Theoretically, this ability would eliminate the need for revaccination in one’s lifetime as it would result in absolute immunity against most emerging strains of influenza. In addition, the vaccination could be a groundbreaking preventive measure against existing strains of influenza, thus preventing future influenza pandemics and eliminating the hassle and expenses associated with revaccination.

Krammer and his team conducted a Phase 1 clinical trial, a test of a drug’s safety and ability to trigger an immune response, on their vaccine. The trial had two groups: 51 participants who received the vaccine and 15 participants who received placebos. The results concluded that a single vaccination produced antibodies against the stalk domain. Still, this trial did not test protection against influenza, as the humans were not subjected to the virus itself. Notwithstanding, in a follow-up test, the human antibodies created during the trial were transferred to mice which were then exposed to the virus. The treated mice lost insubstantial weight and did not contract the flu, suggesting that the antibodies were effective because weight loss is a symptom of influenza infection.

As promising as the results are, the vaccine awaits a long process before being approved and available to the public. While the “first step” is completed, Krammer aspires to develop additional chimeric HAs that would render the vaccine truly universal, a process that will require at least two years to accomplish. In addition, once the vaccine is complete, it awaits Phase 2 trials to further evaluate its safety, and Phase 3 trials, which compare it to existing treatments to determine effectiveness. The results of these future trials will decide whether the vaccine is approved by the FDA and ultimately, whether it can be available to the public. As revolutionary as this creation is, the project’s primary impediment is its lack of funding due to a lack of interest in the matter. Krammer surmises that the lengthy development procedure and slow progress cause a lack of interest and funding from pharmaceutical companies. Nonetheless, as the universal flu vaccine continues to advance, its successes will be recognized and the project will gain more momentum. Today, we are closer than ever to achieving the universal flu vaccine, and soon enough, just one flu vaccine will be enough.