Most monoclonal antibodies (mAbs) generated from humans infected or vaccinated with the 2009 pandemic H1N1 (pdmH1N1) influenza virus targeted the hemagglutinin (HA) stem. These anti-HA stem mAbs mostly used IGHV1-69 and bound readily to epitopes on the conventional seasonal influenza and pdmH1N1 vaccines. The anti-HA stem mAbs neutralized pdmH1N1, seasonal influenza H1N1 and avian H5N1 influenza viruses by inhibiting HA-mediated fusion of membranes and protected against and treated heterologous lethal infections in mice with H5N1 influenza virus. This demonstrated that therapeutic mAbs could be generated a few months after the new virus emerged. Human immunization with the pdmH1N1 vaccine induced circulating antibodies that when passively transferred, protected mice from lethal, heterologous H5N1 influenza infections. We observed that the dominant heterosubtypic antibody response against the HA stem correlated with the relative absence of memory B cells against the HA head of pdmH1N1, thus enabling the rare heterosubtypic memory B cells induced by seasonal influenza and specific for conserved sites on the HA stem to compete for T-cell help. These results support the notion that broadly protective antibodies against influenza would be induced by successive vaccination with conventional influenza vaccines based on subtypes of HA in viruses not circulating in humans.
Keywords: pandemic H1N1 influenza, vaccines, cross-protective antibodies, heterosubtypic, plasmablasts, memory B cells, competition for T-cell help, hemagglutinin
Citation: Thomson CA, Wang Y, Jackson LM, Olson M, Wang W, Liavonchanka A, Keleta L, Silva V, Diederich S, Jones RB, Gubbay J, Pasick J, Petric M, Jean F, Allen VG, Brown EG, Rini JM and Schrader JW (2012) Pandemic H1N1 influenza infection and vaccination in humans induces cross-protective antibodies that target the hemagglutinin stem. Front. Immun. 3:87. doi: 10.3389/fimmu.2012.00087
Received: 16 February 2012; Paper pending published: 06 March 2012;
Accepted: 04 April 2012; Published online: 08 May 2012.
Edited by:Harry W. Schroeder, University of Alabama at Birmingham, USA
Reviewed by:Patrick C. Wilson, University of Chicago, USA
Copyright: © 2012 Thomson, Wang, Jackson, Olson, Wang, Liavonchanka, Keleta, Silva, Diederich, Jones, Gubbay, Pasick, Petric, Jean, Allen, Brown, Rini and Schrader. This is an open-access article distributed under the terms of the Creative Commons Attribution Non Commercial License, which permits non-commercial use, distribution, and reproduction in other forums, provided the original authors and source are credited.
*Correspondence: J. W. Schrader, The Biomedical Research Centre, University of British Columbia, 2222 Health Sciences Mall, Vancouver, BC, Canada V6T 1Z3. e-mail: email@example.com
†C. A. Thomson and Y. Wang have contributed equally to this work.