Crucell and Scripps Research discover and describe broad-spectrum antibodies against influenza B, a crucial link in development of universal flu therapies and vaccine
Landmark finding published in Science
Leiden, the Netherlands (9 August, 2012) – 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.[i],[ii]
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. 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.
A Crucell-led scientific team was the first to report the identification of fully human broad-spectrum influenza A antibodies (PLoS ONE 3(12), December 2008). Soon after, studies performed at The Scripps Research Institute confirmed that the antibodies do indeed bind to ‘conserved epitopes’ (stable binding sites) on the main glycoprotein found on the viral surface (Science, February 2009). This binding location explained their unprecedented ability to neutralize different influenza strains. This initial discovery involved broad-spectrum antibodies against a range of influenza A type 1 viruses. Researchers from Scripps Research, Crucell and the University of Hong Kong went on to describe the first broadly neutralizing antibodies against influenza A type 2 viruses, as well (Science 333(6044), August 12, 2011).
The leading monoclonal antibodies from both of these novel classes are together able to neutralize essentially the entire spectrum of influenza A viruses. Crucell is developing these antibodies as immunotherapies for influenza A. Various research groups, including Crucell, also are exploring ways to induce such broadly neutralizing antibodies through vaccination.
“The identification and characterization of monoclonal antibodies with broad neutralizing activity against influenza B viruses, together with previously described broadly neutralizing antibodies against group 1 and group 2 influenza A viruses bring a universal therapy a step closer, and may guide the design of broadly protective vaccines. In particular, a vaccine that elicits antibodies targeting the CR9114 epitope may provide the ultimate goal of protection against all influenza A and influenza B viruses,”[iii] says Robert Friesen, deputy scientific director of the Crucell Vaccine Institute and a study coauthor.
1Source: Influenza (Seasonal) Fact Sheet, World Health Organization, 2009
Link to the Science publication announced on the Science Express web site:
Crucell is a biopharmaceutical company dedicated to bringing meaningful innovation to global health. Our teams focus on the discovery, development, manufacture and marketing of vaccines and antibodies to protect people worldwide from major health threats. Crucell’s specialty is fighting infectious diseases – a growing healthcare challenge. Innovation is the driving force behind our discovery and strong research and development pipeline, with promising candidates in pre-clinical and clinical development and patented technologies such as our PER.C6® human cell-line. In 2010 alone, Crucell distributed more than 105 million doses of vaccines in more than 100 countries around the world. We strive to do business ‘with a warm heart and a cool head’, generating sustainable profit in order to continue to innovate and give back to society. Crucell’s researchers are working on innovative immunization candidates to fight tuberculosis, malaria, HIV/AIDS, influenza, rabies, polio and several other diseases that are high on the list of global health problems. Meanwhile, we are already combating a dozen major infectious threats with our range marketed vaccines against paediatric, respiratory and travel or endemic infections: Quinvaxem®, a liquid pentavalent vaccine against five important childhood diseases; Epaxal®, the only aluminium-free hepatitis A vaccine; Hepavax-Gene®, a recombinant hepatitis B vaccine; Vivotif® and Dukoral®, oral vaccines against typhoid & cholera, and Inflexal® V, a virosomal adjuvanted vaccine against influenza.
Crucell is one of the Janssen Pharmaceutical Companies of Johnson & Johnson.
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[i] Lightly adapted from study abstract summary.
[ii] Manuscript, page 3, first paragraph
[iii] Manuscript, page 9, last paragraph