Predictive factors of a viral neutralizing humoral response after a third dose of COVID-19 mRNA vaccine

Abstract

Kidney transplant recipients (KTRs) have reduced ability to mount adequate antibody response after two doses of the COVID‐19 mRNA vaccine. French health authorities have allowed a third booster dose (D3) for KTRs, but their response is heterogeneous and tools able to discriminate the responders are lacking. Anti‐RBD IgG titers (chemiluminescence immunoassay), spike‐specific cellular responses (IFN‐γ‐releasing assay, IGRA), and in vitro serum neutralization of the virus (the best available correlate of protection), were evaluated 7–14 days after the second dose (D2) of BNT162b2 vaccine in 93 KTRs. Among the 73 KTRs, whose serum did not neutralize SARS‐CoV‐2 in vitro after D2, 14 (19%) acquired this capacity after D3, and were considered as “responders.” Exploratory univariate analysis identified short time from transplantation and high maintenance immunosuppression as detrimental factors for the response to D3. In addition, any of the presence of anti‐RBD IgGs and/or positive IGRA after D2 was predictive of response to D3. By contrast, none of the KTRs with both a negative serology and IGRA responded to D3. In summary, routinely available bioassays performed after D2 allow identifying KTRs that will respond to a booster D3. These results pave the way for the personalization of vaccination strategy in KTRs.

Immunologic response to SARS-CoV-2 mRNA vaccination in pediatric kidney transplant recipients

“…Given the poor rates of immunologic response, a three-dose regimen for immunocompromised individuals has been implemented, and was reported to be associated with a marked improvement in immunologic response in KT recipients [ 33 – 36 ]. In a French cohort of 78 adult KT recipients, SARS-COV-2 antibodies were detected in 40% of patients following the second dose compared to 68% following the third dose [ 34 ].…”

Vaccination in patients with kidney failure: lessons from COVID-19

“…Of note, in two studies that used flow cytometry, S-protein-reactive T cells were detected in 90% and 95%, respectively 137 , 139 . Importantly, detectable levels of anti-RBD IgG antibodies and S-protein-reactive CD4 + T cells were predictive of a high response to the third primary vaccine dose 131 . By contrast, <10% of patients with failed seroconversion and negative IFNγ-release assay responded to a third dose 131 .…”

An additional dose of viral vector COVID-19 vaccine and mRNA COVID-19 vaccine in kidney transplant recipients: A randomized controlled trial (CVIM 4 study)

“… 16 In a French cohort study, lower posttransplant duration and high‐maintenance immunosuppression were found to be unfavorable predictors for seroconversion in KT recipients. 22 These parameters could be used to create a COVID‐19 immunization plan customized by individual immune status. The strategy of temporarily pausing immunosuppressant use has been proposed; however, allograft rejection is a barrier to implementing this practice, especially for those with high a immunologic risk or recent transplantation.…”

“…16 In a French cohort study, lower posttransplant duration and highmaintenance immunosuppression were found to be unfavorable predictors for seroconversion in KT recipients. 22 vaccine types as a booster dose. 17 Some of our participants experienced more pain on the injected side after receiving the mRNA vaccine compared with the viral vector vaccine.…”

“…KT recipients who were maintained on less than three immunosuppressive drugs are more likely to develop antibody responses, as are those with a longer posttransplant time 16 . In a French cohort study, lower posttransplant duration and high‐maintenance immunosuppression were found to be unfavorable predictors for seroconversion in KT recipients 22 . These parameters could be used to create a COVID‐19 immunization plan customized by individual immune status.…”