key: cord-0823643-f3nr57vp
authors: Giménez, Estela; Albert, Eliseo; Zulaica, Joao; Torres, Ignacio; Rusu, Luciana; Rodríguez Moreno, Alicia; Burgos, Javier S; Peiró, Salvador; Salas, Dolores; Vanaclocha, Hermelinda; Limón, Ramón; Alcaraz, María Jesús; Sánchez-Payá, José; Díez-Domingo, Javier; Comas, Iñaki; Gonzáles-Candelas, Fernando; Geller, Ron; Navarro, David
title: SARS-CoV-2 adaptive immunity in nursing home residents following a third dose of the Comirnaty® COVID-19 vaccine
date: 2022-03-21
journal: Clin Infect Dis
DOI: 10.1093/cid/ciac223
sha: f5da37a9d7010d94b3c6da53fc95833c9f055dee
doc_id: 823643
cord_uid: f3nr57vp

A third Comirnaty® vaccine dose increased SARS-CoV-2-receptor binding domain antibody levels (median of 93-fold) and neutralizing antibody titers against Wuhan-Hu-1 (median, 57-fold), Beta (median, 22-fold), Delta, (median, 43-fold) and Omicron (median, 8-fold) variants, particularly in SARS-CoV-2-naïve individuals, but had a negligible impact on S-reactive T-cell immunity in nursing home residents.

Health organizations and drug regulatory agencies in Western countries recently endorsed the use of an additional dose of mRNA COVID-19 vaccines for highly vulnerable population groups, including the elderly [1] . This recommendation is strongly supported by the reduction in vaccine effectiveness a few months following a two-dose schedule against circulating SARS-CoV-2 variants of concern that has been documented in the general population [2, 3] . Vaccine-elicited adaptive immunity appears to wane more substantially and at a faster rate in elderly individuals with frailty and comorbidities compared to younger healthy controls [4] . In this context, there is limited information as to the effect of a third mRNA COVID-19 vaccine dose on SARS-CoV-2 adaptive immune responses in this population group [5] . Here, as part of the "Monitoring of antibody responses following SARS-CoV-2 vaccination in nursing homes of the Valencian Community" program launched by the Valencian Community (VC) government (COVID-19 vaccine research program -ProVaVac-) [6] we assessed SARS-CoV-2-Spike (S) targeting antibody and T-cell responses in nursing home residents after receipt of a third dose of the Comirnaty® COVID-19 vaccine.

The current observational cohort study was carried out under the epidemiological surveillance Neutralizing antibodies (NtAb) targeting the S protein were measured using a GFP-expressing vesicular stomatitis virus pseudotyped with the Wuhan-Hu-1 G614, Beta, Delta, and Omicron variants, as previously described [7] . SARS-CoV-2-S specific-IFNγ-producing CD4 + and CD8 + T-cell immunity were enumerated by whole-blood flow cytometry for intracellular cytokine staining (ICS) (BD Fastimmune, Becton Dickinson and Company Biosciences, San Jose, CA), as previously reported [6, 8] . Further details are given in the Supplementary Material, and the antibodies used are listed in Supplementary Table 2 .

Frequency comparisons for categorical variables were carried out using the Fisher exact test.

Differences between medians were compared using the Mann-Whitney U-test or the Wilcoxon test, as appropriate. Two-sided exact P-values were reported. A P-value <0.05 was considered statistically significant. The analyses were performed using SPSS version 20.0 (SPSS, Chicago, IL, USA). Figure 1) .

T-cell immunity data were obtained for 26 randomly selected residents: 17 SARS-CoV-2-naïve and 9 experienced. SARS-CoV-2-S specific, IFNγ-producing CD4 + T cells were detected in 23 and 22 residents at baseline and after 3D, respectively. In turn, SARS-CoV-2-S-specific, IFNγ-producing CD8 + T cells were detectable in 23 and 21 residents, respectively. After 3D, a slight but not statistically significant increase in CD4 + T-cell frequencies was observed in SARS-CoV-2-naïve residents, while A c c e p t e d M a n u s c r i p t 7 CD8 + T-cell frequencies decreased significantly ( Figure 1E ). In contrast, no significant differences in SARS-CoV-2-S specific, IFNγ-producing CD4 + or CD8+ T cell levels were observed SARS-CoV-2experienced individuals ( Figure 1F ). residents. This observation needs to be verified by using different platforms for T-cell immunity assessment. In addition, this finding must be interpreted with caution due to the low number of participants examined, absence of follow-up samples (peak levels could have been reached at later times after 3D sampling) and the lack of standardization of the flow cytometry assay employed.

Despite its relatively limited sample size, and lack of a control group, our study convincingly proves that receipt of a third Comirnaty® vaccine dose robustly boosts SARS-CoV-2-S specific antibody responses in elderly nursing home residents, particularly SARS-CoV-2-naïve ones. How this effect translates into protection against SARS-CoV-2 infection and COVID-19 in this population group needs

Booster or additional vaccination doses in patients vaccinated against COVID-19

Effectiveness of mRNA BNT162b2 COVID-19 vaccine up to 6 months in a large integrated health system in the USA: a retrospective cohort study

Waning Immunity after the BNT162b2 Vaccine in Israel

Long-term immunogenicity of BNT162b2 vaccination in older people and younger health-care workers

Antibody Titers Before and After a Third Dose of the SARS-CoV-2 BNT162b2 Vaccine in Adults Aged ≥60 Years

Immunological response against SARS-CoV-2 following full-dose administration of Comirnaty COVID-19 vaccine in nursing home residents

Neutralizing antibodies against SARS-CoV-2 variants of concern elicited by the Comirnaty® COVID-19 vaccine in nursing home residents

B-and T-cell immune responses elicited by the Comirnaty COVID-19 vaccine in nursing-home residents

2-receptor-binding domain (RBD) total antibody levels (in binding antibody units [BAU] per mL)

at baseline in SARS-CoV-2-naïve and experienced participants. (C) Box Whisker plots depicting Neutralizing antibody (NtAb) titers against pseudotype viruses carrying the Wuhan, Beta, Delta and Omicron SARS-CoV-2 S protein. (D) Box Whisker plots showing the NtAb titer after 3D according to participants' SARS-CoV-2 infection status. Box Whisker plots depicting SARS-CoV-2-S-specific, IFNγproducing CD4 + and CD8 + T-cell frequencies at baseline and after 3D in SARS-CoV-2-naïve (E) and experienced individuals (F)

A c c e p t e d A c c e p t e d M a n u s c r i p t 11 A c c e p t e d M a n u s c r i p t