[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]
JCI Insight. 2019 Nov 14;4(22). pii: 129035. doi: 10.1172/jci.insight.129035.
Hemagglutinin head-specific responses dominate over stem-specific responses following prime boost with mismatched vaccines.
Jegaskanda S1,2, Andrews SF3, Wheatley AK2,3, Yewdell JW4, McDermott AB3, Subbarao K1.
Author information: 1 Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA. 2 Department of Microbiology and Immunology, University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia. 3 Vaccine Research Center and. 4 Laboratory of Viral Diseases, National Institute of Allergy and Infectious Disease, NIH, Bethesda, Maryland, USA.
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.
KEYWORDS: Infectious disease; Influenza; Vaccines
PMID: 31723058 DOI: 10.1172/jci.insight.129035
Keywords: Influenza A; H5N1; Vaccines.