Kelsey Florek1, James Mutschler2, Huong Q McLean3, Jennifer P King3, Brendan Flannery4, Edward A Belongia5, Thomas C Friedrich6. 1. Wisconsin State Laboratory of Hygiene, Madison, WI 53714, USA. 2. Department of Pathobiological Sciences, University of Wisconsin School of Veterinary Medicine, Madison, WI 53706, USA. 3. Center for Clinical Epidemiology and Population Health, Marshfield Clinic Research Institute, 1000 North Oak Ave, Marshfield 54449, WI, USA. 4. Centers for Disease Control and Prevention, 1600 Clifton Rd, Atlanta 30333, GA, USA. 5. Center for Clinical Epidemiology and Population Health, Marshfield Clinic Research Institute, 1000 North Oak Ave, Marshfield 54449, WI, USA. Electronic address: belongia.edward@marshfieldclinic.org. 6. Department of Pathobiological Sciences, University of Wisconsin School of Veterinary Medicine, Madison, WI 53706, USA; Wisconsin National Primate Research Center, Madison, WI 53715, USA. Electronic address: thomasf@primate.wisc.edu.
Abstract
BACKGROUND: Seasonal influenza vaccines aim to induce strain-specific neutralizing antibodies. Non-neutralizing antibodies may be more broadly cross-reactive and still protect through mechanisms including antibody-dependent cell-mediated cytotoxicity (ADCC). Influenza vaccines may stimulate ADCC antibodies in adults, but whether they do so in children is unknown. Here we examined how vaccination affects cross-reactive ADCC antibody responses in children after receipt ofinactivated trivalent vaccine (IIV3) or quadrivalent live-attenuated vaccine (LAIV4). METHODS:Children aged 5-17 were recruited in fall 2014 to provide pre- and post-vaccination serum samples. Children aged 5-9 received LAIV4 based on then-current recommendation, and older children were randomly assigned to IIV3 or LAIV4. We used microtiter-plate-based flow cytometry with an NK cell line to examine ADCC antibody responses to the 2014-15 H3N2 vaccine component (A/Texas/50/2012 [TX12]) and a drifted strain, A/Switzerland/9715293/2013 (SW13). Responses were stratified by two-season (2013-14 and 2014-15) vaccine sequence. RESULTS: Eighty-five children received LAIV4 and 45 received IIV3. Prevaccination ADCC activity was highest in children who had received any vaccine in the prior season. Increase in ADCC antibody responses against the vaccine strain TX12 following vaccination was greatest for participants who received IIV3 in 2014-15 and LAIV4 in the prior season (geometric mean fold rise [MFR] = 1.6, 95% CI. 1.23-2.11). This group also had a detectable ADCC response to the drifted SW13 strain. There was a modest ADCC response against SW13 in LAIV4 recipients who were unvaccinated in the previous season (MFR = 1.18, 95% CI 1.10-1.25). There were no significant changes in 2014-15 ADCC response to vaccination among children who had received IIV3 in 2013-14. CONCLUSIONS: Vaccinating children with IIV3 after prior receipt of LAIV4 generated a modest increase in ADCC antibodies, including some cross-reactivity with an emerging drift variant. Other vaccine-induced ADCC responses were minimal and not affected by vaccine type or sequence.
RCT Entities:
BACKGROUND: Seasonal influenza vaccines aim to induce strain-specific neutralizing antibodies. Non-neutralizing antibodies may be more broadly cross-reactive and still protect through mechanisms including antibody-dependent cell-mediated cytotoxicity (ADCC). Influenza vaccines may stimulate ADCC antibodies in adults, but whether they do so in children is unknown. Here we examined how vaccination affects cross-reactive ADCC antibody responses in children after receipt of inactivated trivalent vaccine (IIV3) or quadrivalent live-attenuated vaccine (LAIV4). METHODS:Children aged 5-17 were recruited in fall 2014 to provide pre- and post-vaccination serum samples. Children aged 5-9 received LAIV4 based on then-current recommendation, and older children were randomly assigned to IIV3 or LAIV4. We used microtiter-plate-based flow cytometry with an NK cell line to examine ADCC antibody responses to the 2014-15 H3N2 vaccine component (A/Texas/50/2012 [TX12]) and a drifted strain, A/Switzerland/9715293/2013 (SW13). Responses were stratified by two-season (2013-14 and 2014-15) vaccine sequence. RESULTS: Eighty-five children received LAIV4 and 45 received IIV3. Prevaccination ADCC activity was highest in children who had received any vaccine in the prior season. Increase in ADCC antibody responses against the vaccine strain TX12 following vaccination was greatest for participants who received IIV3 in 2014-15 and LAIV4 in the prior season (geometric mean fold rise [MFR] = 1.6, 95% CI. 1.23-2.11). This group also had a detectable ADCC response to the drifted SW13 strain. There was a modest ADCC response against SW13 in LAIV4 recipients who were unvaccinated in the previous season (MFR = 1.18, 95% CI 1.10-1.25). There were no significant changes in 2014-15 ADCC response to vaccination among children who had received IIV3 in 2013-14. CONCLUSIONS: Vaccinating children with IIV3 after prior receipt of LAIV4 generated a modest increase in ADCC antibodies, including some cross-reactivity with an emerging drift variant. Other vaccine-induced ADCC responses were minimal and not affected by vaccine type or sequence.
Authors: Jennifer P King; Huong Q McLean; Jennifer K Meece; Min Z Levine; Sarah M Spencer; Brendan Flannery; Edward A Belongia Journal: Vaccine Date: 2018-02-21 Impact factor: 3.641
Authors: Michael D Alpert; Lisa N Heyer; David E J Williams; Jackson D Harvey; Thomas Greenough; Maria Allhorn; David T Evans Journal: J Virol Date: 2012-08-29 Impact factor: 5.103
Authors: Rory D de Vries; Nella J Nieuwkoop; Mark Pronk; Erwin de Bruin; Geert Leroux-Roels; Elisabeth G W Huijskens; Rob S van Binnendijk; Florian Krammer; Marion P G Koopmans; Guus F Rimmelzwaan Journal: Vaccine Date: 2016-11-30 Impact factor: 3.641
Authors: Sinthujan Jegaskanda; Thakshila H Amarasena; Karen L Laurie; Hyon-Xhi Tan; Jeff Butler; Matthew S Parsons; Sheilajen Alcantara; Janka Petravic; Miles P Davenport; Aeron C Hurt; Patrick C Reading; Stephen J Kent Journal: J Virol Date: 2013-10-09 Impact factor: 5.103
Authors: Kelsey R Florek; Attapon Kamlangdee; James P Mutschler; Brock Kingstad-Bakke; Nancy Schultz-Darken; Karl W Broman; Jorge E Osorio; Thomas C Friedrich Journal: PLoS One Date: 2017-08-03 Impact factor: 3.240
Authors: Huong Q McLean; Jennifer P King; Pamela Talley; Brendan Flannery; Sarah Spencer; Min Z Levine; Thomas C Friedrich; Edward A Belongia Journal: J Pediatric Infect Dis Soc Date: 2020-04-30 Impact factor: 3.164
Authors: Fernanda Ana-Sosa-Batiz; Hillary Vanderven; Sinthujan Jegaskanda; Angus Johnston; Steven Rockman; Karen Laurie; Ian Barr; Patrick Reading; Marit Lichtfuss; Stephen J Kent Journal: PLoS One Date: 2016-04-28 Impact factor: 3.240
Authors: Xuemin Chen; He-Ying Sun; Chun Yi Lee; Christina A Rostad; Jessica Trost; Rodrigo B Abreu; Michael A Carlock; Jason R Wilson; Shane Gansebom; Ted M Ross; David A Steinhauer; Evan J Anderson; Larry J Anderson Journal: Virology Date: 2022-02-24 Impact factor: 3.513