#5520 EFFICACY OF MRNA VACCINE BNT162B2 AGAINST NOVEL SARS-COV-2 VIRUS IN END-STAGE KIDNEY DISEASE
Authors: Milo Gai , Daoud-Asfour Haneen , Karram Marian , Tchirkov Marina , Cohen Ben , Azoulay Tehila , Bershadsky Nelly Zaltzman , Slouzkey Ilana , Szwarcwort Moran , Assady Suheir 
Published: June 2023

Abstract

Background and Aims
Covid-19 pandemic affected more than 600 million people worldwide. Chronic kidney disease was shown to be a significant risk factor for disease severity. The introduction of the novel mRNA vaccines against SARS-CoV-2 prompted studies to evaluate their efficacy and safety. This study aims to assess the humoral response to the BNT162b2 vaccine, its durability, the booster effect, and breakthrough infections among end-stage renal disease patients (ESRD).

Methods
A one-year, single center, observational prospective study was conducted between 2021 and 2022. The cohort included adult dialysis patients (n = 143), kidney transplant recipients (11), and healthy controls (n = 75). Demographic and clinical data were retrieved from electronic medical records. All participants received 30 µg/dose of BNT162b2 mRNA vaccine, at 0 and 3 weeks. A third vaccine (booster) was administered at least 6 months after the first dose. SARS-CoV-2 infection was diagnosed based on PCR test of nasal and oropharyngeal swabs. Infections that occurred from January 2022 were attributed to omicron variant. Longitudinal blood samples were collected as indicated in Figure after the first vaccine dose (V1) and after the booster dose (V3). Humoral immune response was assessed by measuring serum IgG antibodies against the receptor-binding domain of the SARS-CoV-2 S1 subunit, using the ABBOTT kit. The study protocol was approved by the Institutional Review Board and was conducted in adherence to the Declaration of Helsinki.

Results
Twenty-eight weeks after two doses of vaccine, the median antibody levels were significantly lower in dialysis and transplant patients compared with healthy controls (122 AU/mL (2–4,557) and 6 AU/mL (1–217) vs 831 AU/mL (117–40,000), respectively). Furthermore, only 75% of dialysis patients developed positive antibody response (&gt;50 AU/mL) as compared to 100% in controls (see Figure 1). A significant waning of immunity was seen over time in both dialysis and healthy participants (p &lt; .0001). Four weeks after a booster dose, antibody levels surged and did not differ between dialysis and healthy participants 13,840 ± 15,126 AU/mL vs 18,080 ± 13,354 AU/mL, respectively (p = .283). Non-responder rate among dialysis patients dropped from 21% after a 2-dose vaccination to 7% after a booster dose. Lower antibody levels measured at 28-week after the first vaccination were associated with higher risk for Covid-19 infection (p = .021). Of note, all infection cases occurred in subjects with antibody levels below 1050 AU/mL. However, no association was found between antibody levels and Covid-19-omicron variant infection rate among dialysis patients and healthy controls (p = 0.650).

Conclusions
Dialysis patients had a blunted humoral immune response after two doses of BNT162b2 vaccine compared with healthy controls, which improved after a booster dose. Based on the observed omicron variant breakthrough infections, further studies are needed to improve the vaccines' efficacy against the evolving SARS-CoV-2 variants.