Background and objectives Patients receiving hemodialysis are at high risk for both SARS-CoV-2 infection and severe COVID-19 disease. A life-saving vaccine is available, but sensitivity to vaccines is generally lower in dialysis patients. Little is yet known about antibody responses after COVID-19 vaccination in this vulnerable group. Design, setting, participants, and measurements In this prospective single-center study, we included 22 dialysis patients and 46 healthy controls from Heidelberg University Hospital between December 2020 and February 2021. We measured anti-S1 IgG with a threshold index for detection >1, neutralizing antibodies with a threshold for viral neutralization of ≥30% and antibodies against different SARS-CoV-2 fragments 17-22 days after the first and 18-22 days after the second dose of the mRNA vaccine BNT162b2. Results After the first vaccine dose, 4/22 (18%) dialysis patients compared with 43/46 (93%) healthy controls developed positive anti-S1 IgG, with a median (IQR) anti-S1 IgG index of 0.2 (0.1-0.7) compared with 9 (4-16), respectively. SARS-CoV-2 neutralizing antibodies exceeded the threshold for neutralization in 4/22 (18%) dialysis patients compared with 43/46 (93%) in healthy controls, with a median (IQR) percent inhibition of 11 (3-24) compared with 65 (49-75), respectively. After the second dose, 14/17 (82%) of dialysis patients developed neutralizing antibodies exceeding the threshold for viral neutralization and antibodies against the receptor-binding S1-domain of the spike protein, compared to 46/46 (100%) of healthy controls, respectively. The median (IQR) percent inhibition was 51 (32-86) compared to 98 (97-98) in healthy controls. Conclusions Patients receiving long-term hemodialysis show a reduced antibody response to the first and second doses of the mRNA vaccine BNT162b2. The majority (82%) develop neutralizing antibodies after the second dose, but at lower levels than healthy controls.

Bacterial RNA (bRNA) can induce cytokine production in macrophages and dendritic cells (DCs) through a previously unidentified receptor. Gene expression analysis of murine DCs showed that bRNA induced gene regulation similar to that induced by stimulation of TLR7 with R848. Although TLR7 was dispensable for cytokine induction by bRNA, TLR-associated proteins MyD88 and UNC93B were required. TLR13 is an endosomal murine TLR that has been described to interact with UNC93B with, so far, no characterized ligand. Small interfering RNA against TLR13 reduced cytokine induction by bRNA in DCs. Moreover, Chinese hamster ovary cells transfected with TLR13, but not with TLR7 or 8, could activate NF-κB in response to bRNA or Streptococcus pyogenes in an RNA-specific manner. TLR7 antagonist IRS661 could, in addition, inhibit TLR13 signaling and reduced recognition of whole Gram-positive bacteria by DCs, also in the absence of TLR7. The results identify TLR13 as a receptor for bRNA.

Despite limited data on safety and immunogenicity, heterologous prime-boost vaccination is currently recommended for individuals with ChAdOx1 nCoV-19 prime immunization in certain age groups. In this prospective, single-center study we included 166 health care workers from Heidelberg University Hospital who received either heterologous ChAdOx1 nCoV-19/BNT162b2, homologous BNT162b2 or homologous ChAdOx1 nCoV-19 vaccination between December 2020 and May 2021. We measured anti-S1 IgG, SARS-CoV-2 specific neutralizing antibodies, and antibodies against different SARS-CoV-2 fragments 0–3 days before and 19–21 days after boost vaccination. Before boost, 55/70 (79%) ChAdOx1 nCoV-19-primed compared with 44/45 (98%) BNT162b2-primed individuals showed positive anti-S1 IgG with a median (IQR) anti-S1 IgG index of 1.95 (1.05–2.99) compared to 9.38 (6.26–17.12). SARS-CoV-2 neutralizing antibodies exceeded the threshold in 24/70 (34%) of ChAdOx1 nCoV-19-primed and 43/45 (96%) of BNT162b2-primed individuals. After boosting dose, median (IQR) anti-S1 IgG index in heterologous ChAdOx1 nCoV-19/BNT162b2 vaccinees was 116.2 (61.84–170), compared to 13.09 (7.03–29.02) in homologous ChAdOx1 nCoV-19 and 145.5 (100–291.1) in homologous BNT162b2 vaccinees. All boosted vaccinees exceeded the threshold for neutralization, irrespective of their vaccination scheme. Vaccination was well-tolerated overall. We show that heterologous ChAdOx1 nCoV-19/BNT162b2 vaccination is safe and induces a strong and broad humoral response in healthy individuals.