Humoral and Cellular Immunogenicity of the BNT162b2 Messenger RNA Coronavirus Disease 2019 Vaccine in Nursing Home Residents
Jens Van Praet, Stefaan J. Vandecasteele, Anneleen De Roo, An S. De Vriese, Marijke Reynders
Abstract
To the Editor—We read with interest the communication by Capetti et al [1]. Nursing home residents are particularly vulnerable to coronavirus disease 2019 (COVID-19) as a result of advanced age, frailty, and presence of chronic medical conditions, and have been reported to account for 56% of all COVID-19–related deaths in Belgium [2]. Vaccines are known to be less immunogenic in nursing home residents, but the response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines has not been characterized in this population [3]. We therefore sought to determine the immunogenicity of the BNT162b2 messenger RNA (mRNA) COVID-19 vaccine in nursing home residents in comparison to COVID-19–naive healthcare workers 4 weeks after the first vaccine dose. One hundred consecutive residents from 2 Belgian long-term care facilities were studied after vaccination with 2 doses, administered with a 3-week interval. This study was approved by the local institutional review board, and written informed consent was obtained. We determined both humoral (antibodies against the receptor binding domain of the S1 subunit of the spike protein, chemiluminescent microparticle immunoassay [CMIA] on Architect-I System from Abbott) and cellular (QuantiFERON SARS-CoV-2 Antigen 2, Qiagen) responses, as current evidence indicates that the immunological correlate of protective immunity requires a balance between neutralizing anti-S antibodies and Th1 responses [4]. COVID-19–experienced and COVID-19–naive residents were segregated by presence (n = 36) or absence (n = 64) of antibodies against SARS-CoV-2 nucleocapsid (CMIA on Architect-I System from Abbott), based on the observations by Capetti et al [1]. Fifteen consecutive healthcare workers without spike antibodies before vaccination were used as controls. Statistical testing was performed with the Kruskal-Wallis test followed by Dunn multiple comparisons tests for continuous variables and Fisher’s exact tests for categorical variables. The nursing home residents had a mean age of 86 years (range, 56–109 years), 71% were female, and 100% were white. The median activities of daily living score according to a 6-item evaluation scale (Katz) was 17 of 24 (range, 9–24), and 20% had mild and 38% had moderate or severe cognitive impairment (based on the Mini-Mental State Examination score). Major comorbidities are available in Supplementary Table 1. Four weeks after the first vaccine dose, medians of the antibody titers were 32 226 AU/mL in COVID-19–experienced and 1762 AU/mL in COVID-19–naive residents vs 8476 AU/mL in COVID-19–naive healthcare workers (Figure 1A). Using a 1050 AU/mL cutoff, corresponding to a Plaque reduction neutralization test dilution of 1:80, an antibody response could be documented in 97% of COVID-19–experienced residents, 61% of COVID-19–naive residents, and 93% of COVID-19–naive healthcare workers (P < .001). Medians of the interferon-γ responses were 0.89 IU/mL in COVID-19–experienced and 0.13 IU/mL in COVID-19–naive residents vs 1.18 IU/mL in the COVID-19–naive healthcare workers (Figure 1B). Using a cutoff of 0.15 IU/mL, a cellular response could be documented in 97% of COVID-19–experienced residents, 48% of COVID-19–naive residents, and 87% of COVID-19–naive healthcare workers (P < .001). A combined humoral and cellular response was found in 97% of COVID-19–experienced residents, 37% of COVID-19–naive residents, and 87% of COVID-19–naive healthcare workers (Figure 1C; P < .001). A, Quantitative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike antibody titers (assessed by means of chemiluminescent microparticle immunoassay and expressed as AU/mL) in 100 nursing home residents and 15 seronegative healthcare workers 4 weeks after the first of 2 doses of BNT162b2 messenger RNA (mRNA) coronavirus disease 2019 (COVID-19). Medians with interquartile ranges are shown. B, QuantiFERON response (assessed by means of enzyme-linked immunosorbent assay and expressed as IU/mL) in 100 nursing home residents and 15 seronegative healthcare workers 4 weeks after the first of 2 doses of BNT162b2 mRNA COVID-19. Medians with interquartile ranges are shown. C, Correlation between the QuantiFERON response and quantitative SARS-CoV-2 spike antibody titers. Dotted lines correspond to the cutoffs of 0.15 IU/mL and 1050 AU/mL, respectively. Abbreviations: COVID-19, coronavirus disease 2019; IFN-γ, interferon gamma; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2. Four weeks after the first vaccine dose, the humoral and cellular immunogenicity of the BNT162b2 mRNA vaccine was suboptimal in COVID-19–naive nursing home residents in comparison to COVID-19–naive healthcare workers. Longitudinal studies are required to determine whether these differences are the result of a delayed or a quantitatively lower immune response and will be informative to tailor the optimal vaccination strategy in this vulnerable population. Supplementary materials are available at Clinical Infectious Diseases online. Consisting of data provided by the authors to benefit the reader, the posted materials are not copyedited and are the sole responsibility of the authors, so questions or comments should be addressed to the corresponding author. Acknowledgments. The authors are indebted to Ms Mirjam Demesmaecker, Ms Isabel Moyaert, Dr Lies Pottel, Ms Melissa Renders, and Ms Manon Verhulst for excellent technical and logistical assistance. Potential conflicts of interest. The authors: No potential conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.