TY - JOUR

T1 - Signs of immunosenescence correlate with poor outcome of mRNA COVID-19 vaccination in older adults

AU - Palacios-Pedrero, Miguel Ángel

AU - Jansen, Janina M.

AU - Blume, Cornelia

AU - Stanislawski, Nils

AU - Jonczyk, Rebecca

AU - Molle, Antonia

AU - Hernandez, Mariana Gonzalez

AU - Kaiser, Franziska K.

AU - Jung, Klaus

AU - Osterhaus, Albert D. M. E.

AU - Rimmelzwaan, Guus F.

AU - Saletti, Giulietta

N1 - Funding Information: This work was supported by the Alexander von Humboldt Foundation in the framework of the Alexander von Humboldt Professorship endowed by the German Federal Ministry of Education and Research (M.A.P.-P., J.M.J., A.M. G.F.R. and G.S.); RESIST cluster of excellence (EXC 2155, project no. 390874280; M.A.P.-P., A.D.M.E.O. and G.F.R.); German Research Foundation-funded VIPER program (GRK 2485; J.M.J. and F.K.K.); the European Union’s Horizon 2020 research and innovation program ISOLDA (grant no. 848166; A.D.M.E.O. and G.F.R.); and Ministry of Science and Culture of Lower Saxony, Germany (14-76103-184 CORONA-15/20; A.D.M.E.O. and M.G.H.). M.A.P.-P. was supported by the Hannover Biomedical Research School and the Center for Infection Biology. The study was financially supported by state funds from the Ministry of Economics of Lower Saxony (C.B., N.S. and R.J.). The sponsor did not exert any influence or make any recommendation as to which groups of people should be tested. The offer of testing was requested by various institutions or groups of persons themselves. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. We thank several PhD students and coworkers at the Institutes for Technical Chemistry and Microelectronic Systems (Leibniz University Hannover, Germany) for their intense work on both PCR and antibody testing, for providing blood samples after vaccination and for enabling the identification of immunized patients as well as technical and organizational support in this project. Furthermore, we thank the medical and dental students from the Medical School Hannover and Göttingen University for their support registering individuals. We thank N. Hoppe and his team for the excellent support of the study´s ethical vote and procedures with regard to data protection (Centre of Ethics and Law in the Life Sciences, Leibniz University, Hannover, Germany). The SARS-CoV-2 membrane protein peptide array (Nr-52403) was obtained through the National Institutes of Health (NIH) Biodefense and Emerging Infections Research Resources Repository (National Institute of Allergy and Infectious Diseases, NIH).

PY - 2022/10

Y1 - 2022/10

N2 - Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is effective in preventing COVID-19 hospitalization and fatal outcome. However, several studies indicated that there is reduced vaccine effectiveness among older individuals, which is correlated with their general health status 1,2. How and to what extent age-related immunological defects are responsible for the suboptimal vaccine responses observed in older individuals receiving SARS-CoV-2 messenger RNA vaccine, is unclear and not fully investigated 1,3–5. In this observational study, we investigated adaptive immune responses in adults of various ages (22–99 years old) receiving 2 doses of the BNT162b2 mRNA vaccine. Vaccine-induced Spike-specific antibody, and T and memory B cell responses decreased with increasing age. These responses positively correlated with the percentages of peripheral naïve CD4 + and CD8 + T cells and negatively with CD8 + T cells expressing signs of immunosenescence. Older adults displayed a preferred T cell response to the S2 region of the Spike protein, which is relatively conserved and a target for cross-reactive T cells induced by human ‘common cold’ coronaviruses. Memory T cell responses to influenza virus were not affected by age-related changes, nor the SARS-CoV-2-specific response induced by infection. Collectively, we identified signs of immunosenescence correlating with the outcome of vaccination against a new viral antigen to which older adults are immunologically naïve. This knowledge is important for the management of COVID-19 infections in older adults.

AB - Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is effective in preventing COVID-19 hospitalization and fatal outcome. However, several studies indicated that there is reduced vaccine effectiveness among older individuals, which is correlated with their general health status 1,2. How and to what extent age-related immunological defects are responsible for the suboptimal vaccine responses observed in older individuals receiving SARS-CoV-2 messenger RNA vaccine, is unclear and not fully investigated 1,3–5. In this observational study, we investigated adaptive immune responses in adults of various ages (22–99 years old) receiving 2 doses of the BNT162b2 mRNA vaccine. Vaccine-induced Spike-specific antibody, and T and memory B cell responses decreased with increasing age. These responses positively correlated with the percentages of peripheral naïve CD4 + and CD8 + T cells and negatively with CD8 + T cells expressing signs of immunosenescence. Older adults displayed a preferred T cell response to the S2 region of the Spike protein, which is relatively conserved and a target for cross-reactive T cells induced by human ‘common cold’ coronaviruses. Memory T cell responses to influenza virus were not affected by age-related changes, nor the SARS-CoV-2-specific response induced by infection. Collectively, we identified signs of immunosenescence correlating with the outcome of vaccination against a new viral antigen to which older adults are immunologically naïve. This knowledge is important for the management of COVID-19 infections in older adults.

UR - http://www.scopus.com/inward/record.url?scp=85140208328&partnerID=8YFLogxK

U2 - 10.1038/s43587-022-00292-y

DO - 10.1038/s43587-022-00292-y

M3 - Article

VL - 2

SP - 896

EP - 905

JO - Nature Aging

JF - Nature Aging

IS - 10

ER -