tetano
Editor, Senior Moderator
April 2013, doi: 10.1128/JVI.00641-13
Chimeric hemagglutinin influenza virus vaccine constructs elicit broadly-protective stalk-specific antibodies
Florian Krammer1,
Natalie Pica1,3,
Rong Hai1,
Irina Margine1,3 and
Peter Palese1,2*
+ Author Affiliations
1Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
2Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA
3Graduate School of Biological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA
ABSTRACT
Current influenza virus vaccine strategies stimulate immune responses towards the globular head domain of the hemagglutinin protein in order to inhibit key steps of the virus lifecycle. Because this domain is highly variable across strains, new vaccine formulations are required in most years. Here we demonstrate a novel vaccine strategy that generates immunity to the highly conserved stalk domain, using chimeric hemagglutinin constructs that express unique head and stalk combinations. By repeatedly immunizing with constructs that express the same stalk but an irrelevant head, we specifically stimulate a stalk-directed response that provides broad-based heterologous and heterosubtypic immunity in mice. Notably, our vaccination scheme provides a universal vaccine approach that protects against challenge with an H5 subtyped virus. Furthermore, through in vivo studies using passively transferred antibodies or depletion of CD8+ T cells, we demonstrate the critical role that humoral mechanisms of immunity play in the protection observed. The present data suggest that a vaccine strategy based on the stalk domain of the hemagglutinin protein could be used in humans to broadly protect against a variety of influenza virus subtypes.
http://jvi.asm.org/content/early/2013/04/04/JVI.00641-13.abstract
Chimeric hemagglutinin influenza virus vaccine constructs elicit broadly-protective stalk-specific antibodies
Florian Krammer1,
Natalie Pica1,3,
Rong Hai1,
Irina Margine1,3 and
Peter Palese1,2*
+ Author Affiliations
1Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
2Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA
3Graduate School of Biological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA
ABSTRACT
Current influenza virus vaccine strategies stimulate immune responses towards the globular head domain of the hemagglutinin protein in order to inhibit key steps of the virus lifecycle. Because this domain is highly variable across strains, new vaccine formulations are required in most years. Here we demonstrate a novel vaccine strategy that generates immunity to the highly conserved stalk domain, using chimeric hemagglutinin constructs that express unique head and stalk combinations. By repeatedly immunizing with constructs that express the same stalk but an irrelevant head, we specifically stimulate a stalk-directed response that provides broad-based heterologous and heterosubtypic immunity in mice. Notably, our vaccination scheme provides a universal vaccine approach that protects against challenge with an H5 subtyped virus. Furthermore, through in vivo studies using passively transferred antibodies or depletion of CD8+ T cells, we demonstrate the critical role that humoral mechanisms of immunity play in the protection observed. The present data suggest that a vaccine strategy based on the stalk domain of the hemagglutinin protein could be used in humans to broadly protect against a variety of influenza virus subtypes.
http://jvi.asm.org/content/early/2013/04/04/JVI.00641-13.abstract