Three doses of Sars-CoV-2 mRNA vaccine in older adults result in similar antibody responses but reduced cellular cytokine responses relative to younger adults
Geir Bredholt,
Marianne Sævik,
Hanne Søyland,
Thor Ueland,
Fan Zhou,
Rishi Pathirana,
Anders Madsen,
Juha Vahokoski,
Sarah Lartey,
Bente E. Halvorsen,
Tuva B. Dahl,
Mai-Chi Trieu,
Kristin G.-I. Mohn,
Karl Albert Brokstad,
Pål Aukrust,
Camilla Tøndel,
Nina Langeland,
Bjørn Blomberg,
Rebecca Jane Cox
Affiliations
Geir Bredholt
Department of Clinical Science, University of Bergen, Bergen, Norway; Influenza Centre, Department of Clinical Science, University of Bergen, Bergen, Norway; Corresponding authors at: Department of Clinical Science, University of Bergen, Laboratory, Building (5th floor), Haukeland University Hospital, Jonas Lies Vei 87, N-5021 Bergen, Norway.
Marianne Sævik
Department of Medicine, Haukeland University Hospital, Bergen, Norway
Hanne Søyland
Department of Medicine, Haukeland University Hospital, Bergen, Norway
Thor Ueland
Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway
Fan Zhou
Influenza Centre, Department of Clinical Science, University of Bergen, Bergen, Norway
Rishi Pathirana
Influenza Centre, Department of Clinical Science, University of Bergen, Bergen, Norway
Anders Madsen
Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Microbiology, Haukeland University Hospital, Bergen, Norway
Juha Vahokoski
Influenza Centre, Department of Clinical Science, University of Bergen, Bergen, Norway
Sarah Lartey
Influenza Centre, Department of Clinical Science, University of Bergen, Bergen, Norway
Bente E. Halvorsen
Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway
Tuva B. Dahl
Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway
Mai-Chi Trieu
Influenza Centre, Department of Clinical Science, University of Bergen, Bergen, Norway
Kristin G.-I. Mohn
Influenza Centre, Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Medicine, Haukeland University Hospital, 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
Pål Aukrust
Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital, Oslo, Norway
Camilla Tøndel
Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Pediatrics, 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 Centre for Tropical Infectious Diseases, Department of Medicine, Haukeland University Hospital, Bergen, Norway
Bjørn Blomberg
Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Medicine, Haukeland University Hospital, Bergen, Norway; National Centre for Tropical Infectious Diseases, Department of Medicine, 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: Department of Clinical Science, University of Bergen, Laboratory, Building (5th floor), Haukeland University Hospital, Jonas Lies Vei 87, N-5021 Bergen, Norway.
Objectives: Booster COVID-19 vaccinations are used to protect the elderly, a group vulnerable to severe disease. We compared humoral and cellular immunity in older versus younger adults up to eight months after administering a BNT16b2 booster vaccine dose. Next, we analyzed the plasma levels of soluble T cell activation/exhaustion markers. Methods: Home-dwelling older adults (n = 68, median age 86) and younger healthcare workers (n = 35, median age 39), previously vaccinated with two doses of BNT162b2, were given a booster dose at ten months after the initial dose. Our analysis consisted of spike-specific IgG, neutralizing antibodies, memory B cells, IFN-γ and IL-2 secreting T cells and soluble T cell exhaustion/activation markers. Results: Following the initial two doses, the elderly cohort exhibited lower humoral and IFN-γ responses compared to younger adults. The booster dose increased the humoral responses in both older and younger adults. At two months after the booster dose, older and younger vaccinees had comparable levels of antibodies and the responses were maintained up to 18 months. The younger cohort elicited an increase in the cellular response, while no increase was detected in the elderly. The elderly had higher plasma levels of soluble forms of the T cell activation/exhaustion markers CD25 and TIM-3, which inversely correlated with age and T-cell cytokine responses. This suggests that these markers may be related to the observed dysfunctional cellular cytokine response in older adults. However, both elderly and younger adults who experienced breakthrough infections after booster vaccination, elicited more robust humoral and IFN-γ responses. Conclusions: The booster dose elicited neutralizing and spike-specific antibody responses in the elderly that were comparable with that of the younger cohort. However, the lack of a strong cellular cytokine response to the third dose in the elderly may explain their vulnerability to severe infection and may be a consequence of exhausted or senescent T cell responses. (https://clinicaltrials.gov/study/NCT04706390).
