Preventing flu with an antibody-plus-Tamiflu universal vaccine

The problem with the influenza virus is it can rapidly mutate into strains that are resistant to the yearly vaccine. That has made the search for a universal vaccine all the more challenging.

Researchers at the National Institutes of Health’s National Institute of Allergy and Infectious Diseases (NIAID) have found a new clue to providing broad-based protection against the flu—and it rests partly on Roche’s FDA-approved remedy Tamiflu.

Using mouse models of flu, the NIAID team tested an antibody that recognizes a protein called hemagglutinin, which sits on the surface of the virus and helps it spread to healthy cells. Current flu vaccines work by recognizing the head of hemagglutinin and blocking its ability to shuttle the virus into cells. Problem is, that’s the region that can rapidly mutate to escape the vaccine. So the researchers used an antibody that targets the stem domain of the protein instead—a region that’s far more resistant to mutations.

When they combined the antibody with Tamiflu, which works by inhibiting another flu surface protein called neuraminidase, the mice were better able to survive a severe viral infection. The researchers reported their discovery in the Journal of Experimental Medicine.

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Although anti-stem antibodies that target hemagglutinin have long been considered a promising approach in the development of next-generation flu vaccines, the NIAID researchers wanted to gain a better understanding of their mechanism of action. As they conducted research in flu cells, they discovered that the antibodies not only work against hemagglutinin but also inhibit neuraminidase. That’s important, because neuraminidase normally promotes the replication of the flu virus.

Hence, the inspiration to add Tamiflu to the mix. Adding the drug to the anti-stem antibody they tested in mice boosted the activation of immune cells that were exposed to the flu, they reported.

"The ability of neuraminidase inhibitors to enhance … immune cell activation [by anti-stem antibodies] bound to viruses or infected cells suggests the possible clinical synergy,” the authors wrote.

There are a handful of universal flu vaccines in late-stage human testing, including hVIVO’s FLU-v. Earlier this month, the company’s shares surged on news that its vaccine reduced symptoms and stimulated an immune response in a phase 2b trial. FLU-v is a “synthetic polypeptide” vaccine that’s designed to provide protection against multiple strains, including emerging mutations of the virus. The company is now preparing to bring the vaccine into phase 3 testing.

Several other approaches to universal flu protection have shown promise in preclinical studies. In November, for example, scientists led by Scripps Research Institute and Johnson & Johnson’s Janssen reported that they developed a new type of antibody from llamas immunized with a flu vaccine. The molecules, called neutralizing single-domain antibodies, were able to protect mice against most strains of influenza A and B, they reported.

Although the current flu vaccine has so far proven more effective than last year’s version, the threat from the virus is still evident. Of the 54 jurisdictions that report flu activity to the Centers for Disease Control and Prevention, 48 said the infection was widespread last week.