ABSTRACT
Background: People with HIV (PWH) older than age 55 have an enhanced risk of complications from SARS-CoV-2 infection. It is unclear whether COVID-19 vaccines with a booster are as durable in terms of immunogenicity in this cohort or whether these vaccines can destabilize HIV reservoirs. Method(s): We prospectively studied 91 PWH on cART aged 55 or over (n=91) and 23 age-matched individuals without HIV (control group, CG) who received three doses of COVID-19 vaccines (D1-D3) over 48 weeks. Participants received combinations of BNT162b2, mRNA-1273, and ChAdOx1. Of PWH, 42 were immune responders (IR), 20 were non-responders (INR), and 3 had a low-level viremia (LLV). Total and neutralizing Abs to SARS-CoV-2 spike (S) and RBD in sera and saliva, frequency of anti-RBD/NTD memory B cells (spectral flow cytometry), S-specific T cell immunity (IFN-g, IL-2 ELISpot) and HIV reservoirs in peripheral CD4+ T cells (IPDA) were measured. Result(s): No significant differences in vaccine regimens or dosing intervals were observed between PWH and CG. Vaccines elicited equally strong anti-S IgG in PWH vs CG in serum and saliva, and RBD IgG in serum. Serum Abs peaked at 4w after D3. Week 48 serum IgG in PWH vs CG were 916 vs 919 BAU/ mL for S (p=0.624) and 706 vs 752 for RBD (p=0.198), respectively. Week 48 median saliva S IgG: 48.1% AUC of the positive control in PWH vs 95.9% for CG (p=0.384). S IgA: 3.83 vs 20.5 in PWH vs CG (p=0.039). Median neutralizing titers post-D2 were significantly lower in PWH than in CG (NT50 82.9 vs 535, p< 0.001). However, after D3, at 48w, PWH had similar titers as CG: 309 vs 269 (p=0.745), mirroring an increase in RBD/NTD-specific B cells in PWH. Anti-S T cell cytokine responses were stronger in IR PWH after D2 and D3 than in CG. Week 48 S IL-2 responses: median 135 SFC/106 PBMC vs 43.8 (p< 0.001), but only 12.5 in INR (p=0.001 vs IR). COVID-19 vaccines did not affect the size of HIV reservoir in PWH (change in median frequency of intact proviruses from baseline: 95.0 vs 90.9, p=0.952), except in three LLV PWH (mean increase 93.7% at 48w). Conclusion(s): PWH aged 55 and over show diminished neutralizing Ab responses to SARS-CoV-2 with two vaccine doses which are 'rescued' after a booster. PWH have lower S-specific IgA in saliva after vaccination which may affect protection. Enhanced S-specific T cell immunity in PWH suggests Th1 imprinting from preexistent HIV infection. COVID-19 vaccines did not destabilize the HIV reservoir in most PWH but may pose potential risk in unsuppressed viremia.
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.
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BACKGROUND Little is known about the impact of immunosuppressants on COVID-19 vaccination in patients with immune-mediated inflammatory diseases (IMID). Although humoral response may be attenuated in patients using immunomodulators (IMM) and TNFinhibitors (anti-TNF), data regarding cellular response are scarce and conflicting. This study was aimed to identify immune response to COVID-19 vaccination in IMID patients. METHODS A prospective observational multicentre cohort study was conducted to examine the immunogenicity of mRNA vaccines to SARS-CoV-2 in adult IMID patients using immunosuppressive therapy (anti-TNF, IMM, anti-TNF+IMM, anti-IL12/23, anti-IL-17, anti-IL-23) or no therapy as compared to healthy controls (HC). Patient details and vaccination history were recorded. Blood samples were drawn at 3 time points: before, 3-4 weeks after first and 2 weeks after second vaccination. Humoral immune response to S and RBD proteins were assessed by ELISA. Neutralization was tested against 4 variants of SARS-CoV-2 by surrogate neutralization ELISA. Cellular immune responses were determined based on analysis of 9 secreted cytokines and cytotoxic molecules after stimulation of PBMC with S peptide pools. Response to N protein was used to assess SARS-CoV-2 exposure. RESULTS A total of 159 subjects (133 IMID patients and 26 HC) were included in this study (median age 42 years [IQR 30-53], 52% male). Of 133 IMID patients, 87 had inflammatory bowel disease, 23 psoriatic arthritis, 18 psoriasis, 11 ankylosing spondylarthritis and 4 rheumatoid arthritis. Of these, 44 used anti-TNF, 9 IMM, 18 anti-TNF+IMM, 33 anti-IL-12/23, 9 anti-IL-17, 10 anti-IL-23 therapy and 10 no therapy. All subjects received 2 doses of mRNA vaccines (2x Pfizer, 2x Moderna or mixed) between December 2020 and September 2021. The vast majority of subjects had minimal binding antibody and T cell responses to N, indicating they were COVID-19 naïve. After dose 1, anti-TNF group had lower IL-2 vs untreated IMID (p<0.01), and the anti-IL-23 group had lower IFN-g vs HC (p<0.01), though there was wide variation in responses within groups. Following dose 2, median responses between groups were mostly similar, but antibody responses were significantly lower in patients on anti-TNF as compared to HC in subjects that received two doses of Pfizer (p=0.01). Pooled data for all subjects combined show a higher response to Moderna over Pfizer in ELISA, neutralization and T cell readouts, and a lower response for those over 60 years of age after dose 2. Longer follow-up is in process to monitor the durability of these responses over time and after third dose. CONCLUSION Immune responses after 2 doses of mRNA vaccines in immunocompromised IMID patients largely reach the level of that of HC albeit antibody responses in the anti-TNF group are weaker and with wide variability between subjects within some groups
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Background: In attempts to rapidly immunize a greater proportion of the Ontario population against COVID, public health officials recommended extending the interval between vaccine doses and allowed "mixing of vaccine types". The impact of these decisions on the antibody response to the vaccine, particularly in the community dwelling elderly population is unknown. Methods: The STOPCoV study is designed to compare the IgG antibody response to spike protein and receptor binding domain (RBD) after COVID vaccination in those aged ≥ 70 years relative to a cohort aged 30-50 years. This prospective decentralized observational study is conducted remotely on a digital platform (www.stopcov.ca). Participants signed an e-consent, completed questionnaires and will submit dried blood spot (DBS) specimens 6-8 times over 48 weeks after the second vaccine dose. DBS samples were analyzed for IgG antibodies to spike and RBD by an in-house ELISA. We report here the ratio-normalized levels of anti-spike and anti-RBD IgG antibodies prior to and at 2 weeks after the second vaccine with comparisons between age groups. Linear regression models were used to determine the effect of age on the ratio normalized RBD antibody levels 2 weeks post second dose of vaccine after adjusting for potential confounders determined a priori. Results: 1286 persons enrolled between May 17 and July 31, 2021. 1194 participants (853 > 70 years;341 aged 30-50) completed at least one study related task. 761 (64.1%) are female. Most received an mRNA vaccine, with 863 (74%) receiving the same vaccine brand, and 196 (17%) receiving mixed brands over 2 doses. Two weeks after the second vaccine dose, the median interquartile rangeanti-spike antibody level was 0.76 [0.45, 1.16] for those ≥70 compared to 1.3 [0.98, 1.56] for those 30-50 (p<0.001). The median anti-RBD antibody levels were 0.28 [0.15, 0.53] and 0.66 [0.41, 1.08] (p<0.001) for the older and younger cohorts respectively. After adjusting for gender, cardiovascular disease, cancer, diabetes, transplant or immune suppression, body mass index, vaccine brand, and time between doses, participants ≥70 had lower levels of anti-RBD antibodies at 2 weeks after 2nd dose (β=-0.14, 95% confidence interval-0.19,-0.08, p<0.0001). Conclusion: High antibody levels against COVID-19 are attainable after 2 doses of mRNA vaccines. Levels were higher with Moderna than Pfizer. Delay of the second dose to 4 months or mixing of brands had minimal impact on the antibody level but levels are lower in the elderly.
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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.
ABSTRACT
Background/Case Studies: Multiple assays to detect SARS-COV-2 antibodies are available but no gold standard exists. Due to many factors including waning antibodies and differences in test designs, discordance between SARS-CoV-2 serology assays is common. Given these limitations we used multiple assays and methodological approaches to estimate SARS-COV-2 seroprevalence during the first COVID-19 wave in Canada. Study Design/Methods: This serial cross-sectional study was conducted using residual plasma from healthy blood donors between April-September 2020. Qualitative (Table Presented) assessment of SARS-CoV-2 IgG antibodies was based on four assays: Abbott Architect SARS-Cov-2 IgG assay (target nucleocapsid) (Abbott-NP) and three in-house IgG ELISA assays (target spike glycoprotein (Spike), spike receptor binding domain (RBD), and nucleocapsid (NP)) based on thresholds set by the manufacture or 3-standarddeviations from the negative mean. We compared seroprevalence rates by multiple composite reference standards (CRS) and by a series of Bayesian Latent Class Models (BLCM) (using uninformative, weakly and informative priors). Using the BLCM we estimated assay characteristics, bimonthly to evaluate changes over time. Results/Findings: In total, 8999 blood samples were tested. The Abbott-NP assay consistently estimated seroprevalence to be lower than the ELISA-based assays. A priori, choosing a combination of 2 assays resulted in a range of seroprevalence estimates that ranged from 0.2% to 0.5% in April to 0.4% to 1.5% in September. From 16 possible diagnostic phenotypes, 13 were observed, only 33 samples (0.4%) were positive by all four assays. BLCM with non-informative priors provided the best model fit and predicted seroprevalence increased from 0.7% (95% CrI;0.6, 0.8%) in April/May to 1.0% (0.8, 1.1%) in June/ July to 1.5% (1.3, 1.8) in August/September. Assay characteristics varied considerably over time. Overall RBD had the highest sensitivity 82.2% (69.3, 92.9%) with a specificity of 99.6% (99.4, 99.7%). In contrast the sensitivity of the Abbott-NP assay was the lowest and waned from 63.2% (41.4, 83.1%) in April/May to 33.9% (19.7, 53.1%) by August/September. Conclusions: Regardless of the analytical method we found at the end of the first COVID-19 wave, SARSCoV- 2 seroprevalence among a healthy population of blood donors was low (<2%). While the sensitivity of all assays waned, the rates did vary. We found significant limitations to using a single assay to estimate SARSCoV- 2 seroprevalence in a low prevalence setting, such as healthy Canadian blood donors during the first wave of the COVID-19 pandemic.