Discordance Between SARS-CoV-2–specific Cell-mediated and Antibody Responses Elicited by mRNA-1273 Vaccine in Kidney and Liver Transplant Recipients

Abstract

Infectious DiseaseBackground. Severe acute respiratory syndrome coronavirus 2-specific cell-mediated immunity (SARS-CoV-2-CMI) elicited by mRNA-based vaccines in solid organ transplant (SOT) recipients and its correlation with antibody responses remain poorly characterized. Methods. We included 44 (28 kidney, 14 liver, and 2 double organ) recipients who received the full series of the mRNA-1273 vaccine. SARS-CoV-2-CMI was evaluated at baseline, before the second dose, and at 2 wk after completion of vaccination by an ELISpot-based interferon-γ FluoroSpot assay using overlapping peptides covering the S1 domain. SARS-CoV-2 immunoglobulin G seroconversion and serum neutralizing activity against the spike protein were assessed at the same points by commercial ELISA and an angiotensin-converting enzyme-2/spike antibody inhibition method, respectively. Postvaccination SARS-CoV-2-CMI was compared with 28 healthcare workers who received the BNT162b2 vaccine. Results. Positive SARS-CoV-2-CMI increased from 6.8% at baseline to 23.3% after the first mRNA-1273 dose and 59.5% after the completion of vaccination (P < 0.0001). Lower rates were observed for immunoglobulin G seroconversion (2.3%, 18.6%, and 57.1%, respectively) and neutralizing activity (2.3%, 11.6%, and 31.0%). There was a modest correlation between neutralizing titers and the magnitude of SARS-CoV-2-CMI (Spearman's rho: 0.375; P = 0.015). Fifteen recipients (35.7%) mounted SARS-CoV-2-CMI without detectable neutralizing activity, whereas 3 (7.1%) did the opposite, yielding poor categorical agreement (Kappa statistic: 0.201). Rates of positive SARS-CoV-2-CMI among SOT recipients were significantly decreased compared with nontransplant controls (82.1% and 100.0% after the first dose and completion of vaccination, respectively; P < 0.0001). Kidney transplantation, the use of tacrolimus and prednisone, and the number of immunosuppressive agents were associated with lower cell-mediated responses. Results remained unchanged when 3 recipients with prevaccination SARS-CoV-2-CMI were excluded. Conclusions. Two-thirds of SOT recipients mounted SARS-CoV-2-CMI following vaccination with mRNA-1273. Notable discordance was observed between vaccine-induced cell-mediated and neutralizing humoral immunities. Future studies should determine whether these patients with incomplete responses are effectively protected.

Determinants of antibody responses to two doses of ChAdOx1 nCoV-19 or BNT162b2 and a subsequent booster dose of BNT162b2 or mRNA-1273: population-based cohort study (COVIDENCE UK)

“…We did not study cellular responses to vaccination, and these may be discordant with humoral responses. 10,27 We also studied responses at an early time point only; a high early peak in antibody titres following vaccination is not necessarily an indicator of durable response. 36 As with any observational study, we cannot exclude the possibility that some of the associations we report might be explained by residual or unmeasured confounding.…”

“…3 Existing studies investigating determinants of vaccine immunogenicity have reported that lower antibody responses following SARS-CoV-2 vaccination associate with administration of viral vector vs messenger RNA (mRNA) vaccines, older age, poorer general health, immunosuppression and shorter inter-dose intervals. [4][5][6][7][8][9][10][11] Higher postvaccination antibody titres are seen in those with evidence of SARS-CoV-2 infection before vaccination. 9,12,13 However, these studies are limited in several respects: many are conducted in specific populations such as health care workers 5,9,12,13 or in individuals with a particular demographic or clinical characteristic that may influence vaccine immunogenicity, 6,10,11 which may constrain generalisability of their results.…”

“…[4][5][6][7][8][9][10][11] Higher postvaccination antibody titres are seen in those with evidence of SARS-CoV-2 infection before vaccination. 9,12,13 However, these studies are limited in several respects: many are conducted in specific populations such as health care workers 5,9,12,13 or in individuals with a particular demographic or clinical characteristic that may influence vaccine immunogenicity, 6,10,11 which may constrain generalisability of their results.…”

“…4-11 Higher post-vaccination antibody titres are seen in those with evidence of SARS-CoV-2 infection before vaccination. 9,12,13 However, these studies are limited in several respects: many are conducted in specific populations such as health care workers 5,9,12,13 or in individuals with a particular demographic or clinical characteristic that may influence vaccine immunogenicity, 6,10,11 which may constrain generalisability of their results. Where population-based studies have been done, 4,7,8 these did not compare the effect of two doses of viral vector vs mRNA vaccines on host response; neither did they systematically ascertain participants’ pre-vaccination SARS-CoV-2 serostatus, which is an important potential confounder of associations reported.…”

Isolation of Functional SARS-CoV-2 Antigen-Specific T-Cells with Specific Viral Cytotoxic Activity for Adoptive Therapy of COVID-19

“…While the administration of mRNA vaccines has effectively reduced COVID-19-related severe disease, hospital admissions, and mortality in healthy adults [44][45][46], vaccine efficacy has not been as high in other target populations. In fact, different studies have reported lower rates of immune responses after vaccination in patients with hematologic pathologies (chronic lymphatic leukemia, multiple myeloma, lymphoma, and myeloproliferative malignancies) [47][48][49][50], as well as in solid organ transplant recipients [51][52][53][54]. In this scenario, it may be interesting to have new alternative therapies available that focus on increasing the individual immune response against the SARS-CoV-2 infection.…”