Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 109, Issue 23, Pages 9047-9052Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1118979109
Keywords
immunity; stalk; immunoglobulin; neutralization
Categories
Funding
- National Institutes of Health (NIH)/National Institute of Allergy and Infectious Diseases (NIAID) [U19-AI057266]
- American Recovery and Reinvestment Act Supplement [U19 AI057266-06S2]
- NIH/NIAID Center of Excellence for Influenza Research and Surveillance [HHSN266200700006C, HHSN266200500026C, 5U19AI062629-05]
- NIAID
- MRC [MC_G1001212, G0902266] Funding Source: UKRI
- Asthma UK [S06/001] Funding Source: researchfish
- Medical Research Council [G1000758, G0902266, MC_G1001212] Funding Source: researchfish
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We have previously shown that broadly neutralizing antibodies reactive to the conserved stem region of the influenza virus hemagglutinin ( HA) were generated in people infected with the 2009 pandemic H1N1 strain. Such antibodies are rarely seen in humans following infection or vaccination with seasonal influenza virus strains. However, the important question remained whether the inactivated 2009 pandemic H1N1 vaccine, like the infection, could also induce these broadly neutralizing antibodies. To address this question, we analyzed B-cell responses in 24 healthy adults immunized with the pandemic vaccine in 2009. In all cases, we found a rapid, predominantly IgG-producing vaccine-specific plasmablast response. Strikingly, the majority ( 25 of 28) of HA-specific monoclonal antibodies generated from the vaccine-specific plasmablasts neutralized more than one influenza strain and exhibited high levels of somatic hypermutation, suggesting they were derived from recall of B-cell memory. Indeed, memory B cells that recognized the 2009 pandemic H1N1 HA were detectable before vaccination not only in this cohort but also in samples obtained before the emergence of the pandemic strain. Three antibodies demonstrated extremely broad cross-reactivity and were found to bind the HA stem. Furthermore, one stem-reactive antibody recognized not only H1 and H5, but also H3 influenza viruses. This exceptional cross-reactivity indicates that antibodies capable of neutralizing most influenza subtypes might indeed be elicited by vaccination. The challenge now is to improve upon this result and design influenza vaccines that can elicit these broadly cross-reactive antibodies at sufficiently high levels to provide heterosubtypic protection.
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