Humoral and Cellular Immune Responses of Solid Organ Transplant Patients on Belatacept to Three Doses of mRNA-Based Anti-SARS-CoV-2 Vaccine

Abstract

Background: Two doses of anti-SARS-CoV-2 mRNA-based vaccines are poorly immunogenic in solid organ transplant recipients (SOT). Methods: In total, 68 belatacept-treated SOT recipients followed at the Toulouse University Hospital were investigated. They were given three injections of the BNT162b2 mRNA COVID-19 vaccine. Their humoral response was assessed by determining anti-spike antibodies and neutralizing antibodies. The T-cell responses were assessed using an enzyme-linked immunospot assay that measured the interferon-γ produced by specific SARS-CoV-2 T-cells in a subgroup of 17 patients. Results: Only 23.5% of these patients developed a detectable anti-spike response. Moreover, the cellular and the humoral responses were well correlated. Patients with no humoral response were also without a detectable cellular response. Those belatacept-treated patients who developed an anti-SARS-CoV2 humoral response were younger, had been transplanted for longer, and had a higher lymphocyte count and a better glomerular filtration rate than those with no response. Finally, patients on tacrolimus plus belatacept produced a lower immune response. Conclusions: Belatacept-treated SOT recipients have a reduced immune response to anti-SARS-CoV-2 mRNA vaccination. The vaccine should be given quite separately from the belatacept infusion to improve immunogenicity. Studies to assess whether switching to another immunosuppressive regimen can improve the post-vaccination immune response would be useful.

A quick scoping review of the first year of vaccination against the COVID-19 pandemic: Do we need more shots or time?

“…In contrast, an increase in neutralizing antibody response induced by a booster dose against Delta [32,48,67] and Omicron [49,68] variants in the general population and immunocompromised patients has been reported by various authors. Immunocompromised patient populations include kidney transplant recipients [53][54][55][56][57][58][59][60][61]66,[68][69][70] and patients undergoing chronic hemodialysis. [51,57,63,74,76] Although >90 vaccines for COVID-19 are under clinical trials, 23 vaccines have been approved for use in different countries in 2021.…”

“…Antibody responses after third or booster dose vaccination among the general population [32,33,39,41,43–45,47–50] and among immunocompromised patients [51–76] have also been evaluated in multiple studies. The waning of immunity against different variants of SARS-CoV-2, such as Delta [16,19,22,25] and Omicron, [28,29] has been reported in several studies.…”

“…Abravanel et al, 2022 (France) [70] Prospective study among belatacept-treated solid organ transplant patients (n = 68)…”

Response of antibody titers to SARS-CoV-2 vaccination and clinical outcomes during the predominance of the Omicron variant in Colombia

“…The composite outcome of hospitalization, mechanical ventilation, and death occurred in patients with titers less than 0.8 IU/mL except in one case (IgG anti-RBD antibody titers SARS spike CoV-2 Elecsys Test, Roche, 1.48 IU/mL), which did not follow the recommendations of the transplant group on the need for timely medical attention and died 4 weeks after the onset of symptoms; these findings could indicate a poor humoral immune response to secondary vaccination among other factors secondary to pharmacological immunosuppression, mainly anti-metabolites and co-stimulation inhibitors described in other analyses. 9,10,25–29…”

Glucocorticoids selectively affect the memory T cell response to SARS-Cov2 spike in vaccinated and post-infected patients with systemic lupus erythematosus

“…The serological tests were carried out on serum and the level of IgG antibodies to SARS-Cov2 Spike mammalian cell-expressed recombinant protein was assessed by using the SARS-CoV-2 IgG II Quant assay (Abbott Laboratories, IL, USA). ELISA total values are expressed in BAU/mL, and with an assigned cutoff at 7.14 BAU/mL, as previously described [ 19 , 20 ]. The SARS-CoV-2 IgG assay (Abbott Nuc) was used to detect anti-Nuc antibodies using a threshold fixed at 1.4 [ 21 ].…”