Katherine V Williams1, Bo Zhai2, John F Alcorn3, Mary Patricia Nowalk4, Min Z Levine5, Sara S Kim6, Brendan Flannery7, Krissy Moehling Geffel8, Amanda Jaber Merranko9, Jennifer P Nagg10, Mark Collins11, Michael Susick12, Karen S Clarke13, Richard K Zimmerman14, Judith M Martin15. 1. Department of Family Medicine, University of Pittsburgh, 4420 Bayard Street, Suite 520, Pittsburgh, PA 15260, USA. Electronic address: kvw3@pitt.edu. 2. Department of Immunology, University of Pittsburgh, 9127 Rangos Research Center, 4401 Penn Avenue, Pittsburgh, PA 15224 USA. Electronic address: bo.zhai@chp.edu. 3. Department of Immunology, University of Pittsburgh, 9127 Rangos Research Center, 4401 Penn Avenue, Pittsburgh, PA 15224 USA; Department of Pediatrics, University of Pittsburgh, 3520 Fifth Avenue, Pittsburgh, PA 15213, USA. Electronic address: John.Alcorn@chp.edu. 4. Department of Family Medicine, University of Pittsburgh, 4420 Bayard Street, Suite 520, Pittsburgh, PA 15260, USA. Electronic address: tnowalk@pitt.edu. 5. National Center Immunizations and Respiratory Disease, Center for Disease Control and Prevention, Atlanta, GA, USA. Electronic address: mwl2@cdc.gov. 6. National Center Immunizations and Respiratory Disease, Center for Disease Control and Prevention, Atlanta, GA, USA. Electronic address: omy1@cdc.gov. 7. National Center Immunizations and Respiratory Disease, Center for Disease Control and Prevention, Atlanta, GA, USA. Electronic address: bif4@cdc.gov. 8. Department of Family Medicine, University of Pittsburgh, 4420 Bayard Street, Suite 520, Pittsburgh, PA 15260, USA. Electronic address: kkm17@pitt.edu. 9. Falk Pharmacy, University of Pittsburgh Medical Center (UPMC), 3601 Fifth Avenue, Pittsburgh, PA 15213, USA. Electronic address: jabera@upmc.edu. 10. Department of Pediatrics, University of Pittsburgh, 3520 Fifth Avenue, Pittsburgh, PA 15213, USA. Electronic address: Jennifer.Nagg@chp.edu. 11. Department of Family Medicine, University of Pittsburgh, 4420 Bayard Street, Suite 520, Pittsburgh, PA 15260, USA. Electronic address: mjc@pitt.edu. 12. Department of Family Medicine, University of Pittsburgh, 4420 Bayard Street, Suite 520, Pittsburgh, PA 15260, USA. Electronic address: susickm@upmc.edu. 13. Department of Family Medicine, University of Pittsburgh, 4420 Bayard Street, Suite 520, Pittsburgh, PA 15260, USA. Electronic address: KAC373@pitt.edu. 14. Department of Family Medicine, University of Pittsburgh, 4420 Bayard Street, Suite 520, Pittsburgh, PA 15260, USA. Electronic address: zimmrk@upmc.edu. 15. Department of Pediatrics, University of Pittsburgh, 3520 Fifth Avenue, Pittsburgh, PA 15213, USA. Electronic address: martinju@pitt.edu.
Abstract
BACKGROUND: Hemagglutination inhibition (HAI) titers to the live-attenuated influenza vaccine (LAIV4) are typically lower than its counterpart egg-based inactivated influenza vaccines (IIV). Similar comparisons have not been made between LAIV4 and the 4-strain, cell-culture inactivated influenza vaccine (ccIIV4). We compared healthy children's and young adults' HAI titers against the 2019-2020 LAIV4 and ccIIV4. METHODS: Participants aged 4-21 years were randomized 1:1 to receive ccIIV4 (n = 100) or LAIV4 (n = 98). Blood was drawn prevaccination and on day 28 (21-35) post vaccination. HAI assays against egg-grown A/H1N1, A/H3N2, both vaccine B strains and cell-grown A/H3N2 antigens were conducted. Primary outcomes were geometric mean titers (GMT) and geometric mean fold rise (GMFR) in titers. RESULTS: GMTs to A/H1N1, A/H3N2 and B/Victoria increased following both ccIIV and LAIV and to B/Yamagata following ccIIV (p < 0.05). The GMFR range was 2.4-3.0 times higher for ccIIV4 than for LAIV4 (p < 0.001). Within vaccine types, egg-grown A/H3N2 GMTs were higher (p < 0.05) than cell-grown GMTs [ccIIV4 day 28: egg = 205 (95% CI: 178-237); cell = 136 (95% CI:113-165); LAIV4 day 28: egg = 96 (95% CI: 83-112); cell = 63 (95% CI: 58-74)]. The GMFR to A/H3N2 cell-grown and egg-grown antigens were similar. Pre-vaccination titers inversely predicted GMFR. CONCLUSION: The HAI response to ccIIV4 was greater than LAIV4 in this study of mostly older children, and day 0 HAI titers inversely predicted GMFR for both vaccines. Lower prevaccination titers were associated with greater GMFR in both vaccine groups.
BACKGROUND: Hemagglutination inhibition (HAI) titers to the live-attenuated influenza vaccine (LAIV4) are typically lower than its counterpart egg-based inactivated influenza vaccines (IIV). Similar comparisons have not been made between LAIV4 and the 4-strain, cell-culture inactivated influenza vaccine (ccIIV4). We compared healthy children's and young adults' HAI titers against the 2019-2020 LAIV4 and ccIIV4. METHODS: Participants aged 4-21 years were randomized 1:1 to receive ccIIV4 (n = 100) or LAIV4 (n = 98). Blood was drawn prevaccination and on day 28 (21-35) post vaccination. HAI assays against egg-grown A/H1N1, A/H3N2, both vaccine B strains and cell-grown A/H3N2 antigens were conducted. Primary outcomes were geometric mean titers (GMT) and geometric mean fold rise (GMFR) in titers. RESULTS: GMTs to A/H1N1, A/H3N2 and B/Victoria increased following both ccIIV and LAIV and to B/Yamagata following ccIIV (p < 0.05). The GMFR range was 2.4-3.0 times higher for ccIIV4 than for LAIV4 (p < 0.001). Within vaccine types, egg-grown A/H3N2 GMTs were higher (p < 0.05) than cell-grown GMTs [ccIIV4 day 28: egg = 205 (95% CI: 178-237); cell = 136 (95% CI:113-165); LAIV4 day 28: egg = 96 (95% CI: 83-112); cell = 63 (95% CI: 58-74)]. The GMFR to A/H3N2 cell-grown and egg-grown antigens were similar. Pre-vaccination titers inversely predicted GMFR. CONCLUSION: The HAI response to ccIIV4 was greater than LAIV4 in this study of mostly older children, and day 0 HAI titers inversely predicted GMFR for both vaccines. Lower prevaccination titers were associated with greater GMFR in both vaccine groups.
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