Boosters Restore SARS‑CoV‑2 Immunity in Kidney Transplant Recipients

In the RECOVAC study, investigators compared kidney transplant recipients (KTRs) who seroconverted after primary vaccination with those who seroconverted only after additional booster dosing, using immune readouts collected 28 days after vaccination.

The authors report that, at this day-28 assessment, booster responders generally had humoral and cellular responses that were broadly comparable to those in primary responders, alongside several qualitative distinctions between groups. Findings are presented across antibody, memory B cell, and T cell platforms measured at the same post-vaccination timepoint.

For the in-depth immunological analyses, the article describes 80 KTRs evenly distributed between primary responders (n=40) and booster responders (n=40). Seropositivity for SARS-CoV-2 S1-specific IgG was defined as at least 10 BAU/mL, and sampling for the primary comparison was performed 28 days after priming or booster vaccination. Participants were selected from two Dutch multicenter RECOVAC studies and, per the reported inclusion framework, were clinically stable, at least 1 year post-transplantation, had no rejection episodes in the preceding year, and had no history of COVID-19. The immune comparisons are presented within this selected cohort of clinically stable kidney transplant recipients.

For humoral immunity, S1-specific IgG binding antibodies to ancestral SARS-CoV-2 increased significantly within both groups (p<0.001) and were not significantly different between primary and booster responders at day 28, as measured by a validated fluorescent bead-based multiplex immunoassay. Functional antibody assessments at 28 days included neutralization via plaque reduction neutralization testing (PRNT) and Fc-mediated measures reported as antibody-dependent cellular phagocytosis, cytotoxicity, and complement deposition; the authors report no significant between-group differences across these functionalities at the same timepoint. For Omicron BA.1, the article notes that a between-group difference was driven by a subset of responders within the booster group, described as showing stronger BA.1 neutralization than primary responders. Overall, the authors describe day-28 humoral readouts in booster responders as largely aligned with those in primary responders.

Memory B cell profiling is presented as one of the clearer distinctions between groups at day 28. SARS-CoV-2–specific memory B cells were quantified by B cell ELISpot and expressed as spots per 106 peripheral blood mononuclear cells, with a stated lower limit of detection of 10 spots per 106 cells. In these analyses, the authors report that booster responders had an expanded SARS-CoV-2–specific memory B cell pool compared with primary responders. When integrating immune compartments, the article also describes stronger correlations between cellular and humoral parameters in booster responders than in primary responders and reports a principal component analysis suggesting more refined network integration in booster responders across measured immune features. Taken together, the report highlights memory B cell expansion as a distinguishing feature in booster responders at 28 days.

Cellular immunity was assessed using IFN-γ and IL-21 ELISpot assays alongside spectral flow cytometry to identify activation-induced marker (AIM)+ SARS-CoV-2–specific T cell populations. The authors report that frequencies of AIM+ CD4 T cells (identified by CD134 and CD154 co-expression) and AIM+ CD8 T cells (identified by CD69 and CD137) did not differ between primary and booster responders at 28 days, with stimulation increasing AIM+ frequencies relative to unstimulated conditions.

For cytokine-producing memory T cells, both groups showed increased IL-21 responses by day 28, while the article reports that primary responders had higher IL-21 ELISpot counts at day 28 despite booster responders having higher baseline IL-21. Phenotypically, the authors describe three main CD4 AIM+ clusters (including a Treg-like cluster) and report that the distribution of these clusters differed between groups, including a higher proportion of a CD27+CD28+ memory cluster among primary responders. In unstimulated phenotyping, booster responders are described as having higher proportions of CD8 TEMRA cells (42% vs 34%) and a higher proportion of CD8-expressing γδ T cells, with CMV seropositivity reported as similar between groups (62% in each).

The article’s overall summary emphasizes broadly similar day-28 cellular responses with select phenotypic distinctions between primary and booster responders.

Key Takeaways:

• The authors report that, at 28 days post-vaccination, booster responders and primary responders showed broadly comparable humoral and cellular immune responses across the measured platforms.
• The authors describe an expanded SARS-CoV-2–specific memory B cell pool in booster responders and note that stronger Omicron BA.1 neutralization was driven by a subset within the booster group.
• The authors frame these comparisons within a selected cohort of clinically stable KTRs (≥1 year post-transplant; no rejection in the preceding year) and describe the enrollment/sampling approach as limiting assessment of rare adverse events.