A Higher Antibody Response Is Generated With a 6- to 7-Week (vs Standard) Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Vaccine Dosing Interval.
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ABSTRACT:
SUBMITTER: Grunau B
PROVIDER: S-EPMC8690265 | biostudies-literature | 2021 Nov
REPOSITORIES: biostudies-literature
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A Higher Antibody Response Is Generated With a 6- to 7-Week (vs Standard) Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Vaccine Dosing Interval.
Grunau Brian B Asamoah-Boaheng Michael M Lavoie Pascal M PM Karim Mohammad Ehsanul ME Kirkham Tracy L TL Demers Paul A PA Barakauskas Vilte V Marquez Ana Citlali AC Jassem Agatha N AN O'Brien Sheila F SF Drews Steven J SJ Haig Scott S Cheskes Sheldon S Goldfarb David M DM
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20220801 1
The optimal dosing interval for severe acute respiratory syndrome coronavirus 2 vaccines remains controversial. In this prospective study, we compared serology results of paramedics vaccinated with mRNA vaccines at the recommended short (17-28 days) vs long (42-49 days) interval. We found that a long dosing interval resulted in higher spike, receptor binding domain, and spike N terminal domain antibody concentrations. ...[more]
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Project description:ImportanceExtended-interval dosing of pembrolizumab (400 mg every 6 weeks) was approved by US Food and Drug Administration (FDA) in April 2020 as an alternative to standard-interval dosing (200 mg every 3 weeks). Extended-interval dosing may enhance access, alleviate patient and health system financial toxicity, and improve patient quality of life, particularly during the COVID-19 pandemic. Neither adoption nor effectiveness of extended interval in the US has been adequately described.ObjectiveTo describe adoption of extended-interval dosing of pembrolizumab since its FDA approval and to measure its preliminary real-world effectiveness compared with standard-interval dosing.Design, setting, and participantsThis was a retrospective cohort study that used data from the Veterans Health Administration (VHA), a US-based, nationwide single-payer health system. Participants were veterans who were prescribed single-agent pembrolizumab within the VHA between April 1, 2020, and July 1, 2021. Patients receiving combinations of pembrolizumab and cytotoxic chemotherapy or tyrosine kinase inhibitors were excluded. A subcohort of veterans with non-small cell lung cancer (NSCLC) was also identified using claims-based codes.ExposuresSingle-agent pembrolizumab at extended or standard intervals.Main outcomes and measuresThe number and proportion of single-agent pembrolizumab prescriptions that were extended compared with standard interval. Effectiveness was described in terms of time-to-treatment discontinuation (TTD) and extended- to standard-interval pembrolizumab prescriptions were compared using Cox proportional hazards regression.ResultsA total of 835 veterans (mean age [SD], 70.9 [8.7] years; 809 [96.9%] men) began single-agent pembrolizumab during the study period (all-diseases cohort), and of these, 234 (mean [SD] age, 71.6 [7.3] years; 225 [96.2%] men) had NSCLC (NSCLC cohort). Extended-interval adoption reached its steady state plateau of approximately 35% by January 2021; 65% of participants who began standard-interval single-agent pembrolizumab received only standard-interval dosing during the treatment course. In analysis consistent with the intention-to-treat principle, no differences in TTD were observed between standard- and extended-interval dosing in either the all-diseases cohort (HR, 1.00; 95% CI, 1.00-1.00) or the NSCLC cohort (HR, 1.00; 95% CI, 1.00-1.00).Conclusions and relevanceThis retrospective cohort study found that extended-interval dosing comprised a minority of single-agent pembrolizumab prescriptions despite the FDA approval and its potential health system and public health benefits. The findings support the TTD equivalence of standard- and extended-interval pembrolizumab across indications, complementing clinical pharmacology and single-arm clinical trial data in melanoma. This study provides further support for extended-interval pembrolizumab dosing.
| S-EPMC9501784 | biostudies-literature
Project description:ImportanceZoledronic acid, a third-generation aminobisphosphonate, reduces the incidence of skeletal-related events and pain in patients with bone metastases. The optimal dosing interval for zoledronic acid is uncertain.ObjectiveTo determine whether zoledronic acid administered every 12 weeks is noninferior to zoledronic acid administered every 4 weeks.Design, setting, participantsRandomized, open-label clinical trial conducted at 269 academic and community sites in the United States. Patients (n = 1822) with metastatic breast cancer, metastatic prostate cancer, or multiple myeloma who had at least 1 site of bone involvement were enrolled between May 2009 and April 2012; follow-up concluded in April 2014.InterventionsPatients were randomized to receive zoledronic acid administered intravenously every 4 weeks (n = 911) vs every 12 weeks (n = 911) for 2 years.Main outcomes and measuresThe primary end point was the proportion of patients having at least 1 skeletal-related event (defined as clinical fracture, spinal cord compression, radiation to bone, or surgery involving bone) within 2 years after randomization and a between-group absolute difference of 7% as the noninferiority margin. Secondary end points included the proportion of patients with at least 1 skeletal-related event by disease type, pain as assessed by the Brief Pain Inventory (range, 0-10; higher scores indicate worse pain), Eastern Cooperative Oncology Group performance status (range, 0-4; higher scores indicate worse disability), incidence of osteonecrosis of the jaw, kidney dysfunction, skeletal morbidity rate (mean number of skeletal-related events per year), and, in a subset of 553 patients, suppression of bone turnover (assessed by C-terminal telopeptide levels).ResultsAmong 1822 patients who were randomized (median age, 65 years; 980 [53.8%] women; 855 with breast cancer, 689 with prostate cancer, and 278 with multiple myeloma), 795 completed the study at 2 years. A total of 260 patients (29.5%) in the zoledronic acid every 4-week dosing group and 253 patients (28.6%) in the every 12-week dosing group experienced at least 1 skeletal-related event within 2 years of randomization (risk difference of -0.3% [1-sided 95% CI, -4% to ∞]; P < .001 for noninferiority). The proportions of skeletal-related events did not differ significantly between the every 4-week dosing group vs the every 12-week dosing group for patients with breast cancer, prostate cancer, or multiple myeloma. Pain scores, performance status scores, incidence of jaw osteonecrosis, and kidney dysfunction did not differ significantly between the treatment groups. Skeletal morbidity rates were numerically identical in both groups, but bone turnover was greater (C-terminal telopeptide levels were higher) among patients who received zoledronic acid every 12 weeks.Conclusions and relevanceAmong patients with bone metastases due to breast cancer, prostate cancer, or multiple myeloma, the use of zoledronic acid every 12 weeks compared with the standard dosing interval of every 4 weeks did not result in an increased risk of skeletal events over 2 years. This longer interval may be an acceptable treatment option.Trial registrationclinicaltrials.gov Identifier: NCT00869206.
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Project description:Natalizumab is approved for multiple sclerosis treatment at a dose of 300 mg every 4 weeks. Extended-interval dosing of natalizumab has been proposed as a strategy to mitigate the risk of progressive multifocal leukoencephalopathy, but the efficacy of extended-interval dosing is not established. Previous models suggesting lower efficacy when initiating natalizumab treatment with extended-interval dosing rather than every-4-week dosing are inconsistent with reports from clinical observations and real-world studies conducted in patient populations switching to extended-interval dosing after a period of receiving natalizumab every 4 weeks. Here, the efficacy of natalizumab extended-interval dosing was modeled specifically in patients switching from every-4-week dosing to extended-interval dosing. Published population pharmacokinetic/pharmacodynamic models were used to simulate the distribution of alpha-4 integrin saturations for different body weight categories and dosing intervals (every 5, 6, 7, 8, 10, or 12 weeks). Generalized estimating equations relating alpha-4 integrin saturation to probability of multiple sclerosis lesion or relapse were derived from RESTORE trial data, which included patients (n = 175) who discontinued natalizumab after being treated every 4 weeks for ≥1 year and had no relapses in the year before discontinuation. The model-based simulations described indicate that every-5-week or every-6-week dosing is likely to maintain the efficacy of natalizumab, particularly at body weights <80 kg, in patients who switch after a period of stability on every-4-week dosing. The efficacy of natalizumab decreases as dosing intervals and body weight increase. Partial model validation was achieved in that observed outcomes in an independent clinical study were similar to those predicted by the models.
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Project description:BackgroundTwo- and 3-dose BNT162b2 vaccine effectiveness (VE) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, including Delta and Omicron variants, was assessed among adolescents in Canada, where first and second doses were spaced longer than the manufacturer-specified 3-week interval.MethodsTest-negative design estimated VE against laboratory-confirmed SARS-CoV-2 infection ≥14 days after vaccination among 12-17-year-olds in Quebec and British Columbia, Canada, between 5 September 2021 and 30 April 2022 (epidemiological weeks 36-17). VE was explored by the interval between first and second doses, time since the second dose, and with a third dose.ResultsThe VE against Delta was ≥90% until at least 5 months after the second dose. The VE against Omicron decreased from about 65%-75% at 2-3 weeks to ≤50% by the third month after vaccination, restored to approximately 65% by a third dose. Although confidence intervals overlapped, VE against Omicron was about 5%-7% higher (absolute) when first and second doses were spaced ≥8 versus 3-4 weeks apart.ConclusionsIn adolescents, 2 BNT162b2 doses provided strong and sustained protection against Delta but reduced and rapidly waning VE against Omicron. A longer interval between first and second doses and a third dose marginally improved Omicron protection.
| S-EPMC10132765 | biostudies-literature
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Project description:We identified the domains of CD26 involved in the binding of Middle East respiratory syndrome coronavirus (MERS-CoV) using distinct clones of anti-CD26 monoclonal antibodies (MAbs). One clone, named 2F9, almost completely inhibited viral entry. The humanized anti-CD26 MAb YS110 also significantly inhibited infection. These findings indicate that both 2F9 and YS110 are potential therapeutic agents for MERS-CoV infection. YS110, in particular, is a good candidate for immediate testing as a therapeutic modality for MERS.
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Project description:It is unknown how the respiratory microbiome influences and is influenced by bacterial pneumonia in dogs, as culture of lung samples and not microbial sequencing guides clinical practice. While accurate identification of pathogens are essential for treatment, not all bacteria are cultivable and the impact of respiratory dysbiosis on development of pneumonia is unclear. The study purposes were to (1) characterize the lung microbiome in canine bacterial pneumonia and compare deviations in dominant microbial populations with historical healthy controls, (2) compare bacteria identified by culture vs. 16S rDNA sequencing from bronchoalveolar lavage fluid (BALF) culture-, and (3) evaluate similarities in lung and oropharyngeal (OP) microbial communities in community-acquired and secondary bacterial pneumonia. Twenty BALF samples from 15 client-owned dogs diagnosed with bacterial pneumonia were enrolled. From a subset of dogs, OP swabs were collected. Extracted DNA underwent PCR of the 16S rRNA gene. Relative abundance of operational taxonomic units (OTUs) were determined. The relative abundance of bacterial community members found in health was decreased in dogs with pneumonia. Taxa identified via culture were not always the dominant phylotype identified with sequencing. Dogs with community-acquired pneumonia were more likely to have overgrowth of a single organism suggesting loss of dominant species associated with health. Dogs with secondary bacterial pneumonia had a greater regional continuity between the upper and lower airways. Collectively, these data suggest that dysbiosis occurs in canine bacterial pneumonia, and culture-independent techniques may provide greater depth of understanding of the changes in bacterial community composition that occur in disease.
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Project description:A new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has recently emerged to cause a human pandemic. Although molecular diagnostic tests were rapidly developed, serologic assays are still lacking, yet urgently needed. Validated serologic assays are needed for contact tracing, identifying the viral reservoir, and epidemiologic studies. We developed serologic assays for detection of SARS-CoV-2 neutralizing, spike protein-specific, and nucleocapsid-specific antibodies. Using serum samples from patients with PCR-confirmed SARS-CoV-2 infections, other coronaviruses, or other respiratory pathogenic infections, we validated and tested various antigens in different in-house and commercial ELISAs. We demonstrated that most PCR-confirmed SARS-CoV-2-infected persons seroconverted by 2 weeks after disease onset. We found that commercial S1 IgG or IgA ELISAs were of lower specificity, and sensitivity varied between the 2 assays; the IgA ELISA showed higher sensitivity. Overall, the validated assays described can be instrumental for detection of SARS-CoV-2-specific antibodies for diagnostic, seroepidemiologic, and vaccine evaluation studies.
| S-EPMC7323511 | biostudies-literature
Project description:IntroductionVaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is an effective way of protecting individuals from severe coronavirus disease 2019 (COVID-19). However, immune responses to vaccination vary considerably. This study dynamically assessed the neutralizing antibody (NAb) responses to the third dose of the inactivated COVID-19 vaccine administered to people living with human immunodeficiency virus (HIV; PLWH) with different inoculation intervals.MethodsA total of 171 participants were recruited: 63 PLWH were placed in cohort 1 (with 3-month interval between the second and third doses), while 95 PLWH were placed in cohort 2 (with 5-month interval between the second and third doses); 13 individuals were enrolled as healthy controls (HCs). And risk factors associated with seroconversion failure after vaccination were identified via Cox regression analysis.ResultsAt 6 months after the third vaccination, PLWH in cohort 2 had higher NAb levels (GMC: 64.59 vs 21.99, P < 0.0001) and seroconversion rate (68.42% vs 19.05%, P < 0.0001). A weaker neutralizing activity against the SARSCoV-2 Delta variant was observed (GMT: 3.38 and 3.63, P < 0.01) relative to the wildtype strain (GMT: 13.68 and 14.83) in both cohorts. None of the participants (including HCs or PLWH) could mount a NAb response against Omicron BA.5.2. In the risk model, independent risk factors for NAb seroconversion failure were the vaccination interval (hazed ration [HR]: 0.316, P < 0.001) and lymphocyte counts (HR: 0.409, P < 0.001). Additionally, PLWH who exhibited NAb seroconversion after vaccination had fewer initial COVID-19 symptoms when infected with Omicron.DiscussionThis study demonstrated that the third vaccination elicited better NAb responses in PLWH, when a longer interval was used between vaccinations. Since post-vaccination seroconversion reduced the number of symptoms induced by Omicron, efforts to protect PLWH with risk factors for NAb seroconversion failure may be needed during future Omicron surges.Clinical trial registrationhttps://beta.clinicaltrials.gov/study/NCT05075070, identifier NCT05075070.
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