Abstract
BackgroundDuring the recent H1N1 influenza pandemic, excess morbidity and mortality was seen in young but not older adults suggesting that prior infection with influenza strains may have protected older subjects. In contrast, a history of recent seasonal trivalent vaccine in younger adults was not associated with protection.Methods and FindingsTo study hemagglutinin (HA) antibody responses in influenza immunization and infection, we have studied the day 7 plasma cell repertoires of subjects immunized with seasonal trivalent inactivated influenza vaccine (TIV) and compared them to the plasma cell repertoires of subjects experimentally infected (EI) with influenza H3N2 A/Wisconsin/67/2005. The majority of circulating plasma cells after TIV produced influenza-specific antibodies, while most plasma cells after EI produced antibodies that did not react with influenza HA. While anti-HA antibodies from TIV subjects were primarily reactive with single or few HA strains, anti-HA antibodies from EI subjects were isolated that reacted with multiple HA strains. Plasma cell-derived anti-HA antibodies from TIV subjects showed more evidence of clonal expansion compared with antibodies from EI subjects. From an H3N2-infected subject, we isolated a 4-member clonal lineage of broadly cross-reactive antibodies that bound to multiple HA subtypes and neutralized both H1N1 and H3N2 viruses. This broad reactivity was not detected in post-infection plasma suggesting this broadly reactive clonal lineage was not immunodominant in this subject.ConclusionThe presence of broadly reactive subdominant antibody responses in some EI subjects suggests that improved vaccine designs that make broadly reactive antibody responses immunodominant could protect against novel influenza strains.
Highlights
Influenza is a persistent threat to public health with seasonal influenza causing .200,000 hospitalizations and .35,000 deaths in the US annually [1,2]
The presence of broadly reactive subdominant antibody responses in some experimentally infected (EI) subjects suggests that improved vaccine designs that make broadly reactive antibody responses immunodominant could protect against novel influenza strains
Neutralizing antibodies reactive with multiple influenza subtypes have been isolated from phage-displayed libraries from uninfected subjects [9], those recovering from H5N1 influenza [10], and those vaccinated against seasonal influenza [11], but such antibodies are not immunodominant and generally are not found in plasma [12]
Summary
Influenza is a persistent threat to public health with seasonal influenza causing .200,000 hospitalizations and .35,000 deaths in the US annually [1,2]. In humans, boosting immunizations with trivalent inactivated influenza vaccine (TIV) are associated with the transient appearance of influenza-specific plasma cells/plasmablasts (hereafter termed plasma cells) in peripheral blood [6]. The majority of these plasma cells produce antibodies that bind HA and are both strain-specific and neutralizing [6]. During the recent H1N1 influenza pandemic, excess morbidity and mortality was seen in young but not older adults suggesting that prior infection with influenza strains may have protected older subjects. A history of recent seasonal trivalent vaccine in younger adults was not associated with protection
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
