Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising/recruitment
  • Contact
  • Current Issue
  • Past Issues
  • By specialty
    • COVID-19
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All ...
  • Videos
  • Collections
    • Technical Advances
    • Clinical Medicine
    • Reviews
    • Editorials
    • Perspectives
    • Top read articles
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • In-Press Preview
  • Concise Communication
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising/recruitment
  • Contact
Hemagglutinin head-specific responses dominate over stem-specific responses following prime boost with mismatched vaccines
Sinthujan Jegaskanda, … , Adrian B. McDermott, Kanta Subbarao
Sinthujan Jegaskanda, … , Adrian B. McDermott, Kanta Subbarao
Published November 14, 2019
Citation Information: JCI Insight. 2019;4(22):e129035. https://doi.org/10.1172/jci.insight.129035.
View: Text | PDF
Research Article Infectious disease Vaccines

Hemagglutinin head-specific responses dominate over stem-specific responses following prime boost with mismatched vaccines

  • Text
  • PDF
Abstract

Broadly neutralizing Abs targeting the HA stem can provide broad protection against different influenza subtypes, raising the question of how best to elicit such Abs. We have previously demonstrated that vaccination with pandemic live-attenuated influenza vaccine (pLAIV) establishes immune memory for HA head-specific Abs. Here, we determine the extent to which matched versus mismatched LAIV-inactivated subunit vaccine (IIV) prime-boost vaccination elicits stem-specific memory B cells and Abs. We vaccinated African green monkeys with H5N1 pLAIV-pIIV or H5N1 pLAIV followed by seasonal IIV (sIIV) or with H5N1 pLAIV alone and measured Abs and HA-specific B cell responses. While we observed an increase in stem-specific memory B cells, head-specific memory B cell responses were substantially higher than stem-specific responses and were dominant even following boost with mismatched IIV. Neutralizing Abs against heterologous influenza viruses were undetectable. Head-specific B cells from draining lymph nodes exhibited germinal center markers, while stem-specific B cells found in the spleen and peripheral blood did not. Thus, although mismatched prime-boost generated a pool of stem-specific memory B cells, head-specific B cells and serum Abs substantially dominated the immune response. These findings have implications for including full-length native HA in prime-boost strategies intended to induce stem-specific Abs for universal influenza vaccination.

Authors

Sinthujan Jegaskanda, Sarah F. Andrews, Adam K. Wheatley, Jonathan W. Yewdell, Adrian B. McDermott, Kanta Subbarao

×

Full Text PDF | Download (5.68 MB)


Copyright © 2021 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts