In the Journals

Pre-emptively updating flu vaccine strains may improve effectiveness

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November 28, 2014

Forestalling virus evolution with pre-emptive influenza vaccine updates may improve vaccine effectiveness in people who were previously exposed, according to researchers.

“Faced with uncertainty about how and when the flu virus might evolve, it’s better to gamble than to be conservative,” study researcher Judith M. Fonville, PhD, a member of the WHO Collaborating Centre for Modeling, Evolution and Control of Emerging Infectious Diseases at the University of Cambridge, United Kingdom, told Infectious Disease News. “If you update early, you still stimulate protection against current strains — much worse is if you update too late.

Judy Fonville, PhD

Judith M. Fonville

“Rather than trying to play ‘catch-up,’ it’s better to anticipate and prepare for the likely next step of influenza evolution — and there is no penalty for doing it too soon. Rather than chasing influenza evolution, we can instead be ahead of the game.”

Antibody landscape

In collaboration with Samuel H. Wilks, PhD, research assistant at the WHO Collaborating Centre, and Derek J. Smith, PhD, professor of infectious disease informatics and director at the WHO Collaborating Centre, Fonville used a new computer-based method for mapping a person’s “antibody landscape.” The process analyzes antibody-mediated immunity to antigenically variable pathogens, which offers researchers much more information on how the human immune system responds to pathogens that evolve and reinfect people.

Sam Wilks, MPhil

Samuel H. Wilks

The influenza virus is challenging to vaccinate against because there are different circulating strains that evolve quickly, Fonville said.

Each February, WHO scientists pick the strain that will be used in the vaccine for the Northern Hemisphere. Because analyzing human immune responses is difficult — exposure histories are complex and often unknown — their selection is based on an analysis of immune responses in ferrets.

The challenge is the vaccine strain selected in February may have evolved by the time vaccination campaigns begin in October, reducing the efficacy of vaccine match.

“WHO selects a strain of flu using the best information available, but is faced with the possibility that the virus will evolve before the flu season,” Fonville said.

3-D image of immune profile

Researchers may have found a way to overcome these challenges. They mapped the antibody response to 81 influenza A(H3N2) viruses, covering 43 years of influenza virus evolution.

The resulting antibody landscapes offered detailed information on how the human immune system reacts to pathogens.

“This landscape visualizes an individual’s distinct immune profile like a 3-D landscape with mountains in areas of immune memory and valleys in unprotected areas,” Fonville said. “The technique enables a much greater understanding of how our immune system responds to pathogens such as flu that evolve and reinfect us.”

Analysis demonstrated that after infection or vaccination, there is an immune response to the infecting influenza strain as well as to all the strains the patient has previously encountered, according to Fonville.

“It is this broad recall of immunity, which we term the ‘back-boost,’ that is the basis for the proposed vaccine improvement,” she said. “When the vaccine strain is updated pre-emptively, we see that it still stimulates better protection against future viruses, yet this comes at no cost to the protection generated against currently circulating ones.”

Fonville and colleagues are organizing prospective clinical trials to study their pre-emptive vaccine update approach.

“Because the pre-emptive vaccine updates would not require any change to the current manufacturing process, its implementation is easy, and the only, but important, difference would be greater protection for the recipient,” she said. “We’re aiming to make an important vaccine even more effective.” – by Colleen Owens

Disclosure: See the study for a full list of relevant financial disclosures.

For more information:

Judith M. Fonville, PhD, can be reached at the department of zoology, University of Cambridge, Downing St., Cambridge CB2 3EJ; Email:

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