B and T Cell Responses after a Third Dose of SARS-CoV-2 Vaccine in Kidney Transplant Recipients

Abstract

Background: Accumulating evidence suggests that solid organ transplant recipients, as opposed to the general population, show strongly impaired responsiveness towards standard SARS-CoV-2 mRNA-based vaccination, demanding alternative strategies for protection of this vulnerable group. Methods: In line with recent recommendations, a third dose of either heterologous ChAdOx1 (AstraZeneca) or homologous BNT162b2 (BioNTech) was administered to 25 kidney transplant recipients (KTR) without humoral response after 2 doses of BNT162b2, followed by analysis of serological responses and vaccine-specific B- and T-cell immunity. Results: 9/25 (36%) KTR under standard immunosuppressive treatment seroconverted until day 27 after the third vaccination, while one patient developed severe COVID-19 infection immediately after vaccination. Cellular analysis seven days after the third dose showed significantly elevated frequencies of viral spike protein receptor binding domain specific B cells in humoral responders as compared to non-responders. Likewise, portions of spike-reactive CD4+ T helper cells were significantly elevated in seroconverting patients. Furthermore, overall frequencies of IL-2+, IL-4+ and polyfunctional CD4+ T cells significantly increased after the third dose, whereas memory/effector differentiation remained unaffected. Conclusions: Our data suggest that a fraction of transplant recipients benefits from triple vaccination, where seroconversion is associated with quantitative and qualitative changes of cellular immunity. At the same time, the study highlights that modified vaccination approaches for immunosuppressed patients still remain an urgent medical need.

Efficacy of covid-19 vaccines in immunocompromised patients: systematic review and meta-analysis

“… 109 110 111 112 113 In addition, 11 studies reporting seroconversion data of a third vaccine dose were included for qualitative analysis (see supplementary table 5). 43 114 115 116 117 118 119 120 121 122 123 One study was included in both meta-analysis and qualitative analysis of a third vaccine dose. 43 Five studies that met the inclusion criteria for meta-analysis were excluded because missing data could not be obtained in time from the corresponding authors.…”

“…Ten prospective observational studies and one randomised controlled trial reported data after a third dose of covid-19 vaccine. Most of the studies (8/11 studies) were on organ transplant recipients, 115 116 117 118 119 120 121 122 with one study each on patients with immune mediated inflammatory disorders, 123 haematological cancers, 114 and solid cancers. 43 Nine studies utilised only mRNA vaccines (mRNA-1273 or BNT162b2), whereas two studies 114 121 administered either BNT162b2 or AZD1222 as a third dose after two doses of BNT162b2.…”

Neutralizing Antibody Activity Against the B.1.617.2 (delta) Variant Before and After a Third BNT162b2 Vaccine Dose in Hemodialysis Patients

“…In solid organ transplant recipients, immunosuppressive drug number and type are major risk factors of seroconversion failure (34). As a significant proportion of solid organ transplant recipients still has impaired seroconversion rates even after a third mRNA vaccine dose, individualized vaccine protocols seem necessary for these vulnerable patients and vaccination prior to transplantation appears mandatory (18,(35)(36)(37)(38)(39)(40)(41)(42).…”

Insights From Early Clinical Trials Assessing Response to mRNA SARS-CoV-2 Vaccination in Immunocompromised Patients

“…Unfortunately, administration of a third dose of the vaccine was not efficient in patients on belatacept therapy (140). Importantly, the third vaccine dose increased not only Ab titers but also spike-reactive B and CD4 + T cells (141).…”