Immune Response after the Fourth Dose of SARS-CoV-2 mRNA Vaccine Compared to Natural Infection in Three Doses’ Vaccinated Solid Organ Transplant Recipients

Abstract

Solid organ transplant recipients (SOTRs) show higher rates of COVID-19 breakthrough infection than the general population, and nowadays, vaccination is the key preventative strategy. Nonetheless, SOTRs show lower vaccine efficacy for the prevention of severe COVID-19. Moreover, the emergence of new SARS-CoV-2 variants of concern has highlighted the need to improve vaccine-induced immune responses by the administration of repeated booster doses. In this study, we analyzed the humoral and cellular responses in a cohort of 25 SOTRs, including 15 never-infected SOTRs who received the fourth dose of the mRNA vaccine and 10 SOTRs who contracted SARS-CoV-2 infection after the third dose. We analyzed the serum IgG and IgA levels through CLIA or ELISA, respectively, and the Spike-specific T cells by ELISpot assay. We report a significant increase in anti-Spike IgG and no differences in IgA secretion in both groups of patients before and after the booster dose or the natural infection. Still, we show higher IgA levels in recovered SOTRs compared to the fourth dose recipients. Conversely, we show the maintenance of a positive Spike-specific T-cell response in SOTRs who received the fourth dose, which, instead, was significantly increased in SOTRs who contracted the infection. Our results suggest that the booster, either through the fourth dose or natural infection, in vulnerable poor responder SOTRs, improves both humoral and cellular-specific immune responses against SARS-CoV-2.

mRNA-1273 boost after BNT162b2 vaccination generates comparable SARS-CoV-2-specific functional responses in naïve and COVID-19-recovered individuals

“…Based on these functional analyses, we have confirmed that responses triggered by the Spike protein from the Omicron BA.1 (B.1.1.529/BA.1) VoC are attenuated compared with its reference WT. These results go in line with the current knowledge (20, 26) and has prompted the recommendation of a second vaccine boost, in particular for patients endangered for severe COVID-19 such as patients receiving hemodialysis (25) or transplant recipients (44).…”

Immune response, phenotyping and molecular graft surveillance in kidney transplant recipients following severe acute respiratory syndrome coronavirus 2 vaccination

“…In this study, we found that post‐vaccine anti‐spike antibody responses were predominantly among participants with previous exposure to SARS‐CoV‐2. The impact of previous SARS‐CoV‐2 infection on antibody responses post‐vaccination is consistent with previous reports and highlights the need to consider alternative approaches to the standard vaccination series in kidney transplant recipients who are less likely to be responsive 19,20 . Although activated CD4 + and CD8 + T‐cell responses were observed across the cohort, further studies will be needed to determine whether these T‐cell responses were induced in an antigen‐specific manner (Figure S4).…”

“…The impact of previous SARS-CoV-2 infection on antibody responses post-vaccination is consistent with previous reports and highlights the need to consider alternative approaches to the standard vaccination series in kidney transplant recipients who are less likely to be responsive. 19,20 Although activated CD4 + and CD8 + T-cell responses were observed across the cohort, further studies will be needed to determine whether these T-cell responses were induced in an antigen-specific manner (Figure S4). Sattler et al utilized an activation-induced marker assay to monitor spike-specific CD4 + and CD8 + specific T cell responses in kidney transplant recipients 1 and 3 weeks post-second vaccination.…”

Persistence of Immune Response Elicited by Three Doses of mRNA Vaccine against SARS-CoV-2 in a Cohort of Patients with Solid Tumors: A One-Year Follow-Up

“…Although the benefit of a fourth dose in vulnerable subjects is clear, including for other categories of immunocompromised individuals, such as transplanted patients [ 32 ], the optimal boosting timing is still uncertain [ 33 ]. This issue is important to better define vaccination programs across different risk groups, not only frail patients.…”