Broadly cross-reactive antibodies dominate the human B cell response against 2009 pandemic H1N1 influenza virus infection

Emory Vaccine Center, School of Medicine, Emory University, Atlanta, GA 30322, USA.
Journal of Experimental Medicine (Impact Factor: 13.91). 02/2011; 208(1):181-93. DOI: 10.1084/jem.20101352
Source: PubMed

ABSTRACT The 2009 pandemic H1N1 influenza pandemic demonstrated the global health threat of reassortant influenza strains. Herein, we report a detailed analysis of plasmablast and monoclonal antibody responses induced by pandemic H1N1 infection in humans. Unlike antibodies elicited by annual influenza vaccinations, most neutralizing antibodies induced by pandemic H1N1 infection were broadly cross-reactive against epitopes in the hemagglutinin (HA) stalk and head domain of multiple influenza strains. The antibodies were from cells that had undergone extensive affinity maturation. Based on these observations, we postulate that the plasmablasts producing these broadly neutralizing antibodies were predominantly derived from activated memory B cells specific for epitopes conserved in several influenza strains. Consequently, most neutralizing antibodies were broadly reactive against divergent H1N1 and H5N1 influenza strains. This suggests that a pan-influenza vaccine may be possible, given the right immunogen. Antibodies generated potently protected and rescued mice from lethal challenge with pandemic H1N1 or antigenically distinct influenza strains, making them excellent therapeutic candidates.

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Available from: Aneesh K Mehta, Aug 14, 2015
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    • "Recent studies aiming to characterize conserved epitopes of influenza virus revealed that specific regions in the HA stalk domain are highly preserved both in the structure and the sequence among various subtypes of viruses. It has been discovered that neutralizing antibodies to the HA stalk domain can be found after influenza infection (Wrammert et al., 2011) and vaccination (Corti et al., 2010). These anti-stalk antibodies demonstrate cross-reactivity between HAs of many strains from group 1 as well as from group 2 and it has been shown * e-mail: "
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    • "Thus, in individuals who were already sensitized due to cross-neutralization, subsequent challenges with similar epitopes led to extend the immune arsenal against the same epitope by recruiting other compartments of the immune system than specific antibodies. Finally, all together, these findings reinforce the general idea that multiple vaccination leads to a broader immune repertoire than the one theoretically expected by influenza vaccine strains and this due to cross-neutralizing determinants [14] and restimulation of memory cellular responses to conserved region of influenza viruses [16]. Moreover, in case of new contact with influenza strains previously encountered, we can speculate that the immune system is able to extend its response to other immune components instead of over stimulate the already sensibilized compartment. "
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