ABSTRACT
Background: Due to waning humoral immunity, a third COVID-19 vaccine dose is recommended but there is a lack of evidence regarding whether there is benefit to homologous versus heterologous mRNA vaccination. Method(s): This was a multi-centre parallel group randomized controlled trial in Toronto, Ontario from September 30, 2021 to May 13, 2022 which enrolled participants with stage 3B-5 chronic kidney disease with prior homologous mRNA two dose vaccination. Overall 273 participants were randomized 1:1 to either 30mug BNT162b2 (n=137) or 100 mug mRNA-1273 (n=136) third dose stratified by initial vaccine type. Neutralizing antibodies against the B.1.1.529 (Omicron) variant of concern as well as binding SARS-CoV-2 IgG antibodies to the spike protein, receptor binding domain, and nucleocapsid protein were measured. Result(s): Participants had a median age of 67 years, 94% were on dialysis, 3% had prior COVID-19, and 59% had received BNT162b2 for initial two dose vaccination. Prior to the third vaccine dose, detectable Omicron neutralizing antibodies were present in 2% with BNT162b2 and 54% with mRNA-1273 two dose vaccination. At 1 month post third dose, among those with baseline BNT162b2, Omicron-specific neutralizing antibodies were detectable in 84% with third dose BNT162b2 in comparison to 83% with third dose mRNA-1273 (p=0.70). In those with baseline mRNA-1273, 100% receiving third dose mRNA-1273 had Omicron-specific neutralizing antibodies in comparison to 96% with third dose BNT162b2 (p=0.75). During the study period, 9.3% of participants (n=25) contracted COVID-19 and two died from COVID-19 with no difference in infection based on vaccine type (p=0.26). Conclusion(s): In this randomized controlled trial of third dose COVID-19 vaccination, both homologous and heterologous vaccination elicited robust SARS-CoV-2 neutralizing antibody response. (Figure Presented).
ABSTRACT
Background: Kidney transplant recipients (KTR) have a diminished response to SARS-CoV-2 vaccination in comparison to immunocompetent individuals. Deeper understanding of the antibody response in KTRs following third-dose vaccination would enable identification of those who remain unprotected against Omicron and require additional treatment strategies. Method(s): We profiled antibody responses in KTRs pre-and at one and three months post-third-dose SARS-CoV2 mRNA-based vaccine. Anti-spike and anti-RBD IgG levels were determined by ELISA. Neutralization against wild-type, Beta, Delta and Omicron (BA.1) variants was determined using a SARS-CoV-2 spike pseudotyped lentivirus assay. Result(s): 44 KTRs were analysed at 1 and 3 months (n=26) post-third-dose. At one month, the proportion of participants with a robust antibody response had increased significantly from baseline, but Omicron-specific neutralizing antibodies were detected in just 45% of KTRs. Median anti-spike and anti-RBD antibody levels declined at 3 months, but the proportion of KTRs with a robust antibody response was unchanged. 38.5% KTRs maintained Omicron-specific neutralization at 3 months. No clinical variables were significantly associated with detectable Omicron neutralizing antibodies, but anti-RBD titres appeared to identify those with Omicron-specific neutralizing capacity. Conclusion(s): Over 50% of KTRs lack an Omicron-specific neutralization response 1 month following a third mRNA-vaccine dose. Among responders, binding and neutralizing antibody responses were well preserved at 3 months. Anti-RBD antibody titres may be a useful identifier of patients with detectable Omicron neutralizing antibody response.
ABSTRACT
Background: The impact of immunosuppressants on COVID-19 vaccination response and durability in patients with immune-mediated infammatory diseases (IMID) is yet to be fully characterized. Humoral response may be attenuated in these patients especially those on B cell depleting therapy and higher doses of corticosteroids, but data regarding other immunosuppressants are scarce. Objectives: We aimed to investigate antibody and T cell responses and durability to SARS-CoV-2 mRNA vaccines (BNT162b and/or mRNA 1273) in IMID patients on immunomodulatory maintenance therapy other than B-cell depleting therapy and corticosteroids. Methods: This prospective observational cohort study examined the immuno-genicity of SARS-CoV-2 mRNA vaccines in adult patients with IMIDs (psoriatic arthritis, psoriasis, infammatory bowel disease and rheumatoid arthritis) with or without maintenance immunosuppressive therapies (anti-TNF, methotrexate/azathioprine [MTX/AZA], anti-TNF + MTX/AZA, anti IL12/23, anti-IL-17, anti-IL23) compared to healthy controls. Automated ELISA for IgGs to spike trimer, spike receptor binding domain (RBD) and the nucleocapsid (NP) and T-cell release of 9 cytokines (IFNg, IL2, IL4, IL17A, TNF) and cytotoxic molecules (sFasL, GzmA, GzmB, Perforinin) in cell culture supernatants following stimulation with spike or NP peptide arrays were conducted at 4 time points: T1=pre vaccination, T2=me-dian 26 days after dose 1, T3=median 16 days after dose 2 and T4=median 106 days after dose 2. Neutralization assays against four SARS-CoV-2 variants (wild type, delta, beta and gamma) were conducted at T3. Results: We followed 150 subjects: 26 healthy controls and 124 IMID patients: 9 untreated, 44 on anti-TNF, 16 on anti-TNF with MTX/AZA, 10 on anti-IL23, 28 on anti-IL12/23, 9 on anti-IL17, 8 on MTX/AZA (Table 1). Most patients mounted antibody and T cell responses with increases from dose 1 to dose 2 (100% sero-conversion at T3) and some decline by T4, with variability within groups. Antibody levels and neutralization efficacy was lower in anti-TNFgroups (anti-TNF, anti-TNF + MTX/AZA) compared to controls and waned by T4 (Figure 1). T cell responses were not consistently different between groups. Pooled data showed a higher antibody response to mRNA-1273 compared to BNT162b. Conclusion: Following 2 doses of mRNA vaccination there is 100% seroconver-sion in IMID patients on maintenance therapy. Antibody levels and neutralization efficacy in anti-TNF group are lower than controls, and wane substantially by 3 months after dose 2. These fndings highlight the need for third dose in patients undergoing treatment with anti-TNF therapy and continued monitoring of immunity in these patient groups, taking into consideration newer variants and additional vaccine doses.
ABSTRACT
Background: Hemodialysis (HD) patients have high mortality from COVID-19 and immunity following vaccination remains uncertain. This study evaluated SARS-CoV-2 antibody response in HD patients following BNT162b2 COVID-19 vaccination compared to health care workers (HCW) and convalescent serum. Methods: This single centre observational cohort study enrolled 142 HD patients and 35 HCW receiving the BNT162b2 vaccine. SARS-CoV-2 IgG antibodies to the spike protein (anti-spike), receptor binding domain (anti-RBD), and nucleocapsid protein (anti-NP) were measured in 66 HD patients receiving one vaccine dose, 76 HD patients receiving two vaccine doses, and 35 HCW receiving two vaccine doses. Results: In HD patients receiving a single BNT162b2 dose, seroconversion occurred in 53/66 (80%) for anti-spike and 35/66 (55%) for anti-RBD by 28 days post dose, but only 15/66 (23%) and 4/66 (6%), respectively attained a robust response defined as reaching the median level of anti-spike and anti-RBD in convalescent serum. In patients receiving two doses of BNT162b2 vaccine, seroconversion occurred in 69/72 (96%) for anti-spike and 63/72 (88%) for anti-RBD by 2 weeks following the second dose while 52/72 (72%) and 43/72 (60%) reached median convalescent serum levels of anti-spike and anti-RBD. In HCW, 35/35 (100%) exceeded median levels of anti-spike and anti-RBD in convalescent serum 2-4 weeks post second dose. Conclusions: This study found poor immunogenicity 28 days following a single dose of BNT162b2 vaccine in HD patients, supporting adherence to recommended vaccination schedules, and avoiding delay of the second dose in this population.