Nov 2, 2018

Novel antibody study could lead to near-universal flu protection

Illustration: Rebecca Zisser/Axios

A team of scientists took a novel approach to the problem of protecting people against both A and B types of flu viruses. They used llama antibodies to create a nasal spray that would block the viruses before they can take hold in the body, according to a preclinical mouse study published in Science Thursday.

Why it matters: This approach could bring us closer to developing a universal flu vaccine before the next influenza pandemic hits — which, if we're not prepared, would likely kill tens of millions globally. While this study is not on a vaccine per se, it aims to provide similar "near universal" protection against multiple influenza viruses.

What they did: The team immunized llamas with 3 different influenza viruses plus viral surface proteins, called hemagglutinin, from 2 other flu strains.

  • llamas were chosen because their antibodies have unique properties beneficial for drug development, like their small size and ability to bind to multiple targeted epitopes.
  • They then harvested 4 antibodies that neutralized many flu strains (both A and B) from the llamas.
  • They linked parts of the antibodies into a single molecule that was spliced into a neutralized virus that's sometimes used in gene therapy to disseminate the material.

What they found: In lab cultures, the antibody serum protected against 60 different flu strains. When given to mice, either via an intranasal spray or direct infusion, the mice showed "significantly higher survival rates" than untreated rodents.

"The multi-domain antibodies were able to neutralize all 60 human and avian influenza viruses that were tested except for one H12 virus. Influenza H12 viruses are avian influenza viruses, which so far have not been transmitted to humans."
— Study authors Joost Kolkman of Janssen Infectious Diseases and Ian Wilson of Scripps Research

Between the lines: William Schaffner, an infectious disease specialist at Vanderbilt University, points out that if further testing doesn't alter the serum or distribution, the serum would differ from a vaccine in that the antibodies would directly enter humans' nasal mucus membranes, "so that [the flu virus] never gets a foothold and therefore gives more protection."

  • Vaccines, on the other hand, are typically injected and will prompt the human body to build its own antibodies against the viruses.
  • Its potential to be distributed via a nasal spray that anyone could administer could be important during an emergency, Schaffner says.
  • One of the potential safety concerns is the use of the viral vector, which has been used in some gene therapies but needs further study, according to University of Chicago professor Carole Henry Dunand. "There are still some limitations to [virus vector] use in humans and it might take [a while] for such a therapy to be available to the public compared to more classical vaccine FDA-approved strategies."

What they're saying: Multiple experts tell Axios this is an exciting new approach that could eventually lead to the development of the "holy grail," which is an immunization against a broad spectrum of flu viruses to combat a future pandemic.

"This line of investigation is outside of the box because what they are creating is a multi-domain antibody, not creating a new vaccine... It's a novel way to create near universal influenza protection."
— William Schaffner
"This is a great start — I call it the iphone version 1.0. ... We've got a long way to go before a universal flu vaccine. But, at the same time, we've made more progress over the last 24 months than we have over the last 10 years."
— Michael Osterholm, director, University of Minnesota’s Center for Infectious Diseases Research and Policy

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