tetano
Editor, Senior Moderator
J Clin Invest
. 2021 Jul 1;131(13):148763.
doi: 10.1172/JCI148763.
Influenza vaccination in the elderly boosts antibodies against conserved viral proteins and egg-produced glycans
Jiwon Jung[SUP] 1 [/SUP], Sophia T Mundle[SUP] 2 [/SUP], Irina V Ustyugova[SUP] 2 [/SUP], Andrew P Horton[SUP] 3 [/SUP], Daniel R Boutz[SUP] 4 [/SUP], Svetlana Pougatcheva[SUP] 2 [/SUP], Ponraj Prabakaran[SUP] 2 [/SUP], Jonathan R McDaniel[SUP] 3 [/SUP], Gregory R King[SUP] 5 [/SUP], Daechan Park[SUP] 5 [/SUP], Maria D Person[SUP] 6 [/SUP], Congxi Ye[SUP] 4 7 [/SUP], Bing Tan[SUP] 3 [/SUP], Yuri Tanno[SUP] 3 [/SUP], Jin Eyun Kim[SUP] 1 [/SUP], Nicholas C Curtis[SUP] 7 [/SUP], Joshua DiNapoli[SUP] 2 [/SUP], Simon Delagrave[SUP] 2 [/SUP], Ted M Ross[SUP] 8 [/SUP], Gregory C Ippolito[SUP] 4 9 [/SUP], Harry Kleanthous[SUP] 2 [/SUP], Jiwon Lee[SUP] 7 [/SUP], George Georgiou[SUP] 1 3 4 5 9 [/SUP]
Affiliations
Abstract
Seasonal influenza vaccination elicits a diminished adaptive immune response in the elderly, and the mechanisms of immunosenescence are not fully understood. Using Ig-Seq, we found a marked increase with age in the prevalence of cross-reactive (CR) serum antibodies that recognize both the H1N1 (vaccine-H1) and H3N2 (vaccine-H3) components of an egg-produced split influenza vaccine. CR antibodies accounted for 73% ± 18% of the serum vaccine responses in a cohort of elderly donors, 65% ± 15% in late middle-aged donors, and only 13% ± 5% in persons under 35 years of age. The antibody response to non-HA antigens was boosted by vaccination. Recombinant expression of 19 vaccine-H1+H3 CR serum monoclonal antibodies (s-mAbs) revealed that they predominantly bound to non-HA influenza proteins. A sizable fraction of vaccine-H1+H3 CR s-mAbs recognized with high affinity the sulfated glycans, in particular sulfated type 2 N-acetyllactosamine (Galβ1-4GalNAcβ), which is found on egg-produced proteins and thus unlikely to contribute to protection against influenza infection in humans. Antibodies against sulfated glycans in egg-produced vaccine had been identified in animals but were not previously characterized in humans. Collectively, our results provide a quantitative basis for how repeated exposure to split influenza vaccine correlates with unintended focusing of serum antibody responses to non-HA antigens that may result in suboptimal immunity against influenza.
Keywords: Adaptive immunity; Infectious disease; Influenza; Vaccines.
. 2021 Jul 1;131(13):148763.
doi: 10.1172/JCI148763.
Influenza vaccination in the elderly boosts antibodies against conserved viral proteins and egg-produced glycans
Jiwon Jung[SUP] 1 [/SUP], Sophia T Mundle[SUP] 2 [/SUP], Irina V Ustyugova[SUP] 2 [/SUP], Andrew P Horton[SUP] 3 [/SUP], Daniel R Boutz[SUP] 4 [/SUP], Svetlana Pougatcheva[SUP] 2 [/SUP], Ponraj Prabakaran[SUP] 2 [/SUP], Jonathan R McDaniel[SUP] 3 [/SUP], Gregory R King[SUP] 5 [/SUP], Daechan Park[SUP] 5 [/SUP], Maria D Person[SUP] 6 [/SUP], Congxi Ye[SUP] 4 7 [/SUP], Bing Tan[SUP] 3 [/SUP], Yuri Tanno[SUP] 3 [/SUP], Jin Eyun Kim[SUP] 1 [/SUP], Nicholas C Curtis[SUP] 7 [/SUP], Joshua DiNapoli[SUP] 2 [/SUP], Simon Delagrave[SUP] 2 [/SUP], Ted M Ross[SUP] 8 [/SUP], Gregory C Ippolito[SUP] 4 9 [/SUP], Harry Kleanthous[SUP] 2 [/SUP], Jiwon Lee[SUP] 7 [/SUP], George Georgiou[SUP] 1 3 4 5 9 [/SUP]
Affiliations
- PMID: 34196304
- DOI: 10.1172/JCI148763
Abstract
Seasonal influenza vaccination elicits a diminished adaptive immune response in the elderly, and the mechanisms of immunosenescence are not fully understood. Using Ig-Seq, we found a marked increase with age in the prevalence of cross-reactive (CR) serum antibodies that recognize both the H1N1 (vaccine-H1) and H3N2 (vaccine-H3) components of an egg-produced split influenza vaccine. CR antibodies accounted for 73% ± 18% of the serum vaccine responses in a cohort of elderly donors, 65% ± 15% in late middle-aged donors, and only 13% ± 5% in persons under 35 years of age. The antibody response to non-HA antigens was boosted by vaccination. Recombinant expression of 19 vaccine-H1+H3 CR serum monoclonal antibodies (s-mAbs) revealed that they predominantly bound to non-HA influenza proteins. A sizable fraction of vaccine-H1+H3 CR s-mAbs recognized with high affinity the sulfated glycans, in particular sulfated type 2 N-acetyllactosamine (Galβ1-4GalNAcβ), which is found on egg-produced proteins and thus unlikely to contribute to protection against influenza infection in humans. Antibodies against sulfated glycans in egg-produced vaccine had been identified in animals but were not previously characterized in humans. Collectively, our results provide a quantitative basis for how repeated exposure to split influenza vaccine correlates with unintended focusing of serum antibody responses to non-HA antigens that may result in suboptimal immunity against influenza.
Keywords: Adaptive immunity; Infectious disease; Influenza; Vaccines.