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Breakthrough Flu Vaccine Inhibited by Pre-existing Antibodies

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A breakthrough universal flu vaccine targeted to conserved regions of the influenza virus is blocked from boosting immune response by antibodies present from previous infections and vaccinations. 

Zarnitsyna et al. from Emory University and the Emory Vaccine Centre in Georgia, US, reported in PLOS Pathogens last month on insights from the interrogation of qualitative mathematical models of the dynamics of antibody responses to multiple epitopes on the new strain in the case of pre-immunity from previous strains’ exposure. Using human vaccination trial data, they explained why a prospective universal influenza vaccine isn’t more effective. 

Seasonal and pandemic influenza are a major public health concern; a universal flu vaccine that is effective long term against a broad range of flu strains would be a major breakthrough. The classic flu vaccine is targeted against the head region of the major influenza virus surface molecule hemagglutinin (HA).  The vaccine requires frequent updating in order to protect against small changes in the virus from one year to the next as well as larger changes associated with the emergence of new strains from zoonotic reservoirs that cause pandemics

Recent animal studies show that it is possible to generate high levels of antibody to the highly conserved stem region of HA, but only very limited boosting of these antibodies was observed in humans. "We used unique human vaccination data that separately measured antibody responses to each head and stem of the HA before and after vaccination for every individual," Veronika Zarnitsyna said. "That allowed us to discriminate between different biological mechanisms that might limit boosting of antibodies to the conserved stem region". Zarnitsyna et al. found that effective boosting of human responses to the stem of HA was attenuated by steric hindrance from the pre-existing antibodies, and suggested that significantly higher doses of vaccine could be required to overcome this. Understanding and devising ways round this masking effect is critical and could lead the way to a new generation of more effective, cross-protective vaccines.