Effects of active cancer treatment on safety and immunogenicity of COVID-19 mRNA-BNT162b2 vaccine: preliminary results from the prospective observational Vax-On study.
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SUBMITTER: Nelli F
PROVIDER: S-EPMC8452134 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundPreliminary analysis from the Vax-On study did not find a correlation between cancer treatment type and antibody response to COVID-19 vaccination. We carried out a secondary subgroup analysis to verify the effects of comprehensive cancer treatment classification on vaccine immunogenicity.MethodsThe Vax-On study prospectively enrolled patients who started a two-dose messenger RNA-BNT162b2 vaccine schedule from 9 March 2021 to 12 April 2021 (timepoint-1). Those on active treatment within the previous 28 days accounted for the exposed cases. Patients who had discontinued such treatment by at least 28 days or received intravesical therapy represented the control cases. Quantification of immunoglobulin G (IgG) antibodies against the receptor binding domain of the S1 subunit of the SARS-CoV-2 spike protein was carried out before the second dose (timepoint-2) and 8 weeks thereafter (timepoint-3). Seroconversion response was defined at ≥50 arbitrary units/ml IgG titer. Classification of antineoplastic agents was based on their pharmacodynamic properties.ResultsThree hundred and sixty-six patients were enrolled (86 and 260 as control and exposed cases, respectively). Univariate analysis revealed a significantly lower IgG titer after both doses of vaccine in subgroups treated with tyrosine kinase inhibitors (TKIs), multiple cytotoxic agents, alkylating agents, and topoisomerase inhibitors. At timepoint-3, seroconversion response was significantly impaired in the topoisomerase inhibitors and mechanistic target of rapamycin (mTOR) inhibitors subgroups. After multivariate testing, treatment with alkylating agents and TKIs was significantly associated with a reduced change in IgG titer at timepoint-2. Treatment with mTOR inhibitors resulted in a similar interaction at each timepoint. Cyclin-dependent kinase 4/6 inhibitor treatment was independently correlated with an incremental variation in IgG titer at timepoint-3. Specific subgroups (TKIs, antimetabolites, alkylating agents, and multiple-agent chemotherapy) predicted lack of seroconversion at timepoint-2, but their effect was not retained at timepoint-3. Eastern Cooperative Oncology Group performance status 2, immunosuppressive corticosteroid dosing, and granulocyte colony-stimulating factor use were independently linked to lower IgG titer after either dose of vaccine.ConclusionsDrugs interfering with DNA synthesis, multiple-agent cytotoxic chemotherapy, TKIs, mTOR and cyclin-dependent kinase 4/6 inhibitors differentially modulate humoral response to messenger RNA-BNT162b2 vaccine.
| S-EPMC8626231 | biostudies-literature
Project description: Not available
| S-EPMC8660134 | biostudies-literature
Project description: Not available
| S-EPMC8700280 | biostudies-literature
Project description:ObjectivesThe immunogenicity and safety of the Pfizer-BioNTech BNT162b2 mRNA vaccine in people living with human immunodeficiency virus type 1 (PLWH) are unknown. We aimed to assess the immunogenicity and safety of this vaccine in PLWH.MethodsIn this prospective open study, we enrolled 143 PLWH, aged ≥18 years, who attended our clinic and 261 immunocompetent health-care workers (HCWs). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor binding domain (RBD) IgG and neutralizing antibodies were measured. Adverse events, viral load and CD4 cell counts were monitored.ResultsAt a median of 18 days (interquartile range 14-21 days) after the second dose, anti-RBD-IgG was positive in 139/141 (98%) PLWH. Among HCWs, 258/261 (98.9%) developed anti-RBD-IgG at a median of 26 days (interquartile range 24-27 days) after the second dose. Following the second dose, immune sera neutralized SARS-CoV-2 pseudo-virus in 97% and 98% of PLWH and HCWs, respectively. Adverse events were reported in 60% of PLWH, mainly pain at the injection site, fatigue and headache. AIDS-related adverse events were not reported. Human immunodeficiency virus load increased in 3/143 (2%) patients from <40 copies/mL to ≤100 copies/mL. CD4+ T-cell count decreased from a geometric mean of 700 cells/μL (95% CI 648-757 cells/μL) to 633.8 cells/μL (95% CI 588-683 cells/μL) (p < 0.01).ConclusionsBNT162b2 mRNA vaccine appears immunogenic and safe in PLWH who are on antiretroviral therapy with unsuppressed CD4 count and suppressed viral load.
| S-EPMC8382485 | biostudies-literature
Project description:BackgroundBNT162b2, an mRNA vaccine against COVID-19, is being utilised worldwide, but immunogenicity and safety data in Chinese individuals are limited.MethodsThis phase 2, randomised, double-blind, placebo-controlled trial included healthy or medically stable individuals aged 18-85 years enrolled at two clinical sites in China. Participants were stratified by age (≤55 or >55 years) and randomly assigned (3:1) by an independent randomisation professional to receive two doses of intramuscular BNT162b2 30 μg or placebo, administered 21 days apart. Study participants, study personnel, investigators, statisticians, and the sponsor's study management team were blinded to treatment assignment. Primary immunogenicity endpoints were the geometric mean titers (GMTs) of neutralising antibodies to live severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and seroconversion rates (SCR) 1 month after the second dose. Safety assessments included reactogenicity within 14 days of vaccination, adverse events (AEs), and clinical laboratory parameters. Randomised participants who received at least one dose were included in the efficacy and safety analyses on a complete case basis (incomplete/missing data not imputed). Results up to 6 months after the second dose are reported.FindingsOverall, 959 participants (all of Han ethnicity) who were recruited between December 5th, 2020 and January 9th, 2021 received at least one injection (BNT162b2, n=720; placebo, n=239). At 1 month after the second dose, the 50% neutralising antibody GMT was 294.4 (95% CI; 281.1-308.4) in the BNT162b2 group and 5.0 (95% CI; 5.0-5.0) in the placebo group. SCRs were 99.7% (95% CI; 99.0%-100.0%) and 0% (95% CI; 0.0%-1.5%), respectively (p<0.0001 vs placebo). Although the GMT of neutralising antibodies in the BNT162b2 group was greatly reduced at 6 months after the second dose, the SCR still remained at 58.8%. BNT162b2-elicited sera neutralised SARS-CoV-2 variants of concern. T-cell responses were detected in 58/73 (79.5%) BNT162b2 recipients. Reactogenicity was mild or moderate in severity and resolved within a few days after onset. Unsolicited AEs were uncommon at 1 month following vaccine administration, and there were no vaccine-related serious AEs at 1 month or 6 months after the second dose.InterpretationBNT162b2 vaccination induced a robust immune response with acceptable tolerability in Han Chinese adults. However, follow-up duration was relatively short and COVID-19 rates were not assessed. Safety data collection is continuing until 12 months after the second dose.FundingBioNTech - sponsored the trial. Shanghai Fosun Pharmaceutical Development Inc. (Fosun Pharma) - conducted the trial, funded medical writing.Clinicaltrialsgov registration numberNCT04649021. Trial status: Completed.
| S-EPMC9472569 | biostudies-literature
Project description:Extension of the interval between vaccine doses for the BNT162b2 mRNA vaccine was introduced in the United Kingdom to accelerate population coverage with a single dose. At this time, trial data were lacking, and we addressed this in a study of United Kingdom healthcare workers. The first vaccine dose induced protection from infection from the circulating alpha (B.1.1.7) variant over several weeks. In a substudy of 589 individuals, we show that this single dose induces severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing antibody (NAb) responses and a sustained B and T cell response to the spike protein. NAb levels were higher after the extended dosing interval (6-14 weeks) compared with the conventional 3- to 4-week regimen, accompanied by enrichment of CD4+ T cells expressing interleukin-2 (IL-2). Prior SARS-CoV-2 infection amplified and accelerated the response. These data on dynamic cellular and humoral responses indicate that extension of the dosing interval is an effective immunogenic protocol.
| S-EPMC8519781 | biostudies-literature
Project description: Not available
| S-EPMC8078907 | biostudies-literature
Project description:BNT162b2 has proven to be highly effective, but there is a paucity of data regarding immunogenicity factors and comparison between response to vaccination and natural infection. This study included 871 vaccinated healthcare workers (HCW) and 181 patients with natural infection. Immunogenicity was assessed by measuring anti-SARS-CoV-2 against the RBD domain of the spike protein (anti-RBD). Samples were collected 1-2 weeks after vaccination or 15-59 days post-onset of symptoms. Post-vaccine anti-RBD concentrations were associated with age, gender, vaccination side-effects (VSE) and prior infection (Pr-CoV). Anti-RBD median levels (95%CI) were lower by 2466 (651-5583), 6228 (3254-9203) and 7651 (4479-10,823) AU/mL in 35-44, 45-54, 55-70 yrs, respectively, compared with the 18-34 yrs group. In females, the median levels were higher by 2823 (859-4787), 5024 (3122-6926) in individuals with VSE, and 9971 (5158-14,783) AU/mL in HCWs with Pr-CoV. The ratio of anti-RBD in vaccinated individuals versus those with natural infection varied from 1.0 to 19.4. The high immunogenicity of BNT162b2 is verified, although its sustainability has yet to be elucidated. The use of comparative data from natural infection serological panels, expressing the clinical heterogeneity of natural infection, may facilitate early decisions for candidate vaccines to be evaluated in clinical trials.
| S-EPMC8471735 | biostudies-literature
Project description:BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (Covid-19) have afflicted tens of millions of people in a worldwide pandemic. Safe and effective vaccines are needed urgently.MethodsIn an ongoing multinational, placebo-controlled, observer-blinded, pivotal efficacy trial, we randomly assigned persons 16 years of age or older in a 1:1 ratio to receive two doses, 21 days apart, of either placebo or the BNT162b2 vaccine candidate (30 μg per dose). BNT162b2 is a lipid nanoparticle-formulated, nucleoside-modified RNA vaccine that encodes a prefusion stabilized, membrane-anchored SARS-CoV-2 full-length spike protein. The primary end points were efficacy of the vaccine against laboratory-confirmed Covid-19 and safety.ResultsA total of 43,548 participants underwent randomization, of whom 43,448 received injections: 21,720 with BNT162b2 and 21,728 with placebo. There were 8 cases of Covid-19 with onset at least 7 days after the second dose among participants assigned to receive BNT162b2 and 162 cases among those assigned to placebo; BNT162b2 was 95% effective in preventing Covid-19 (95% credible interval, 90.3 to 97.6). Similar vaccine efficacy (generally 90 to 100%) was observed across subgroups defined by age, sex, race, ethnicity, baseline body-mass index, and the presence of coexisting conditions. Among 10 cases of severe Covid-19 with onset after the first dose, 9 occurred in placebo recipients and 1 in a BNT162b2 recipient. The safety profile of BNT162b2 was characterized by short-term, mild-to-moderate pain at the injection site, fatigue, and headache. The incidence of serious adverse events was low and was similar in the vaccine and placebo groups.ConclusionsA two-dose regimen of BNT162b2 conferred 95% protection against Covid-19 in persons 16 years of age or older. Safety over a median of 2 months was similar to that of other viral vaccines. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04368728.).
| S-EPMC7745181 | biostudies-literature
Project description:Data are scarce regarding both the safety and immunogenicity of the BNT162b2 mRNA COVID-19 vaccine in patients undergoing immune cell therapy; thus, we prospectively evaluated these two domains in patients receiving this vaccine after allogeneic hematopoietic cell transplantation (HCT; n = 66) or after CD19-based chimeric antigen receptor T cell (CART) therapy (n = 14). Overall, the vaccine was well tolerated, with mild non-hematologic vaccine-reported adverse events in a minority of the patients. Twelve percent of the patients after the first dose and 10% of the patients after the second dose developed cytopenia, and there were three cases of graft-versus-host disease exacerbation after each dose. A single case of impending graft rejection was summarized as possibly related. Evaluation of immunogenicity showed that 57% of patients after CART infusion and 75% patients after allogeneic HCT had evidence of humoral and/or cellular response to the vaccine. The Cox regression model indicated that longer time from infusion of cells, female sex, and higher CD19+ cells were associated with a positive humoral response, whereas a higher CD4+/CD8+ ratio was correlated with a positive cellular response, as confirmed by the ELISpot test. We conclude that the BNT162b2 mRNA COVID-19 vaccine has impressive immunogenicity in patients after allogeneic HCT or CART. Adverse events were mostly mild and transient, but some significant hematologic events were observed; hence, patients should be closely monitored.
| S-EPMC8242200 | biostudies-literature