scholarly journals Persistence of immunity and impact of a third (booster) dose of an inactivated SARS-CoV-2 vaccine, BBV152; a phase 2, double-blind, randomised controlled trial

2022 ◽  
Author(s):  
Krishna Mohan Vadrevu ◽  
Brunda Ganneru ◽  
Siddharth Reddy ◽  
Harsh Jogdand ◽  
Raju Dugyala ◽  
...  
Keyword(s):  
Placebo Group ◽  
Booster Dose ◽  
Natural Infection ◽  
Geometric Mean ◽  
Booster Vaccination ◽  
Secondary Outcome ◽  
Effector Memory ◽  
Cell Mediated Immunity ◽  
Phase 2 ◽  
Neutralising Antibodies

Background: Neutralising antibody responses to SARS-CoV-2 vaccines have been reported to decline within 6 months of vaccination, particularly against Variants of Concern (VOC). We assessed the immunogenicity and safety of a booster dose of BBV152 administered 6 months after the second of a two-dose primary vaccination series. Methods: In an ongoing phase 2 trial (ClinicalTrials.gov: NCT04471519) the protocol was amended after six months to re-consent and randomise 184 previously vaccinated participants to receive a third dose of vaccine or placebo on Day 215. The primary outcome was to measure neutralising antibody titres by plaque-reduction neutralisation test (PRNT50) four weeks after the booster; safety as serious adverse events (SAE) was the key secondary outcome. Findings: Four weeks after a second BBV152 vaccination geometric mean titres (GMTs) of neutralising antibodies were 197.0 PRNT50 (95% CI: 155.6,249.4); this level declined to 23.9 PRNT50 (14.0,40.6) six months later, with a seroconversion rate of 75.4% (95% CI: 68.4,81.6). Four weeks after booster vaccination the GMT increased on Day 243 to 746.6 PRNT50 (514.9,1081) compared with 100.7 PRNT50 (43.6,232.6) in the placebo group. Corresponding seroconversion rates were 98.7% (92.8,99.9) and 79.8% (69.6,87.8). Increased titres in the placebo group were attributed to natural infection as the study was conducted during the second wave of COVID-19 in India. PRNT50 titres against the SARS-CoV-2 variants increased Alpha (32.6 fold), Beta (161.0 fold), Delta (264.7 fold), and Delta plus (174.2 fold) after the booster vaccination. We found that vaccine induces both memory B and T cells with a distinct AIM+ specific CD4+T central and effector memory phenotype, including CD8+ TEMRA phenotype. Reactogenicity after vaccine and placebo was minimal and comparable, and no SAEs were reported. Interpretation: Six months after a two dose BBV152 vaccination series cell mediated immunity and neutralising antibodies to both homologous (D614G) and heterologous strains (Alpha, Beta, Delta and Delta plus) persisted above baseline, although the magnitude of the responses had declined. Neutralising antibodies against homologous and heterologous SARS-CoV-2 variants increased 19 to 97 fold after a third vaccination. Booster BBV152 vaccination is safe and may be necessary to ensure persistent immunity to prevent breakthrough infections.

scholarly journals Modelling the impact of extended vaccination strategies on the epidemiology of pertussis

2011 ◽  
Vol 140 (8) ◽  
pp. 1503-1514 ◽  
Author(s):  
M. H. ROZENBAUM ◽  
R. De VRIES ◽  
H. H. LE ◽  
M. J. POSTMA
Keyword(s):  
Booster Dose ◽  
Deterministic Model ◽  
Natural Infection ◽  
Age Groups ◽  
Vaccination Strategy ◽  
Booster Vaccination ◽  
Sensitivity Analyses ◽  
Wide Range ◽  
Age Structured ◽  
The Impact

SUMMARYThe aim of this study was to investigate the optimal pertussis booster vaccination strategy for The Netherlands. A realistic age-structured deterministic model was designed. Assuming a steady-state situation and correcting for underreporting, the model was calibrated using notification data from the period 1996–2000. Several sensitivity analyses were performed to explore the impact of different assumptions for parameters surrounded by uncertainty (e.g. duration of protection after natural infection, underreporting factors, and transmission probabilities). The optimal age of an additional booster dose is in the range of 10–15 years, and implementation of this booster dose will reduce both symptomatic and asymptomatic infections, although the incidence of symptomatic infections in older age groups will increase. The impact of the different assumptions used in the model was in general limited. We conclude that over a wide range of assumptions, an additional booster dose can reduce the incidence of pertussis in the population.

scholarly journals Persistence and gender differences in protection against severe fever with thrombocytopaenia syndrome virus with natural infection: a 4-year follow-up and mathematical prediction study

2019 ◽  
Vol 147 ◽  
Author(s):  
R. Qi ◽  
Y.T. Huang ◽  
X.J. Yu
Keyword(s):  
Infectious Disease ◽  
Gender Differences ◽  
Natural Infection ◽  
Geometric Mean ◽  
Case Fatality ◽  
Immune Protection ◽  
Neutralising Antibodies ◽  
And Gender ◽  
Severe Fever

SummarySevere fever with thrombocytopaenia syndrome (SFTS) is an emerging infectious disease discovered in 2010 and has a case fatality as high as 30%. We intended to study the immune protection conferred by SFTS with natural infection. We collected and analysed 4-year follow-up data to study the characteristics of neutralising antibodies against SFTS virus (SFTSV). The 50% plaque reduction neutralisation test was used for the detection of neutralising antibodies against SFTSV. Geometric mean titres (GMTs) and proportions of patients with a protective titre were analysed, and the persistence of protection was predicted. The titre of antibodies declined yearly in the 4-year study period. Approximately 3 months after infection, the GMT was 143 (95% confidence interval (CI): 89–231), and 100% of patients had a protective titre. In the fourth year, the GMT declined to 53 (95% CI: 37–76), and 95% of patients had a protective titre. The titre was higher in females than in males. On average, the protection offered by neutralising antibodies against SFTSV could last as long as 9 years. The durations of protection were different for different initial titres. The characteristics of neutralising antibodies can be used as a reference for the vaccination doses and schedules of forthcoming vaccines.

scholarly journals 4. MenACWY-TT Long-Term Antibody Persistence Following Adolescent Vaccination and Evaluation of a Booster Dose: A Review of Clinical Data

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S24-S24
Author(s):  
Paula Peyrani ◽  
Chris Webber ◽  
Cindy Burman ◽  
Paul Balmer ◽  
John L Perez
Keyword(s):  
Immune Responses ◽  
Conjugate Vaccine ◽  
Booster Dose ◽  
Geometric Mean ◽  
Booster Vaccination ◽  
Primary Vaccination ◽  
The United States ◽  
The European Union ◽  
Adolescent Vaccination

Abstract Background A peak in meningococcal carriage and invasive meningococcal disease (IMD) occurs during adolescence and young adulthood. In the United States, preventive vaccination with a quadrivalent meningococcal (MenACWY) conjugate vaccine is recommended at age 11–12 years, with a booster dose given at age 16 years. MenACWY-TT (Nimenrix®), a MenACWY tetanus toxoid conjugate vaccine, was first licensed in 2012 and is available in the European Union and 50 other countries. Immune responses to other MenACWY conjugate vaccines decline over several years following vaccination. Here, we review 2 recent studies evaluating the long-term persistence of MenACWY-TT immune responses in adolescents as well as safety and immunogenicity of a booster dose given 10 years after primary vaccination. Methods Both studies (ClinicalTrials.gov NCT01934140, NCT03189745) were extensions of phase 2 or 3 studies of subjects 11–17 years of age given a single dose of MenACWY-TT or MenACWY polysaccharide vaccine (MenACWY-PS). Immune responses through 10 years after primary vaccination and after a Year 10 MenACWY-TT booster dose were measured by serum bactericidal antibody assays using baby rabbit complement (rSBA). Specific endpoints included percentages of subjects with rSBA titers ≥1:8 and ≥1:128 and geometric mean titers (GMTs). Booster dose safety and tolerability were also evaluated. Results In both studies, the percentages of subjects with rSBA titers ≥1:8 through 10 years postvaccination were generally higher or similar among MenACWY-TT (69.3%–91.2% at Year 10; n=137–163) compared with MenACWY-PS (24.4%–88.9%; n=45–53) recipients for all 4 serogroups (Figure); similar results were observed for GMTs (146.0–446.9 vs 12.9–191.0 at Year 10). One month after a MenACWY-TT booster dose, 97.7%–100% of subjects across groups had titers ≥1:8 (Figure), and GMTs were markedly higher than prebooster values. No new safety signals were identified following the booster dose. Figure 1. Subjects in each of the 2 studies with rSBA titers ≥1:8 before and at 1 month, 5 years, and 10 years after primary vaccination with MenACWY-TT or MenACWY-PS at 11–17 years of age and 1 month after booster vaccination with MenACWY-TT at 10 years following primary vaccination. Conclusion Functional antibodies for all 4 serogroups persisted through 10 years after MenACWY-TT adolescent vaccination, suggesting that this vaccine may help prevent IMD throughout the lengthy risk period in this group. A MenACWY-TT booster dose may further extend protection regardless of the primary vaccine received. Funded by Pfizer. Disclosures Paula Peyrani, MD, Pfizer Inc (Employee, Shareholder) Chris Webber, MD, Pfizer Inc (Employee, Shareholder) Cindy Burman, PharmD, Pfizer Inc (Employee, Shareholder) Paul Balmer, PhD, Pfizer Inc (Employee, Shareholder) John L. Perez, MD, MA, Pfizer Inc (Employee, Shareholder)

scholarly journals Factors Influencing Persistence of Diphtheria Immunity and Immune Response to a Booster Dose in Healthy Slovak Adults

Vaccines ◽  
2019 ◽  
Vol 7 (4) ◽  
pp. 139
Author(s):  
Petráš ◽  
Oleár ◽  
Molitorisová ◽  
Dáňová ◽  
Čelko ◽  
...  
Keyword(s):  
Booster Dose ◽  
Geometric Mean ◽  
Booster Vaccination ◽  
Childhood Vaccination ◽  
Seroprotection Rate ◽  
Post Vaccination ◽  
Factors Influencing ◽  
Antibody Levels ◽  
Mean Concentration

We assessed the long-term persistence of humoral immunity against diphtheria in adults with childhood vaccination and the immunogenicity of a booster dose considering demographic, behavioural and vaccinating factors. We conducted a trial in 200 healthy Slovak adults aged 24–65 years, immunised against diphtheria in childhood and against tetanus at regular 10–15 year intervals, and receiving a dose of a tetanus-diphtheria toxoid vaccine. The response was determined by ELISA antibody concentrations of paired sera before and at 4 weeks post-vaccination. A seroprotection rate of 21% (95% confidence interval, CI 15.6–27.3%) was found in adults up to 59 years since the last vaccination with seroprotective levels of antibodies against diphtheria ≥0.1 IU/mL and a geometric mean concentration of 0.05 IU/mL. Conversely, seropositive levels ≥0.01 IU/mL were observed in 98% of adults (95% CI 95–99.5%). Booster-induced seroprotection was achieved in 78% of adults (95% CI 71.6–83.5%) clearly depending on pre-booster antibody levels correlating with age and time since the last vaccination. Moreover, only 54.2% of smokers and 53.3% of patients on statins exhibited seroprotection. Booster vaccination against diphtheria was unable to confer seroprotection in all recipients of only childhood vaccination.

scholarly journals Detection of IFNγ-Secreting CD4+ and CD8+ Memory T Cells in COVID-19 Convalescents after Stimulation of Peripheral Blood Mononuclear Cells with Live SARS-CoV-2

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1490
Author(s):  
Victoria Matyushenko ◽  
Irina Isakova-Sivak ◽  
Igor Kudryavtsev ◽  
Arina Goshina ◽  
Anna Chistyakova ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Memory T Cells ◽  
Natural Infection ◽  
Intracellular Cytokine Staining ◽  
T Cell Responses ◽  
Effector Memory ◽  
Memory T Cell ◽  
Cell Responses ◽  
Stimulation Of

Background: New coronavirus SARS-CoV-2, a causative agent of the COVID-19 pandemic, has been circulating among humans since November 2019. Multiple studies have assessed the qualitative and quantitative characteristics of virus-specific immunity in COVID-19 convalescents, however, some aspects of the development of memory T-cell responses after natural SARS-CoV-2 infection remain uncovered. Methods: In most of published studies T-cell immunity to the new coronavirus is assessed using peptides corresponding to SARS-CoV-1 or SARS-CoV-2 T-cell epitopes, or with peptide pools covering various parts of the viral proteins. Here, we determined the level of CD4+ and CD8+ memory T-cell responses in COVID-19 convalescents by stimulating PBMCs collected 1 to 6 months after recovery with sucrose gradient-purified live SARS-CoV-2. IFNγ production by the central and effector memory helper and cytotoxic T cells was assessed by intracellular cytokine staining assay and flow cytometry. Results: Stimulation of PBMCs with live SARS-CoV-2 revealed IFNγ-producing T-helper effector memory cells with CD4+CD45RA−CCR7− phenotype, which persisted in circulation for up to 6 month after COVID-19. In contrast, SARS-CoV-2-specific IFNγ-secreting cytotoxic effector memory T cells were found at significant levels only shortly after the disease, but rapidly decreased over time. Conclusion: The stimulation of immune cells with live SARS-CoV-2 revealed a rapid decline in the pool of effector memory CD8+, but not CD4+, T cells after recovery from COVID-19. These data provide additional information on the development and persistence of cellular immune responses after natural infection, and can inform further development of T cell-based SARS-CoV-2 vaccines.

scholarly journals Efficacy and Safety of Divaza for the Correction of Oxidative Disturbances in Patients with Cerebral Atherosclerosis: A Randomized Controlled Trial

2021 ◽  
pp. 1-11
Author(s):  
Nataliia U. Lashch ◽  
Pavel R. Kamchatnov ◽  
Tatiana N. Fedorova ◽  
Olga A. Muzychuk ◽  
Kristina K. Khacheva ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Placebo Group ◽  
Study Design ◽  
Therapeutic Option ◽  
Controlled Trial ◽  
Prospective Trial ◽  
Secondary Outcome ◽  
Secondary Outcome Measure ◽  
Cerebral Atherosclerosis ◽  
Endogenous Antioxidant

<b><i>Objective:</i></b> The objective of this study was to determine if Divaza, a drug with nootropic and antioxidant effects, was safe and effective for the correction of oxidative disturbances and to stabilize cognitive impairment in patients with cerebral atherosclerosis. <b><i>Study Design:</i></b> The study design consisted of a 12-week multicenter, randomized, double-blind, placebo-controlled, prospective trial in parallel groups. <b><i>Setting:</i></b> The setting in which the study was conducted comprised 10 clinical centers across the Russian Federation. <b><i>Interventions:</i></b> Patients were randomized into 2 groups and instructed to take either 2 tablets of the study drug or a placebo 3 times per day in conjunction with basic therapy. <b><i>Outcomes:</i></b> The primary outcome was a change in the average endogenous antioxidant potential after the completion of the study. The blood indicators of the oxidative stress (OS) were analyzed at the baseline and then after 12 weeks of therapy using iron-induced chemiluminescence analysis. The Montreal cognitive assessment test was used as a secondary outcome measure to evaluate cognitive impairment at the end of the study. <b><i>Results:</i></b> 124 outpatients with a mean age of 60.7 ± 7.6 years were enrolled and randomly assigned to receive Divaza (<i>n</i> = 65) or a placebo (<i>n</i> = 59). An improvement of cognitive function was observed in all patients of the Divaza group at the end of the treatment; this was significantly better than the placebo group (100 [100] vs. 89.5 [89.1]%, respectively, <i>p</i> = 0.0272 [<i>p</i> = 0.0128]). The administration of Divaza restored the activity of the endogenous antioxidant system. The change in the average level of lipoprotein resistance to oxidation after 12 weeks of therapy, compared to the baseline, was significantly higher in the Divaza group (14.8 ± 14.7 [14.8 ± 14.7] seconds latent period vs. 6.4 ± 16.9 [6.9 ± 16.7] seconds in the placebo group (<i>p</i> = 0.007 [<i>p</i> = 0.0107]). <b><i>Conclusions:</i></b> Divaza is a safe and effective therapeutic option for attenuating OS and recovery of cognitive impairment in patients with cerebral atherosclerosis.

scholarly journals Phase 1 and Phase 2 Studies of Salmonella enterica Serovar Paratyphi A O-Specific Polysaccharide-Tetanus Toxoid Conjugates in Adults, Teenagers, and 2- to 4-Year-Old Children in Vietnam

2000 ◽  
Vol 68 (3) ◽  
pp. 1529-1534 ◽  
Author(s):  
Edward Y. Konadu ◽  
Feng-Ying C. Lin ◽  
Vô Anh Hó ◽  
Nguyen Thi Thanh Thuy ◽  
Phan Van Bay ◽  
...  
Keyword(s):  
Side Effects ◽  
Bactericidal Activity ◽  
Tetanus Toxoid ◽  
Salmonella Enterica ◽  
Phase 1 ◽  
Geometric Mean ◽  
Age Groups ◽  
Significant Rise ◽  
Phase 2 ◽  
Specific Polysaccharide

ABSTRACT Salmonella enterica serovar Paratyphi A O-specific polysaccharide (O-SP) was activated with 1-cyano-4-dimethylaminopyridinium tetrafluoroborate (CDAP) and bound to tetanus toxoid (TT) with adipic acid dihydrazide as a linker (SPA-TT1) or directly (SPA-TT2). In mice, these two conjugates elicited high levels of immunoglobulin G (IgG) anti-lipopolysaccharide (LPS) in serum with bactericidal activity (E. Konadu, J. Shiloach, D. A. Bryla, J. B. Robbins, and S. C. Szu, Infect. Immun. 64:2709–2715, 1996). The safety and immunogenicity of the two conjugates were then evaluated sequentially in Vietnamese adults, teenagers, and 2- to 4-year-old children. None of the vaccinees experienced significant side effects, and all had preexisting LPS antibodies. At 4 weeks after injection, there were significant increases of the geometric mean IgG and IgM anti-LPS levels in the adults and teenagers: both conjugates elicited a greater than fourfold rise in the IgG anti-LPS level in serum in ≥80% of the volunteers. SPA-TT2 elicited slightly higher, though not statistically significantly, levels of IgG anti-LPS than did SPA-TT1 in these age groups. Accordingly, only SPA-TT2 was evaluated in the 2- to 4-year-old children. On a random basis, one or two injections were administered 6 weeks apart to the children. No significant side effects were observed, and the levels of preexisting anti-LPS in serum were similar in children of all ages. A significant rise in the IgG anti-LPS titer was elicited by the first injection (P = 0.0001); a second injection did not elicit a booster response. Representative sera from all groups had bactericidal activity that could be adsorbed by S. enterica serovar Paratyphi A LPS.

Measles Immunity After Revaccination: Results in Children Vaccinated Before 10 Months of Age

PEDIATRICS ◽  
1982 ◽  
Vol 69 (3) ◽  
pp. 332-335
Author(s):  
Calvin C. Linnemann ◽  
Mark S. Dine ◽  
Gary A. Roselle ◽  
P. Anne Askey
Keyword(s):  
Measles Virus ◽  
Geometric Mean ◽  
Lymphocyte Transformation ◽  
First Year ◽  
Cell Mediated Immunity ◽  
Measles Vaccine ◽  
Pediatric Practice ◽  
Antibody Titers ◽  
Measles Vaccination ◽  
First Year Of Life

Measles immunity was studied in children in a private pediatric practice who had been revaccinated because they had received their primary measles vaccination before 1 year of age. Antibody was measured in 72 of these children who had received the first injection of live measles virus vaccine at &lt;10 months of age, and the second at &gt;1 year of age. Of the 72 children, 29 (40%) had no detectable antibody and the geometric mean titer for the group was approximately 1:4. Of the children with low antibody titers, 15 were given a third injection of measles vaccine and five (33%) still did not respond. Cell- mediated immunity as indicated by lymphocyte transformation to measles antigen was measured in 11 of the children. Five (45%) had responses to measles antigen, but the responses did not correlate with the presence or absence of antibody. This study confirms the observation that revaccination is unsuccessful in many children who received measles vaccine in the first year of life, and shows that even a third injection of vaccine may fail to produce a significant antibody response.

Effect of the Modified Surgeon Assisted Bilateral Transversus Abdominis Plane Block on Time Required for First Analgesic Dose after Cesarean Section under Spinal Anesthesia: Randomized placebo-control

2021 ◽  
Vol 4 (3) ◽  
pp. 01-05
Author(s):  
Ahmed Mamdouh
Keyword(s):  
Placebo Group ◽  
Cesarean Section ◽  
Spinal Anesthesia ◽  
Interquartile Range ◽  
Transversus Abdominis ◽  
Secondary Outcome ◽  
Control Group ◽  
Placebo Control ◽  
Study Group ◽  
Tap Block

Background: The transverses abdominis plane block (TAP block) is one of the widely used regional analgesic techniques in cesarean section. There are different variations of the procedure. The aim of the present study was to evaluate the analgesic effect of the modified surgeon assisted bilateral TAP block in patients undergoing cesarean section Patients&Methods: Sixty patients undergoing cesarean section under spinal anesthesia were randomized into two groups to receive either TAP block with 40 ml of bupivacaine 0.25%(study group) or 40 ml normal saline as placebo after obtaining informed consent. All patients will receive intravenous diclofencac75mg every 12 hrs postoperatively. Postoperatively, there was an assessment every 2hrs during the first 24hrs by the visual analogue pain scale (VAPS). Time to the first analgesic request will be measured as primary outcome and all patients will receive opioid on demand or VAPS > 4 with 25mg pethidine intramuscularly. Moreover, total opioid requirement in 24hrs will be measured as secondary outcome along with postoperative complications as nausea, vomiting and abdominal distention. Complications related to the TAP procedure will be also assessed. Results: The median (interquartile range) time to the first analgesic request in the first 24hrs postoperatively was significantly shorter in the placebo group compared to the study group; 4h (4, 6) and 24h (10, 24) with p value < 0.001. Postoperative opioid requirement was significantly higher in the control group (30/30{100%}) than the study group (13/30{43.3%}). The median (interquartile range) number of opioid doses was significantly higher in the placebo group compared with the study group; 2(2, 2) and 0(0, 1) respectively. At all points in the study, pain scores both were lower in the study group (p < 0.0001). Conclusion: The modified surgeon assisted bilateral TAP block is relatively new, safe and cost effective technique which provides adequate postoperative analgesia allowing for better maternal ambulation and better postoperative recovery. Trial registration: Clinicaltrial.gov registration number: NCT04623632

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