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Purpose: Preliminary studies suggest that kidney transplant recipients (KTRs) show diminished humoral responses to SARS-CoV-2 vaccination. Although reports of allograft rejection after SARS-CoV-2 vaccination have been rare, there is no recommended framework for monitoring for potential vaccine-related allograft injury. Here, we describe an approach for longitudinal assessment of immunogenicity and safety of SARS-COV-2 vaccination in KTRs. Method(s): KTRs eligible for SARS-CoV-2 vaccination were identified through medical records, beginning March 12, 2021. Baseline and weekly blood samples were collected for SARS-CoV-2 spike protein antibody titers, dd-cfDNA and gene expression profiling (GEP) for 12 weeks. Donor specific antibody (DSA) testing was performed at baseline, 2 weeks after completion of vaccine doses and at week 12. Antibody response was defined as a 10-fold increase in total binding IgG titers. Result(s): 49 KTRs were identified for analysis. Patient demographics are shown in Table 1. Ten patients (20.4%) demonstrated a spike antibody response post- vaccination. Of responders, 80% (n=8) had a history of COVID-19. The odds ratio for the association of a history of COVID-19 with vaccine response was 18.3 (95% CI 3.2, 105.0, p=0.0005). Median dd-cfDNA levels did not differ between pre- and postvaccination (0.23% versus 0.21% respectively). There was no significant difference between pre- and post-vaccination GEP scores (9.85 versus 10.4 respectively). No patients developed clinically significant DSA, eGFR decline or allograft rejection following vaccination. Conclusion(s): Quantitative antibody responses were strongly associated with a diagnosis of prior SARS-CoV-2 infection. Stability of eGFR, dd-cfDNA, GEP profiles and lack of allosensitization reinforce the safety profile of SARS-CoV-2 vaccination in KTRs. Further studies are needed to better understand immunogenicity in SARSCoV- 2 naive individuals, including whether cellular responses are protective in the absence of humoral responses.
ABSTRACT
Purpose: Correlates of protection for SARS-CoV-2 vaccines are not well-established in kidney transplant recipients(KTRs). Studies have highlighted the importance of neutralizing antibodies(Abs), however data suggests T cell responses may play a secondary role in preventing reinfection. We performed a longitudinal assessment of immunogenicity, T and B cell response in KTRs following SARS-CoV-2 vaccination. Method(s): KTRs eligible for SARS-CoV-2 vaccination from 3/12/21 were enrolled. Baseline and weekly blood samples were collected for routine lab, SARS-CoV-2 spike protein Ab titers and cellular phenotyping for 12 weeks. Ab response was defined as a 10-fold increase in total binding IgG titers. To determine if T cell responses were induced by vaccination, we considered the proportion of activated non-naive CD4+ and CD8+ T cells post-vaccination. Result(s): 49 KTRs were enrolled ( Demographics -Table 1). 10 patients (20.4%) mounted an Ab response following vaccination. A history of COVID-19 was associated with an increased likelihood of developing an Ab response (OR: 18.3, 95% CI 3.2, 105.0, p=0.0005). For non-naive CD8+ T cells, a subset co-expressing CD38+Ki67+ was induced 1 week after the 1st immunization in some SARS-CoV- 2-naiive patients (P=0.12 versus P=0.14 for SARS-CoV-2-experienced adults, Fig 1A/B). For non-naive CD4+ T cells, induction of a subset co-expressing CD38+Ki67+ was observed at 1 week after the 1st immunization for SARS-CoV-2-naive participants (P = 0.09 for SARS-CoV-2-naive, P=0.03 for SARS-CoV-2-experienced adults, Fig 1C/D). For CD8+ and CD4+ T cells, dose 2 stimulated weak induction of the CD38+Ki67+ subset in the SARS-CoV-2-naive patients only (Fig 1A-D). Conclusion(s): Quantitative Ab responses were strongly associated with prior SARS-CoV-2 infection. Activated CD4+ and CD8+ T cell responses were evident in most patients irrespective of history of COVID-19. Further studies are needed to determine whether these activated CD4+ and CD8+ T cell responses were antigenspecific or confer immunity. (Table Presented).
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[Figure: see text].
ABSTRACT
Background: Understanding if single doses of SARS-CoV-2 mRNA vaccines in SARS-CoV-2-experienced people are fully protective is a public health priority. This study measured immune responses before and after mRNA vaccine in people with or without histories of COVID-19. Methods: Specimens were collected from participants before and 6-14 days after doses 1 and 2. Humoral assays included an S1-specific Ig ELISA and a livevirus microneutralization assay (MN) vs the original SARS-CoV-2 USA-WA1/2020 strain. ELISpot assays and 36-color spectral analysis flow cytometry assessed B- and T-cell responses. Results: 32 adults received Pfizer BioNTech vaccine and 1 received Moderna vaccine. 14 had a history of COVID-19 (median age 41, 71% female, 10 with 3/20 and 2 with 12/20 illness onset, 2 asymptomatic). 19 were SARS-CoV-2-naïve (median age 39, 47% female). S1-specific IgG/A/M ASC were detected readily by ELISpot 6-14 days after dose 1 and were higher in SARS-CoV-2-experienced (median: 200) than -naïve (median: 27) subjects;after dose 2, the converse was observed (medians 53 vs 293). By flow cytometry, T cell activation was broadly observed 6-14 days after 1st vaccination, with increases in CD4+ or CD8+ T cells expressing CD38 and Ki67 (CD4: median fold-changes 1.6 for SARS-CoV-2-experienced and 1.8 for -naïve;CD8: 3.1 and 2.2). S1-specific IgG was present at baseline in experienced subjects (median: 6320), peaked at 6-14 days post-dose 1 (median: 169000), and wasn't boosted by dose 2 (panel A). In naïve participants, S1-specific IgG was not present at baseline, low at day 6-14 (median: 66), higher at day 21 (median: 27000), and boosted by dose 2 (median: 188000). Interestingly, by 6-14 days after dose 2, experienced and naïve subjects had similar S1-specific IgG titers. The MN titers followed a similar pattern (panel B): in experienced subjects, striking increases after dose 1 (median: 9860) but no boosting by dose 2;in naïve subjects, no neutralization was observed at 6-14 days, low titers were present at 21 days post-dose 1 (median: 43), with boosting after dose 2 (median: 513). Conclusion: People with a history of SARS-CoV-2 infection who received a single dose of mRNA vaccine produced binding and neutralizing antibody titers at 6-14 days that were similar to, or higher than, titers in SARS-CoV-2-naïve people who had received 2 doses. Their titers were not boosted by a second dose. These findings support a hypothesis that SARS-CoV-2-experienced people may require only a single dose of mRNA vaccine.