Humoral and cellular immune correlates of protection against COVID-19 in kidney transplant recipients

Abstract

As solid organ recipients are at high risk of severe COVID-19 and respond poorly to primary SARS-CoV-2 mRNA vaccination, they have been prioritized for booster vaccination. However, an immunological correlate of protection has not been identified in this vulnerable population. We conducted a prospective monocentric cohort study of 65 kidney transplant recipients who received three doses of SARS-CoV-2 BNT162b2 mRNA vaccination. Associations between symptomatic breakthrough infection (BTI) and vaccine responses, patient demographic and clinical characteristics were explored. Symptomatic COVID-19 was diagnosed in 32% of kidney transplant recipients during a period of six months after the administration of the third vaccine dose. During this period, SARS-CoV-2 delta and omicron were the dominant variants in the general population. Univariate analyzes identified avidity of SARS-CoV-2 receptor binding domain (RBD) binding IgG, neutralizing antibodies and SARS-CoV-2 S2 domain-specific IFN-gamma responses as correlates of protection against BTI. Some demographic and clinical parameters correlated with vaccine responses, but none correlated with the risk of BTI. In multivariate analysis, the risk of BTI was best predicted by neutralizing antibody and S2-specific IFN-gamma responses, adjusting for age, graft function and mycophenolate mofetil use. In conclusion, both antibody and T cell responses predict the risk of BTI in kidney transplant recipients who received three doses of SARS-CoV-2 mRNA vaccine. T cell responses may help compensate for the suboptimal antibody response to vaccination in this vulnerable population.

Protection from successive Omicron variants with SARS-CoV-2 vaccine and monoclonal antibodies in kidney transplant recipients

“…Finally, we lack data analyzing cellular immunity. Other immune effectors, in particular T lymphocytes, could contribute toward protection in patients with limited vaccine-induced humoral immunity ( KemLin, 2022 ).…”

Third dose of BNT162b2 improves immune response in liver transplant recipients to ancestral strain but not Omicron BA.1 and XBB

“…The increase in the cross-variant antibody breadth can be extended to the Omicron XBB, as demonstrated in our study. Studies have shown that antibodies and T cell response are associated with risk against breakthrough infection and severe disease in LTRs and kidney transplant recipients (40)(41)(42). However, the diminished humoral responses against Omicron and its sublineages observed in individuals receiving multiple IS regimens can confer sufficient protection against the presently circulating Omicron variants and future SARS-CoV-2 variants remained to be determined.…”