mRNA COVID-19 Vaccine for People with Kidney Failure.

Abstract

In recent CJASN publications, we find the highly anticipated results of two studies that assess the seroresponse to the BNT162b2 mRNA vaccine (Pfizer/BioNTech) to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among patients on hemodialysis. Because patients on dialysis were excluded in the vaccine trials, this is the first information we have about our patients’ response to vaccine. Grupper et al. found detectable Spike-1 antibody 30 days after the second dose of the BNT162b2 vaccine in a high proportion of patients on dialysis, 96% (54 out of 56), which compares with 100% (80 out of 80) of healthy controls (1). Titers were, however, significantly lower in patients on dialysis. Inmultivariable analysis, the lowest quartile of serotiter was associated with advancing age and a lower prevaccination lymphocyte count. In the other report, Speer and colleagues provide a more in-depth look at the humoral response to the same vaccine among 21 patients on dialysis and 46 controls, assessing titers to the Spike-1 antigen after each of the first and second doses, components of the Spike-1 antigen, crossreactivity to SARS-CoV-1 and community-dwelling coronaviruses, and neutralizing ability (2). They found that neutralizing antibody was present in 16% of patients on dialysis versus 62% in controls after the first dose, but by the second dose, proportions were 82% and 100%, respectively. Titers of neutralizing and Spike-1 antibody were significantly higher in healthy controls, which persisted in an agematched cohort analysis. The seroresponses to components of the Spike-1 antigen and other coronaviruses varied by antigen and strain, but in general, were more robust in healthy controls. Titers were significantly lowerwitholder age inhealthy controls,whereas age was less strongly associated with titers among patients on dialysis, although patients aged ,50 years were not represented. Among the strengths of these studies, the antibody assays had high sensitivity and a low false-positive rate. The studies measured antibody to Spike-1, which contains the receptor binding domain, the primary target of neutralizing antibodies that inhibit viral replication in vitro. Speer et al. had conducted active surveillance for, and excluded, infection; accordingly, these results represent the seroresponse to vaccine. This study also assessed neutralizing ability, which is a more accurate measure of vaccine-induced protection than serotiters. The limitations are that they did not assess cell-mediated immune responses, the seroresponse in patients who were previously infected, the durability of the immune response, or infection rates (2). The main finding from these two studies is that a remarkably high proportion of our patients elicit an immune response to this vaccine, higher than has been found after hepatitis B vaccine or influenza vaccines. Although this is good news, serotiters are not clinical efficacy results. This vaccine conferred 95% protection against symptomatic SARS-CoV-2 infections in the clinical trial population (3). However, our patients elicited a less robust seroresponse than healthy controls. What are the implications? The seroresponse correlateswith immuneprotection formanypathogens, and accumulating evidence suggests this holds true for SARS-CoV-2. In vitro studies find a strong correlation of Spike-1 antibody titer with neutralizing ability and with recruitment of innate immunity and T cell–specific SARS-CoV-2 responses. Studies that predate the vaccine suggest the presence of circulating antibody confers a high level of protection from reinfection. For example, in a study of health care workers who were classified as Spike-1 antibody positive (n51265) or negative (n511,364) at time 0, and followed with PCR testing every 2 weeks, the incidence of PCR positivity was 1.09 versus 0.13 per 100 patient-days for patientswhowere Spike-1 antibody negative versus antibody positive. This is a nearly 90% reduction in reinfection in patients who were antibody positive (4). A study currently in press assessed the correlation between vaccine efficacy (expressed as log risk ratio of incidence rates for infection in the vaccine to placebo groups) and the geometric mean of the peak antibody titer 7–28 days postvaccination for the seven vaccines with phase 3 trial results and serotiter data available at the time. Serotiters were indexed to convalescent sera to enable comparison across assays. Results showed a strong correlation between vaccine efficacy and titers of neutralizing antibody (P50.79) and binding antibody (receptor binding domain or Spike-1) (P50.93) (5). There may be a threshold effect of the immune response, on the basis of the finding that neutralization, and innate cellular immune functions occurred only in individuals with receptor binding domain antibody Division of Nephrology, Tufts Medical Center, Boston, Massachusetts Division of Nephrology Transplantation Dialysis and Apheresis University Hospital of Bordeaux (CHU de Bordeaux) Bordeaux, France INSERM unit 1026 Biotis, Univ. Bordeaux, Bordeaux, France