Details

Autor(en) / Beteiligte

• Jung, Jiwon
• Mundle, Sophia T
• Ustyugova, Irina V
• Horton, Andrew P
• Boutz, Daniel R
• Pougatcheva, Svetlana
• Prabakaran, Ponraj
• McDaniel, Jonathan R
• King, Gregory R
• Park, Daechan
• Person, Maria D
• Ye, Congxi
• Tan, Bing
• Tanno, Yuri
• Kim, Jin Eyun
• Curtis, Nicholas C
• DiNapoli, Joshua
• Delagrave, Simon
• Ross, Ted M
• Ippolito, Gregory C
• Kleanthous, Harry
• Lee, Jiwon
• Georgiou, George

Titel

Influenza vaccination in the elderly boosts antibodies against conserved viral proteins and egg-produced glycans

Ist Teil von

• The Journal of clinical investigation, 2021-07, Vol.131 (13), p.1-14

Ort / Verlag

United States: American Society for Clinical Investigation

Erscheinungsjahr

2021

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.