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J Infect Dis
. 2023 Nov 20:jiad493.
doi: 10.1093/infdis/jiad493. Online ahead of print. Antibody-mediated Suppression Regulates the Humoral Immune Response to Influenza Vaccination in Humans
Xiuhua Lu 1 , Feng Liu 1 , Wen-Ping Tzeng 1 , Ian A York 1 , Terrence Tumpey 1 , Min Z Levine 1
Affiliations
Background: Pre-existing immunity, including memory B-cells and pre-existing antibodies, can modulate antibody responses to influenza in vivo to antigenically related antigens. We investigated whether pre-existing hemagglutination inhibition (HAI) antibodies targeting the K163 epitope on the hemagglutinin (K163-antibodies) could affect antibody responses following vaccination with A/California/07/2009-like (CA/09) A(H1N1)pdm09 influenza viruses in humans.
Methods: Pre- and post-vaccination sera collected from 300 adults (birth year:1961-1998) in 6 seasons (2010-2016) were analyzed using HAI assays with 2 reverse genetics viruses and A(H1N1) viruses circulated from 1977 to 2018. Antibody adsorption assays were used to verify the pre-existing K163-antibody-mediated suppression effect.
Results: Pre-existing K163-antibody titers of ≥80 affected HAI antibody responses following influenza vaccination containing CA/09-like antigens. At high K163-antibody concentrations (HAI antibody titers≥160), all HAI antibody responses were suppressed, while at moderate K163-antibody concentrations (HAI antibody titer=80), only K163-epitope-specific antibody responses were suppressed and novel HAI antibody responses targeting the non-K163-epitope(s) were induced by vaccination. Novel antibodies targeting non-K163 epitope(s) cross-reacted with newly emerging A(H1N1)pdm09 strains with a K163Q mutation, rather than historic 1977-2007 A(H1N1) viruses.
Conclusion: K163-antibody-mediated suppression shapes antibody responses to A(H1N1)pdm09 vaccination. Understanding how pre-existing antibodies suppress and redirect vaccine-induced antibody responses is of great importance to improve vaccine effectiveness.
Keywords: Influenza; Influenza A(H1N1) viruses; antibody-mediated suppression; epitope masking; influenza A(H1N1)pdm09 vaccine; original antigenic sin; pre-existing antibody.
. 2023 Nov 20:jiad493.
doi: 10.1093/infdis/jiad493. Online ahead of print. Antibody-mediated Suppression Regulates the Humoral Immune Response to Influenza Vaccination in Humans
Xiuhua Lu 1 , Feng Liu 1 , Wen-Ping Tzeng 1 , Ian A York 1 , Terrence Tumpey 1 , Min Z Levine 1
Affiliations
- PMID: 37981659
- DOI: 10.1093/infdis/jiad493
Background: Pre-existing immunity, including memory B-cells and pre-existing antibodies, can modulate antibody responses to influenza in vivo to antigenically related antigens. We investigated whether pre-existing hemagglutination inhibition (HAI) antibodies targeting the K163 epitope on the hemagglutinin (K163-antibodies) could affect antibody responses following vaccination with A/California/07/2009-like (CA/09) A(H1N1)pdm09 influenza viruses in humans.
Methods: Pre- and post-vaccination sera collected from 300 adults (birth year:1961-1998) in 6 seasons (2010-2016) were analyzed using HAI assays with 2 reverse genetics viruses and A(H1N1) viruses circulated from 1977 to 2018. Antibody adsorption assays were used to verify the pre-existing K163-antibody-mediated suppression effect.
Results: Pre-existing K163-antibody titers of ≥80 affected HAI antibody responses following influenza vaccination containing CA/09-like antigens. At high K163-antibody concentrations (HAI antibody titers≥160), all HAI antibody responses were suppressed, while at moderate K163-antibody concentrations (HAI antibody titer=80), only K163-epitope-specific antibody responses were suppressed and novel HAI antibody responses targeting the non-K163-epitope(s) were induced by vaccination. Novel antibodies targeting non-K163 epitope(s) cross-reacted with newly emerging A(H1N1)pdm09 strains with a K163Q mutation, rather than historic 1977-2007 A(H1N1) viruses.
Conclusion: K163-antibody-mediated suppression shapes antibody responses to A(H1N1)pdm09 vaccination. Understanding how pre-existing antibodies suppress and redirect vaccine-induced antibody responses is of great importance to improve vaccine effectiveness.
Keywords: Influenza; Influenza A(H1N1) viruses; antibody-mediated suppression; epitope masking; influenza A(H1N1)pdm09 vaccine; original antigenic sin; pre-existing antibody.