TY - JOUR
T1 - Influenza Vaccination Results in Differential Hemagglutinin Stalk-Specific Fc-Mediated Functions in Individuals Living With or Without HIV
AU - Motsoeneng, Boitumelo M.
AU - Dhar, Nisha
AU - Nunes, Marta C.
AU - Krammer, Florian
AU - Madhi, Shabir A.
AU - Moore, Penny L.
AU - Richardson, Simone I.
N1 - Funding Information:
This sub-study is funded by the African Leadership in Vaccinology Expertise (ALIVE) research grant of the University of the Witwatersrand. BM is a recipient of bursaries from the South African National Research Foundation, the Poliomyelitis Research Foundation (grant 20/36) and the University of the Witwatersrand postgraduate merit award. PM is supported by the South African Research Chairs Initiative of the Department of Science and Innovation and National Research Foundation of South Africa, the SA Medical Research Council SHIP program (grant 98341), the Centre for the AIDS Program of Research (CAPRISA). SR is a L’Oreal/UNESCO Women in Science South Africa Young Talents awardee. The funders were not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication. Related research by the authors is conducted as part of the DST-NRF Centre of Excellence in HIV Prevention, which is supported by the Department of Science and Technology and the National Research Foundation. Generation of reagents in the Krammer laboratory was supported by Centers of Excellence for influenza Research and Response (75N93021C00014) and Collaborative Influenza Vaccine Innovation Centers (75N93019C00051).
Funding Information:
We thank Prof. Mark Hogarth (Burnet Institute, Melbourne, Australia) for the dimeric Fc?R constructs. The authors acknowledge Dr. Adriana Weinberg (University of Colorado, Denver) for testing of HAI titers. We thank all the trial participants, clinical staff and the Maternal Flu trial team.
Publisher Copyright:
Copyright © 2022 Motsoeneng, Dhar, Nunes, Krammer, Madhi, Moore and Richardson.
PY - 2022/4/19
Y1 - 2022/4/19
N2 - Influenza virus hemagglutinin (HA) stalk-specific antibodies have been shown to potently induce Fc-mediated effector functions which are important in protection from disease. In placebo-controlled maternal influenza (MatFlu) vaccination trials of pregnant women living with or without HIV, reduced risk of influenza illness was associated with high HA stalk antibody titers following trivalent inactivated vaccination (TIV). However, the mechanisms of immunity conferred by the HA stalk antibodies were not well understood. Here, we investigated HA stalk-specific Fc effector functions including antibody-dependent cellular phagocytosis (ADCP), antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent complement deposition (ADCD), and FcγRIIa and FcγRIIIa binding in response to seasonal influenza vaccination. These were measured pre- and 1-month post-vaccination in 141 HIV-uninfected women (67 TIV and 74 placebo recipients) and 119 women living with HIV (WLWH; 66 TIV and 53 placebo recipients). In contrast to HIV-uninfected women, where HA stalk-specific ADCP and FcγRIIa binding were significantly boosted, WLWH showed no increase in response to vaccination. HA stalk-specific ADCC potential and FcγRIIIa binding were not boosted regardless of HIV status but were higher in WLWH compared with HIV-uninfected women prior to vaccination. HA stalk-specific ADCD was significantly increased by vaccination in all women, but was significantly lower in the WLWH both pre- and post- vaccination. Co-ordination between HA stalk-specific ADCP and ADCD in WLWH was improved by vaccination. Fc polyfunctionality was enhanced by vaccination in HIV-uninfected women and driven by the HA stalk antibody titers. However, in the WLWH, higher pre-vaccination Fc polyfunctionality was maintained post-vaccination but was decoupled from titer. Overall, we showed differential regulation of Fc effector HA stalk responses, suggesting that HIV infection results in unique humoral immunity in response to influenza vaccination, with relevance for future strategies that aim to target the HA stalk in this population.
AB - Influenza virus hemagglutinin (HA) stalk-specific antibodies have been shown to potently induce Fc-mediated effector functions which are important in protection from disease. In placebo-controlled maternal influenza (MatFlu) vaccination trials of pregnant women living with or without HIV, reduced risk of influenza illness was associated with high HA stalk antibody titers following trivalent inactivated vaccination (TIV). However, the mechanisms of immunity conferred by the HA stalk antibodies were not well understood. Here, we investigated HA stalk-specific Fc effector functions including antibody-dependent cellular phagocytosis (ADCP), antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent complement deposition (ADCD), and FcγRIIa and FcγRIIIa binding in response to seasonal influenza vaccination. These were measured pre- and 1-month post-vaccination in 141 HIV-uninfected women (67 TIV and 74 placebo recipients) and 119 women living with HIV (WLWH; 66 TIV and 53 placebo recipients). In contrast to HIV-uninfected women, where HA stalk-specific ADCP and FcγRIIa binding were significantly boosted, WLWH showed no increase in response to vaccination. HA stalk-specific ADCC potential and FcγRIIIa binding were not boosted regardless of HIV status but were higher in WLWH compared with HIV-uninfected women prior to vaccination. HA stalk-specific ADCD was significantly increased by vaccination in all women, but was significantly lower in the WLWH both pre- and post- vaccination. Co-ordination between HA stalk-specific ADCP and ADCD in WLWH was improved by vaccination. Fc polyfunctionality was enhanced by vaccination in HIV-uninfected women and driven by the HA stalk antibody titers. However, in the WLWH, higher pre-vaccination Fc polyfunctionality was maintained post-vaccination but was decoupled from titer. Overall, we showed differential regulation of Fc effector HA stalk responses, suggesting that HIV infection results in unique humoral immunity in response to influenza vaccination, with relevance for future strategies that aim to target the HA stalk in this population.
KW - Fc effector functions
KW - HIV co-infection
KW - antibody- dependent cellular cytotoxicity (ADCC)
KW - antibody-dependent cellular phagocytosis (ADCP)
KW - antibody-dependent complement deposition (ADCD)
KW - hemagglutinin stalk antibodies
KW - influenza vaccination
UR - http://www.scopus.com/inward/record.url?scp=85129412694&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2022.873191
DO - 10.3389/fimmu.2022.873191
M3 - Article
C2 - 35514992
AN - SCOPUS:85129412694
SN - 1664-3224
VL - 13
JO - Frontiers in Immunology
JF - Frontiers in Immunology
M1 - 873191
ER -