TY - JOUR
T1 - Comparison of A(H3N2) neutralizing antibody responses elicited by 2018–2019 season quadrivalent influenza vaccines derived from eggs, cells, and recombinant hemagglutinin
AU - Wang, Wei
AU - Alvarado-Facundo, Esmeralda
AU - Vassell, Russell
AU - Collins, Limone
AU - Colombo, Rhonda E.
AU - Ganesan, Anuradha
AU - Geaney, Casey
AU - Hrncir, David
AU - Lalani, Tahaniyat
AU - Markelz, Ana Elizabeth
AU - Maves, Ryan C.
AU - McClenathan, Bruce
AU - Mende, Katrin
AU - Richard, Stephanie A.
AU - Schofield, Christina
AU - Seshadri, Srihari
AU - Spooner, Christina
AU - Utz, Gregory C.
AU - Warkentien, Tyler E.
AU - Levine, Min
AU - Coles, Christian L.
AU - Burgess, Timothy H.
AU - Eichelberger, Maryna
AU - Weiss, Carol D.
N1 - Publisher Copyright:
© 2021 Oxford University Press. All rights reserved.
PY - 2021/12/1
Y1 - 2021/12/1
N2 - Background. Low vaccine effectiveness against A(H3N2) influenza in seasons with little antigenic drift has been attributed to substitutions in hemagglutinin (HA) acquired during vaccine virus propagation in eggs. Clinical trials comparing recombinant HA vaccine (rHA) and cell-derived inactivated influenza vaccine (IIV) to egg-derived IIVs provide opportunities to assess how egg-adaptive substitutions influence HA immunogenicity. Methods. Neutralization titers in pre- and postimmunization sera from 133 adults immunized with 1 of 3 types of influenza vaccines in a randomized, open-label trial during the 2018–2019 influenza season were measured against egg- and cell-derived A/Singapore/INFIMH-16-0019/2016-like and circulating A(H3N2) influenza viruses using HA pseudoviruses. Results. All vaccines elicited neutralizing antibodies to all H3 vaccine antigens, but the rHA vaccine elicited the highest titers and seroconversion rates against all strains tested. Egg- and cell-derived IIVs elicited responses similar to each other. Preimmunization titers against H3 HA pseudoviruses containing egg-adaptive substitutions T160K and L194P were high, but lower against H3 HA pseudoviruses without those substitutions. All vaccines boosted neutralization titers against HA pseudoviruses with egg-adaptive substitutions, but poorly neutralized wild-type 2019–2020 A/Kansas/14/2017 (H3N2) HA pseudoviruses. Conclusion. Egg- and cell-derived 2018–2019 season influenza vaccines elicited similar neutralization titers and response rates, indicating that the cell-derived vaccine did not improve immunogenicity against the A(H3N2) viruses. The higher responses after rHA vaccination may be due to its higher HA content. All vaccines boosted titers to HA with egg-adaptive substitutions, suggesting boosting from past antigens or better exposure of HA epitopes. Studies comparing immunogenicity and effectiveness of different influenza vaccines across many seasons are needed.
AB - Background. Low vaccine effectiveness against A(H3N2) influenza in seasons with little antigenic drift has been attributed to substitutions in hemagglutinin (HA) acquired during vaccine virus propagation in eggs. Clinical trials comparing recombinant HA vaccine (rHA) and cell-derived inactivated influenza vaccine (IIV) to egg-derived IIVs provide opportunities to assess how egg-adaptive substitutions influence HA immunogenicity. Methods. Neutralization titers in pre- and postimmunization sera from 133 adults immunized with 1 of 3 types of influenza vaccines in a randomized, open-label trial during the 2018–2019 influenza season were measured against egg- and cell-derived A/Singapore/INFIMH-16-0019/2016-like and circulating A(H3N2) influenza viruses using HA pseudoviruses. Results. All vaccines elicited neutralizing antibodies to all H3 vaccine antigens, but the rHA vaccine elicited the highest titers and seroconversion rates against all strains tested. Egg- and cell-derived IIVs elicited responses similar to each other. Preimmunization titers against H3 HA pseudoviruses containing egg-adaptive substitutions T160K and L194P were high, but lower against H3 HA pseudoviruses without those substitutions. All vaccines boosted neutralization titers against HA pseudoviruses with egg-adaptive substitutions, but poorly neutralized wild-type 2019–2020 A/Kansas/14/2017 (H3N2) HA pseudoviruses. Conclusion. Egg- and cell-derived 2018–2019 season influenza vaccines elicited similar neutralization titers and response rates, indicating that the cell-derived vaccine did not improve immunogenicity against the A(H3N2) viruses. The higher responses after rHA vaccination may be due to its higher HA content. All vaccines boosted titers to HA with egg-adaptive substitutions, suggesting boosting from past antigens or better exposure of HA epitopes. Studies comparing immunogenicity and effectiveness of different influenza vaccines across many seasons are needed.
KW - Egg-adaptive mutations
KW - Hemagglutinin
KW - Influenza vaccine
KW - Neutralizing antibodies
KW - Vaccine effectiveness
UR - http://www.scopus.com/inward/record.url?scp=85122546623&partnerID=8YFLogxK
U2 - 10.1093/cid/ciaa1352
DO - 10.1093/cid/ciaa1352
M3 - Article
C2 - 32898271
AN - SCOPUS:85122546623
SN - 1058-4838
VL - 73
SP - E4312-E4320
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
IS - 11
ER -