Durable immune responses after BNT162b2 vaccination in home-dwelling old adults
Lena Hansen,
Karl Albert Brokstad,
Amit Bansal,
Fan Zhou,
Geir Bredholt,
Therese Bredholt Onyango,
Helene Heitmann Sandnes,
Rebecca Elyanow,
Anders Madsen,
Mai-Chi Trieu,
Marianne Sævik,
Hanne Søyland,
Jan Stefan Olofsson,
Juha Vahokoski,
Nina Urke Ertesvåg,
Elisabeth Berg Fjelltveit,
Shahin Shafiani,
Camilla Tøndel,
Heidi Chapman,
Ian Kaplan,
Kristin G.I. Mohn,
Nina Langeland,
Rebecca Jane Cox
Affiliations
Lena Hansen
Influenza Centre, Department of Clinical Science, University of Bergen, Bergen, Norway; Corresponding authors at: Jonas Lies Vei 87, N-5021 Bergen, Norway.
Karl Albert Brokstad
Influenza Centre, Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Safety, Chemistry and Biomedical Laboratory Sciences, Western Norway University of Applied Sciences, Bergen, Norway
Amit Bansal
Influenza Centre, Department of Clinical Science, University of Bergen, Bergen, Norway
Fan Zhou
Influenza Centre, Department of Clinical Science, University of Bergen, Bergen, Norway
Geir Bredholt
Department of Clinical Science, University of Bergen, Bergen, Norway
Therese Bredholt Onyango
Influenza Centre, Department of Clinical Science, University of Bergen, Bergen, Norway
Helene Heitmann Sandnes
Department of Clinical Science, University of Bergen, Bergen, Norway
Rebecca Elyanow
Adaptive Biotechnologies, Seattle, WA, USA
Anders Madsen
Influenza Centre, Department of Clinical Science, University of Bergen, Bergen, Norway
Mai-Chi Trieu
Influenza Centre, Department of Clinical Science, University of Bergen, Bergen, Norway
Marianne Sævik
Department of Medicine, Haukeland University Hospital, Bergen, Norway
Hanne Søyland
Department of Medicine, Haukeland University Hospital, Bergen, Norway
Jan Stefan Olofsson
Influenza Centre, Department of Clinical Science, University of Bergen, Bergen, Norway
Juha Vahokoski
Influenza Centre, Department of Clinical Science, University of Bergen, Bergen, Norway
Nina Urke Ertesvåg
Influenza Centre, Department of Clinical Science, University of Bergen, Bergen, Norway
Elisabeth Berg Fjelltveit
Influenza Centre, Department of Clinical Science, University of Bergen, Bergen, Norway
Shahin Shafiani
Adaptive Biotechnologies, Seattle, WA, USA
Camilla Tøndel
Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Pediatrics, Haukeland University Hospital, Bergen, Norway; Department of Research and Innovation, Haukeland University Hospital, Bergen, Norway
Heidi Chapman
Adaptive Biotechnologies, Seattle, WA, USA
Ian Kaplan
Adaptive Biotechnologies, Seattle, WA, USA
Kristin G.I. Mohn
Influenza Centre, Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Medicine, Haukeland University Hospital, Bergen, Norway
Nina Langeland
Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Medicine, Haukeland University Hospital, Bergen, Norway; National Advisory Unit for Tropical Infectious Diseases, Haukeland University Hospital, Bergen, Norway
Rebecca Jane Cox
Influenza Centre, Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Microbiology, Haukeland University Hospital, Bergen, Norway; Corresponding authors at: Jonas Lies Vei 87, N-5021 Bergen, Norway.
Objectives: Elderly are an understudied, high-risk group vulnerable to severe COVID-19. We comprehensively analyzed the durability of humoral and cellular immune responses after BNT162b2 vaccination and SARS-CoV-2 infection in elderly and younger adults. Methods: Home-dwelling old (n = 100, median 86 years) and younger adults (n = 449, median 38 years) were vaccinated with two doses of BNT162b2 vaccine at 3-week intervals and followed for 9-months. Vaccine-induced responses were compared to home-isolated COVID-19 patients (n = 183, median 47 years). Our analysis included neutralizing antibodies, spike-specific IgG, memory B-cells, IFN-γ and IL-2 secreting T-cells and sequencing of the T-cell receptor (TCR) repertoire. Results: Spike-specific breadth and depth of the CD4+ and CD8+ TCR repertoires were significantly lower in the elderly after one and two vaccinations. Both vaccinations boosted IFN-γ and IL-2 secreting spike-specific T-cells responses, with 96 % of the elderly and 100 % of the younger adults responding after the second dose, although responses were not maintained at 9-months. In contrast, T-cell responses persisted up to 12-months in infected patients. Spike-specific memory B-cells were induced after the first dose in 87 % of the younger adults compared to 38 % of the elderly, which increased to 83 % after the second dose. Memory B-cells were maintained at 9-months post-vaccination in both vaccination groups. Neutralizing antibody titers were estimated to last for 1-year in younger adults but only 6-months in the older vaccinees. Interestingly, infected older patients (n = 15, median 75 years) had more durable neutralizing titers estimated to last 14-months, 8-months longer than the older vaccinees. Conclusions: Vaccine-induced spike-specific IgG and neutralizing antibodies were consistently lower in the older than younger vaccinees. Overall, our data provide valuable insights into the kinetics of the humoral and cellular immune response in the elderly after SARS-CoV-2 vaccination or infection, highlighting the need for two doses, which can guide future vaccine design.Clinical trials.gov; NCT04706390.
