The FINANCIAL -- In a landmark discovery, researchers from
Crucell Holland B.V. and The Scripps Research Institute, today announced
the identification of the first human monoclonal antibodies that appear
capable of disabling all influenza B viruses.
The discovery, published today in the journalScience, addresses a significant missing link in development of universal therapies and a vaccine. The research was conducted by a team of scientists at Crucell, part of the Janssen Pharmaceutical Companies and Scripps Research, along with collaborators from the Centre of Influenza Research at the University of Hong Kong.
“Despite current vaccines and treatments, influenza remains a major medical problem worldwide. There is a strong need for development of new therapies that go beyond treatment or prevention of infection by single strains, especially with the growing problem of resistance to available anti-viral drugs. A broad-spectrum antibody therapy would be of great benefit for protecting people at high risk of dying from influenza such as senior citizens. The immune system deteriorates with age, so the elderly are not adequately protected by current flu vaccines,” says Jaap Goudsmit, director of the Crucell Vaccine Institute and coauthor of the study.
Influenza B viruses are responsible for a significant proportion of the annual flu burden. The discovery of human monoclonal antibodies with broad activity against influenza B complements Crucell’s previous discoveries of broadly neutralizing antibodies against influenza A viruses. Importantly, it paves the way for development of a truly universal flu vaccine against influenza A and B, as well as new therapies.
The discovery reported in Science today fills the last gap in an antibody research field pioneered by Crucell. The new research paper documents the discovery of the first three human monoclonal antibodies (dubbed CR8033, CR8071 and CR9114) with the potential to combat any influenza B virus, together with results of studies in the laboratory and using mouse models of influenza.
The vast majority of antibodies the human immune system produces in response to an invading flu virus are relatively strain-specific. They recognize parts of the virus that rapidly mutate and change shape. In contrast, the novel broadly neutralizing antibodies identified in the new research combat a broad spectrum of virus strains by recognizing so-called ‘conserved epitopes’ on the viral surface: binding sites not prone to mutation and structural change.
Specifically, the novel antibodies protected the mice against normally lethal levels of exposure to influenza B viruses. The CR9114 antibodies had the broadest activity, protecting mice against both influenza A and B viruses.
The three novel influenza B antibodies recognize three distinct conserved epitopes on the surface of influenza B viruses. As Johnson & Johnson reported, these three sites of viral vulnerability can be used to guide the design of broadly protective vaccines. In particular, a vaccine that elicits antibodies targeting the CR9114 epitope may meet the ultimate goal of a universal vaccine providing long-lasting protection against all influenza A and B viruses.
Influenza A (type 1 and 2) and influenza B viruses are responsible for all cases of human flu. Influenza A viruses cause seasonal flu as well as influenza pandemics. Influenza B viruses are the major cause of seasonal influenza epidemics every two to four years, leading to substantial numbers of hospitalizations and deaths.
Every year, influenza viruses make millions of people severely ill, claim between 250,000 and 500,000 lives, and burden society with considerable economic losses and healthcare costs.1 The effectiveness of the currently available tools for fighting influenza—antiviral therapies and flu vaccines—is impaired by the ability of these viruses to mutate rapidly. Influenza viruses are increasingly showing resistance to antiviral drugs and vaccine manufacturers are continuously playing catch-up as new influenza strains emerge year by year.
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