Impaired humoral responses to COVID-19 vaccination in patients with lymphoma receiving B-cell-directed therapies.
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ABSTRACT:
SUBMITTER: Ghione P
PROVIDER: S-EPMC8245303 | biostudies-literature | 2021 Sep
REPOSITORIES: biostudies-literature
Publications
Impaired humoral responses to COVID-19 vaccination in patients with lymphoma receiving B-cell-directed therapies.
Ghione Paola P Gu Juan J JJ Attwood Kristopher K Torka Pallawi P Goel Shipra S Sundaram Suchitra S Mavis Cory C Johnson Michael M Thomas Roshneke R McWhite Kenneth K Darrall Andrea A DeMarco Joseph J Kostrewa Jessica J Mohr Alice A Rivas Leah L Neiders Mirdza M Suresh Lakshmanan L Segal Brahm H BH Griffiths Elizabeth A EA Ramsperger Vince V Shen Long L Hernandez-Ilizaliturri Francisco J FJ
Blood 20210901 9
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Project description:Humoral responses to COVID-19 vaccines in people living with HIV (PLWH) remain incompletely understood. We measured circulating antibodies against the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein, ACE2 displacement and live viral neutralization activities one month following the first and second COVID-19 vaccine doses in 100 adult PLWH and 152 controls. All PLWH were receiving suppressive antiretroviral therapy, with median CD4+ T-cell counts of 710 (IQR 525-935) cells/mm 3 . Nadir CD4+ T-cell counts ranged as low as <10 (median 280; IQR 120-490) cells/mm 3 . After adjustment for sociodemographic, health and vaccine-related variables, HIV infection was significantly associated with 0.2 log 10 lower anti-RBD antibody concentrations (p=0.03) and ∼11% lower ACE2 displacement activity (p=0.02), but not lower viral neutralization (p=0.1) after one vaccine dose. Following two doses however, HIV was no longer significantly associated with the magnitude of any response measured. Rather, older age, a higher burden of chronic health conditions, and having received two ChAdOx1 doses (versus a heterologous or dual mRNA vaccine regimen) were independently associated with lower responses. After two vaccine doses, no significant correlation was observed between the most recent or nadir CD4+ T-cell counts and vaccine responses in PLWH. These results suggest that PLWH with well-controlled viral loads on antiretroviral therapy and CD4+ T-cell counts in a healthy range will generally not require a third COVID-19 vaccine dose as part of their initial immunization series, though other factors such as older age, co-morbidities, vaccine regimen type, and durability of vaccine responses will influence when this group may benefit from additional doses. Further studies of PLWH who are not receiving antiretroviral treatment and/or who have low CD4+ T-cell counts are needed.
| S-EPMC8528088 | biostudies-literature
Project description:Humoral responses to COVID-19 vaccines in people living with HIV (PLWH) remain incompletely characterized. We measured circulating antibodies against the SARS-CoV-2 spike protein receptor-binding domain (RBD), ACE2 displacement and viral neutralization activities one month following the first and second COVID-19 vaccine doses, and again 3 months following the second dose, in 100 adult PLWH and 152 controls. All PLWH were receiving suppressive antiretroviral therapy, with median CD4+ T-cell counts of 710 (IQR 525-935) cells/mm3, though nadir CD4+ T-cell counts ranged as low as <10 cells/mm3. After adjustment for sociodemographic, health and vaccine-related variables, HIV infection was associated with lower anti-RBD antibody concentrations and ACE2 displacement activity after one vaccine dose. Following two doses however, HIV was not significantly associated with the magnitude of any humoral response after multivariable adjustment. Rather, older age, a higher burden of chronic health conditions, and dual ChAdOx1 vaccination were associated with lower responses after two vaccine doses. No significant correlation was observed between recent or nadir CD4+ T-cell counts and responses to two vaccine doses in PLWH. These results indicate that PLWH with well-controlled viral loads and CD4+ T-cell counts in a healthy range generally mount strong initial humoral responses to dual COVID-19 vaccination. Factors including age, co-morbidities, vaccine brand, response durability and the rise of new SARS-CoV-2 variants will influence when PLWH will benefit from additional doses. Further studies of PLWH who are not receiving antiretroviral treatment or who have low CD4+ T-cell counts are needed, as are longer-term assessments of response durability.
| S-EPMC8885829 | biostudies-literature
Project description:Age-associated B cells (ABC) accumulate with age and in individuals with different immunological disorders, including cancer patients treated with immune checkpoint blockade and those with inborn errors of immunity. Here, we investigate whether ABCs from different conditions are similar and how they impact the longitudinal level of the COVID-19 vaccine response. Single-cell RNA sequencing indicates that ABCs with distinct aetiologies have common transcriptional profiles and can be categorised according to their expression of immune genes, such as the autoimmune regulator (AIRE). Furthermore, higher baseline ABC frequency correlates with decreased levels of antigen-specific memory B cells and reduced neutralising capacity against SARS-CoV-2. ABCs express high levels of the inhibitory FcγRIIB receptor and are distinctive in their ability to bind immune complexes, which could contribute to diminish vaccine responses either directly, or indirectly via enhanced clearance of immune complexed-antigen. Expansion of ABCs may, therefore, serve as a biomarker identifying individuals at risk of suboptimal responses to vaccination.
| S-EPMC10299999 | biostudies-literature
Project description:BackgroundWhether human T-lymphotropic virus type 1 (HTLV-1) carriers can develop sufficient humoral immunity after coronavirus disease 2019 (COVID-19) vaccination is unknown.MethodsTo investigate humoral immunity after COVID-19 vaccination in HTLV-1 carriers, a multicenter, prospective observational cohort study was conducted at five institutions in southwestern Japan, an endemic area for HTLV-1. HTLV-1 carriers and HTLV-1-negative controls were enrolled for this study from January to December 2022. During this period, the third dose of the COVID-19 vaccine was actively administered. HTLV-1 carriers were enrolled during outpatient visits, while HTLV-1-negative controls included health care workers and patients treated by participating institutions for diabetes, hypertension, or dyslipidemia. The main outcome was the effect of HTLV-1 infection on the plasma anti-COVID-19 spike IgG (IgG-S) titers after the third dose, assessed by multivariate linear regression with other clinical factors.ResultsWe analyzed 181 cases (90 HTLV-1 carriers, 91 HTLV-1-negative controls) after receiving the third dose. HTLV-1 carriers were older (median age 67.0 vs. 45.0 years, p < 0.001) and more frequently had diabetes, hypertension, or dyslipidemia than did HTLV-1-negative controls (60.0% vs. 27.5%, p < 0.001). After the third dose, the IgG-S titers decreased over time in both carriers and controls. Multivariate linear regression in the entire cohort showed that time since the third dose, age, and HTLV-1 infection negatively influenced IgG-S titers. After adjusting for confounders such as age, or presence of diabetes, hypertension, or dyslipidemia between carriers and controls using the overlap weighting propensity score method, and performing weighted regression analysis in the entire cohort, both time since the third dose and HTLV-1 infection negatively influenced IgG-S titers.ConclusionsThe humoral immunity after the third vaccination dose is impaired in HTLV-1 carriers; thus, customized vaccination schedules may be necessary for them.
| S-EPMC10792913 | biostudies-literature
Project description:ObjectiveTo identify which factors influence humoral response to coronavirus disease 2019 (COVID-19) vaccination in rituximab (RTX)-treated patients.MethodsThis was an observational, prospective, usual care study including consecutive patients with inflammatory rheumatic diseases in maintenance therapy with RTX. All patients received a two-dose regimen COVID-19 vaccination. Serum IgG antibody levels against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike proteins were measured at the time of the new RTX infusion.ResultsFrom the recruited patients, 16/45 (36%) produced antibodies reaching the assay cut-off value of 15 AU/ml and 29/45 (64%) had a negative serology. Within RTX-treated patients, 25 (56%) had undetectable B cells. Negative serology was associated with undetectable B cells (24/25 vs 5/20, P < 0.001). Moreover, SARS-CoV-2 spike antibodies correlated with CD19 counts (r = 0.86, P < 0.001). The effect of RTX and MTX was additive in terms of seroconversion rates (23% vs 50% in patients receiving RTX in monotherapy, P = 0.12) and SARS-CoV-2 spike antibody levels [3.80 (95% CI 3.80, 7.50) vs 75 (95% CI 3.8, 353) AU/ml in patients receiving RTX in monotherapy; P = 0.025]. Multivariate analyses including demographics, disease characteristics, gammaglobulin levels, RTX and other therapies used, CD19 counts, and the time between the last RTX infusion and vaccination identified detectable B cells as the only variable independently associated with seropositivity [odds ratio 35.2 (95% CI 3.59, 344.20)].ConclusionsB cell depletion is the main independent contributing factor of antibody response to SARS-CoV-2 vaccination in RTX-treated patients. Monitoring CD19 may be of interest to identify the most appropriate period to perform vaccination.
| S-EPMC8689920 | biostudies-literature
Project description:Background and objectivesPatients receiving hemodialysis are at high risk for both severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severe coronavirus disease 2019. A lifesaving vaccine is available, but sensitivity to vaccines is generally lower in patients on dialysis. Little is yet known about antibody responses after coronavirus disease 2019 (COVID-19) vaccination in this vulnerable group.Design, setting, participants, and measurementsIn this prospective single-center study, we included 22 patients on dialysis 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 greater than one, neutralizing antibodies with a threshold for viral neutralization of ≥30%, and antibodies against different SARS-CoV2 fragments 17-22 days after the first dose and 18-22 days after the second dose of the mRNA vaccine BNT162b2.ResultsAfter the first vaccine dose, four of 22 (18%) patients on dialysis compared with 43 of 46 (93%) healthy controls developed positive anti-S1 IgG, with a median anti-S1 IgG index of 0.2 (interquartile range, 0.1-0.7) compared with nine (interquartile range, 4-16), respectively. SARS-CoV2 neutralizing antibodies exceeded the threshold for neutralization in four of 22 (18%) patients on dialysis compared with 43 of 46 (93%) healthy controls, with a median percent inhibition of 11 (interquartile range, 3-24) compared with 65 (interquartile range, 49-75), respectively. After the second dose, 14 of 17 (82%) patients on dialysis developed neutralizing antibodies exceeding the threshold for viral neutralization and antibodies against the receptor binding S1 domain of the spike protein, compared with 46 of 46 (100%) healthy controls, respectively. The median percent inhibition was 51 (interquartile range, 32-86) compared with 98 (interquartile range, 97-98) in healthy controls.ConclusionsPatients 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.
| S-EPMC8425619 | biostudies-literature
Project description: Not available
| S-EPMC8294866 | biostudies-literature
Project description:The ChAdOx1 nCoV-19 (AZD1222) vaccine is one of the most commonly delivered SARS-CoV-2 vaccines worldwide; however, few clinical studies have investigated its immunogenicity in dialysis patients. We prospectively enrolled 123 patients on maintenance hemodialysis at a medical center in Taiwan. All patients were infection-naive, had received two doses of the AZD1222 vaccine, and were monitored for 7 months. The primary outcomes were anti-SARS-CoV-2 receptor-binding domain (RBD) antibody concentrations before and after each dose and 5 months after the second dose and neutralization capacity against ancestral SARS-CoV-2, delta, and omicron variants. The anti-SARS-CoV-2 RBD antibody titers significantly increased with time following vaccination, with a peak at 1 month after the second dose (median titer, 498.8 U/mL; interquartile range, 162.5 to 1,050 U/mL), and a 4.7-fold decrease at 5 months. At 1 month after the second dose, 84.6, 83.7, and 1.6% of the participants had neutralizing antibodies against the ancestral virus, delta variant, and omicron variant, respectively, measured by a commercial surrogate neutralization assay. The geometric mean 50% pseudovirus neutralization titers for the ancestral virus, delta variant, and omicron variant were 639.1, 264.2, and 24.7, respectively. The anti-RBD antibody titers correlated well with neutralization capacity against the ancestral virus and delta variant. Transferrin saturation and C-reactive protein were associated with neutralization against the ancestral virus and delta variant. Although two doses of the AZD1222 vaccine initially elicited high anti-RBD antibody titers and neutralization against the ancestral virus and delta variant in hemodialysis patients, neutralizing antibodies against omicron variant were rarely detected, and the anti-RBD and neutralization antibodies waned over time. Additional/booster vaccinations are warranted in this population. IMPORTANCE Patients with kidney failure have worse immune response following vaccination compared to general population, but few clinical studies have investigated immunogenicity of ChAdOx1 nCoV-19 (AZD1222) vaccination in hemodialysis patients. Here, we showed two doses of AZD1222 vaccines lead to high seroconversion rate of anti-SARS-CoV-2 receptor-binding domain (RBD) antibodies, and more than 80% patients acquired neutralizing antibodies against ancestral virus and delta variant. However, seldom did they obtain neutralizing antibodies against the omicron variant. The geometric mean 50% pseudovirus neutralization titer against the ancestral virus was 25.9-fold higher than that against the omicron variant. Also, there was a substantial decay in anti-RBD titers with time. Our findings provided evidence supporting that more protective measures, including additional/booster vaccinations, is warranted in these patients during the current COVID-19 pandemic.
| S-EPMC10100369 | biostudies-literature
Project description:Interim immunogenicity and efficacy data for the Ad26.COV2.S vaccine for COVID-19 have recently been reported 1-3 . We describe here the 8-month durability of humoral and cellular immune responses in 20 individuals who received one or two doses of 5Ã-10 10 vp or 10 11 vp Ad26.COV2.S and in 5 participants who received placebo 2 . We evaluated antibody and T cell responses on day 239, which was 8 months after the single-shot vaccine regimen (N=10) or 6 months after the two-shot vaccine regimen (N=10), although the present study was not powered to compare these regimens 3 . We also report neutralizing antibody responses against the parental SARS-CoV-2 WA1/2020 strain as well as against the SARS-CoV-2 variants D614G, B.1.1.7 (alpha), B.1.617.1 (kappa), B.1.617.2 (delta), P.1 (gamma), B.1.429 (epsilon), and B.1.351 (beta).
| S-EPMC8282116 | biostudies-literature