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

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)

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S539-S539
Author(s):  
Beatriz Quiambao ◽  
Paula Peyrani ◽  
Chris Webber ◽  
Marie Van Der Wielen ◽  
Veronique Bianco ◽  
...  

Abstract Background The quadrivalent meningococcal ACWY polysaccharide tetanus toxoid conjugate vaccine (MenACWY-TT; Nimenrix) is licensed in various countries to prevent disease caused by meningococcal serogroups A, C, W, and Y. In a previous study (NCT00464815), subjects aged 11‒17 years received a primary dose of MenACWY-TT or a quadrivalent polysaccharide vaccine (MenACWY-PS). Here, we report the long-term antibody persistence of the primary dose and the immunogenicity and safety of a booster dose given 10 years after primary vaccination of subjects. Methods Participants were enrolled from the Philippines and received a booster dose of MenACWY-TT at 10 years postvaccination. Antibody persistence 10 years postprimary vaccination and immunogenicity 1 month after the booster dose were evaluated by serum bactericidal activity assays using rabbit complement (rSBA) to assess the percentages of subjects with titers ≥1:8 and ≥1:128 and geometric mean titers (GMTs) for each serogroup. Safety was assessed for the booster dose. Results Of 229 subjects enrolled in this extension study, 169 and 58 subjects in the MenACWY-TT and MenACWY-PS groups, respectively, completed the booster phase. The percentages of primary MenACWY-TT recipients with prebooster rSBA titers ≥ 1:8 and ≥ 1:128 at year 10 ranged from 71.6%‒90.7% and 64.8%‒85.2% for all serogroups, respectively, compared with 43.1%‒82.4% and 25.5%‒76.5% of primary MenACWY-PS recipients; rSBA GMTs for all serogroups were higher in the MenACWY-TT group than in the MenACWY-PS group at year 10. For the MenACWY-TT and MenACWY-PS groups, respectively, the MenACWY-TT booster dose elicited rSBA titers ≥1:8 in 100% and ≥98.0% of subjects (figure); 100% and ≥96.1% of all subjects had titers ≥1:128. For all serogroups, rSBA GMTs at 1 month after the booster dose were higher than before the booster dose. No new safety signals were observed during the booster phase. Conclusion Functional antibody responses elicited by MenACWY-TT persisted 10 years after primary vaccination; the booster dose was well tolerated and elicited robust immune responses. ClinicalTrials.gov: NCT03189745, EudraCT # 2013-001512-29. Funded by Pfizer. Disclosures All authors: No reported disclosures.


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S960-S961
Author(s):  
Beatriz Quiambao ◽  
Paula Peyrani ◽  
Chris Webber ◽  
Marie Van Der Wielen ◽  
Veronique Bianco ◽  
...  

Abstract Background The quadrivalent meningococcal ACWY polysaccharide tetanus toxoid conjugate vaccine (MenACWY-TT; Nimenrix) is licensed in various countries to prevent disease caused by meningococcal serogroups A, C, W, and Y. In a previous study (NCT00464815), subjects aged 11‒17 years received a primary dose of MenACWY-TT or a quadrivalent polysaccharide vaccine (MenACWY-PS). Here, we report the long-term antibody persistence of the primary dose and the immunogenicity and safety of a booster dose given 10 years after primary vaccination of subjects. Methods Participants were enrolled from the Philippines and received a booster dose of MenACWY-TT at 10 years postvaccination. Antibody persistence 10 years postprimary vaccination and immunogenicity 1 month after the booster dose were evaluated by serum bactericidal activity assays using rabbit complement (rSBA) to assess the percentages of subjects with titers ≥ 1:8 and ≥ 1:128 and geometric mean titers (GMTs) for each serogroup. Safety was assessed for the booster dose. Results Of 229 subjects enrolled in this extension study, 169 and 58 subjects in the MenACWY-TT and MenACWY-PS groups, respectively, completed the booster phase. The percentages of primary MenACWY-TT recipients with prebooster rSBA titers ≥ 1:8 and ≥ 1:128 at year 10 ranged from 71.6%‒90.7% and 64.8%‒85.2% for all serogroups, respectively, compared with 43.1%‒82.4% and 25.5%‒76.5% of primary MenACWY-PS recipients; rSBA GMTs for all serogroups were higher in the MenACWY-TT group than in the MenACWY-PS group at year 10. For the MenACWY-TT and MenACWY-PS groups, respectively, the MenACWY-TT booster dose elicited rSBA titers ≥ 1:8 in 100% and ≥ 98.0% of subjects (figure); 100% and ≥ 96.1% of all subjects had titers ≥ 1:128. For all serogroups, rSBA GMTs at 1 month after the booster dose were higher than before the booster dose. No new safety signals were observed during the booster phase. Conclusion Functional antibody responses elicited by MenACWY-TT persisted 10 years after primary vaccination; the booster dose was well tolerated and elicited robust immune responses. ClinicalTrials.gov NCT03189745, EudraCT # 2013-001512-29. Funded by Pfizer. Disclosures All authors: No reported disclosures.


2014 ◽  
Vol 22 (2) ◽  
pp. 185-192 ◽  
Author(s):  
Juan Carlos Tinoco ◽  
Christine Juergens ◽  
Guillermo M. Ruiz Palacios ◽  
Jorge Vazquez-Narvaez ◽  
Hermann Leo Enkerlin-Pauwells ◽  
...  

ABSTRACTThis open-label multicenter clinical trial conducted in Mexico assessed the immunogenicity and safety of a 13-valent pneumococcal conjugate vaccine (PCV13) in adults ≥50 years of age not previously vaccinated with the 23-valent pneumococcal polysaccharide vaccine (PPSV23). The PCV13 elicited a robust immune response in this study population, as reflected by the magnitude of fold rises in functional antibody levels measured by serotype-specific opsonophagocytic activity (OPA) assays before and 1 month after vaccination. Although the prevaccination OPA geometric mean titers (GMTs) for the majority of the serotypes were significantly lower in the 50- to 64-year age group than those in the ≥65-year age group, the postvaccination immune responses were generally similar. The overall immune responses were higher for the majority of the serotypes in the Mexican study population than those in similar adult study populations who received the PCV13 in Europe and the United States. PCV13 was well tolerated, and there were no vaccine-related serious adverse events. In conclusion, PCV13 is safe and immunogenic when administered to adults ≥50 years of age in Mexico and has the potential to protect against vaccine-type pneumococcal disease. (This study has been registered at ClinicalTrials.gov under registration no. NCT01432262.)


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S378-S378
Author(s):  
Shon A Remich ◽  
Nicholas Kitchin ◽  
Michael W Pride ◽  
Annaliesa S Anderson ◽  
Ping Li ◽  
...  

Abstract Background Clostroidides difficile (C difficile) is a common cause of antibiotic-associated diarrhea. To date, there is no vaccine to prevent C. difficile infection (CDI). This extension of a phase 2 study explores the immunogenicity, safety, and tolerability of a 4th dose, and antibody persistence of a three-dose regimen of a toxoid-based C difficile vaccine in 300 healthy adults 65 to 85 years of age in the United States. Methods The first stage of this study was conducted from 16 July 2015 to 7 March 2017, in which subjects were enrolled and randomized to receive one of two antigen dose levels (100µg or 200µg total toxoid A and B) or placebo, administered in one of two three-dose regimens: Days 1, 8 & 30 or Months 0, 1 & 6. Immunogenicity testing was conducted on samples obtained at each of nine study visits through 12 months post dose 3. In this extension stage, subjects who had received vaccine in the first stage were re-randomized at 12 months post dose 3 to receive either a booster dose or placebo in a 1:1 ratio. Subjects were followed for immunogenicity three (3) years post booster (four years post dose #3) Results Peak antibody response to vaccination was observed between day 8 and 30 following booster administration. Both regimens demonstrated robust anamnestic responses with peak levels above the three-dose peak (stage 1). Toxin A geometric mean concentrations (GMCs) remained above pre-booster GMCs, 3 years post booster for both dose levels and regimens. Antibody persistence for both groups demonstrated stable antibody levels four years after the primary vaccination series among subjects who did not receive a booster dose. No Grade 4 reactogenicity was reported during the study. Pain was the most common local reaction. Adverse event rates per subject were similar between both regimens and placebo. There were no Serious Adverse Events (SAEs) considered related to the investigational product at any dose or regimen. The safety profile was consistent with what was seen in the first stage of the study. Conclusion A booster dose of Clostroidides difficile vaccine candidate is highly immunogenic, well tolerated and demonstrates an acceptable safety profile in both dose groups for the Day and the Month regimens. Antibody persistence remains stable from 12 months to 4-year post dose 3. Disclosures Nicholas Kitchin, MD, Pfizer, Inc (Employee) Michael W. Pride, PhD, Pfizer (Employee, Shareholder) Annaliesa S. Anderson, PhD, Pfizer (Employee, Shareholder) Chris Webber, MD, Pfizer Inc (Employee, Shareholder)


F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 631
Author(s):  
Rachel C. Pieciak ◽  
Christopher J. Gill

Background: The technically complex pneumococcal conjugate vaccine (PCV) is arguably one of the most important and widely studied vaccines since the Hib vaccine. Given the complexity of its design, the cost of administering the PCV is tremendous. While we cannot make adjustments to the vaccine itself post licensure, we can manipulate the dosing schedule. And yet little work has been done to understand the differences in immune responses across different dosing schedules. Methods: Accordingly, we conducted a review of three recently published randomized control trials that compared immune responses across commonly used vaccine schedules in both high- and low-income countries. Results: Each of these studies assessed how changes to the number of doses, spacing between doses and the use/timing of a booster dose affected ELISA geometric mean concentrations post-primary and post-booster dose. If the goal is to administer vaccinations in the most immunologically efficient manner as possible, evidence from these studies would suggest that several commonly used vaccine schedules are missing the mark. Conclusions: In order to deliver the most “bang for its buck”, PCV dosing schedules should not only leverage convenience but also immunological data. Without the reexamination of PCV schedules the status quo will remain inefficient, ineffective and needlessly expensive, threatening the sustainability of its implementation long-term.


2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S322-S322 ◽  
Author(s):  
Terry Nolan ◽  
Hartley Garfield ◽  
Anil Gupta ◽  
Murdo Ferguson ◽  
Helen Marshall ◽  
...  

Abstract Background This phase 3b, open label, controlled, multi-center, extension study (NCT02446743) assessed the persistence of bactericidal activity at 4 years post-primary vaccination with a recombinant, 4-component, meningococcal serogroup B vaccine (4CMenB) in adolescents who participated in the parent study NCT01423084 and their response to a booster dose, compared with that in vaccine-naïve healthy controls. Methods Adolescents and young adults previously primed with 4CMenB (2 doses; following a 0,1-month schedule) in study NCT01423084 (group 3B) and vaccine-naïve 15–22 year olds (group B0_1) were enrolled. Group 3B received a booster dose of 4CMenB at 4 years post-primary vaccination; group B0_1 received 2 catch-up doses of 4CMenB (following a 0,1-month schedule). Antibody persistence (primary objective) was evaluated at 4 years post-primary vaccination (in group 3B) vs. baseline (in group B0_1) using human serum bactericidal assay (hSBA), in terms of geometric mean titer (GMT) and percentage (%) of individuals with hSBA titer at least 4. Immune responses at 1 month after booster dose (in group 3B) vs. those at 1 month after first dose (in group B0_1) were also assessed. Results In group 3B, antibody levels declined from 1 month to 4 years post-primary vaccination against all antigens except NHBA, but were higher than in group B0_1 at baseline (Table), with a GMT ratio ≥1.3 and a difference in % of individuals with hSBA titer at least 4 of ≥9%. After one dose of 4CMenB (booster in 3B or first dose in B0_1), GMTs increased (≥4.6-fold in group 3B; ≥2.3-fold in group B0_1), and ≥94% of participants in group 3B and ≥41% of participants in group B0_1 had hSBA titer at least 4 (Table). Conclusion Antibody levels in adolescents and young adults primed with 4CMenB waned over time but were higher at 4 years post-primary vaccination than for vaccine-naïve individuals at baseline. A booster dose of 4CMenB in vaccine-primed individuals elicited higher immune responses than one dose of 4CMenB in vaccine-naïve individuals. The research was supported by GlaxoSmithKline Biologicals SA. Disclosures T. Nolan, GSK group of companies: Research Contractor and Scientific Advisor, Research grant. Pfizer: Research Contractor, Research grant. H. Garfield, Novartis/GSK group of companies: Investigator, Research support. A. Gupta, Novartis/GSK group of companies: Investigator, payment for research-related activities; M. Ferguson, GSK group of companies: Investigator, I receive salary from CRG. CRG has contracts with GSK. H. Marshall, GSK group of companies: Grant Investigator and Investigator, Research grant. Pfizer: Grant Investigator and Investigator, Research grant; sanofi pasteur: Grant Investigator, Research grant. Novavax: Investigator, Research grant. D. D’Agostino, GSK group of companies: Consultant, Consulting fee. D. Toneatto, GSK group of companies: Employee, Salary.


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S959-S959
Author(s):  
James Hedrick ◽  
Michael W Simon ◽  
Shane Christensen ◽  
German Anez ◽  
Judy Pan ◽  
...  

Abstract Background The MenACYW-TT conjugate vaccine is a quadrivalent meningococcal vaccine that contains tetanus toxoid as carrier protein. Vaccine is intended for global use in all age groups (i.e., individuals 6 weeks of age and older). This Phase III study evaluated the safety and immunogenicity of the vaccine when compared with a licensed quadrivalent meningococcal conjugate vaccine in individuals ≥ 15 years of age. Methods A randomized, modified double-blind study (NCT02752906) was conducted in the United States and Puerto Rico. The study evaluated 810 participants primed with a licensed quadrivalent meningococcal conjugate vaccine (Menactra® [MenACWY-D] or MENVEO® [MenACWY-CRM]) in the 4 to 10 years prior to enrollment. Participants were randomly assigned to receive either a single booster dose of MenACYW-TT conjugate vaccine or MenACWY-D. Safety data were collected up to 6 months post-vaccination. Results Non-inferiority of immune response was demonstrated for MenACYW-TT vs. MenACWY-D based on percentages of participants achieving an serum bactericidal assay with human complement (hSBA) seroresponse for serogroups A, C, W, and Y at Day 30 post-vaccination. Post-vaccination hSBA geometric mean titers (GMTs) were higher following administration of MenACYW-TT compared with MenACWY-D for age subgroups ≥15 to < 18 years and ≥18 years. Relative to MenACWY-D, post-vaccination hSBA GMTs were higher for all 4 serogroups following administration of MenACYW-TT in participants who received the priming vaccine < 7 years prior to the booster; for participants who received priming vaccine ≥7 years prior to booster, post-vaccination GMTs were higher for serogroups C, W and Y, and comparable for serogroup A. In MenACWY-CRM-primed subjects, hSBA vaccine seroresponse rates were comparable for all 4 serogroups regardless of the booster vaccine administered. In MenACWY-D-primed subjects, hSBA seroresponse rates following MenACYW-TT booster administration were comparable for serogroups A and Y, and higher for serogroups C and W. Reactogenicity profiles were comparable across study groups. Conclusion MenACYW-TT conjugate vaccine was immunogenic and well tolerated when administered as a booster dose to individuals ≥15 years of age. Disclosures All authors: No reported disclosures.


Vaccines ◽  
2019 ◽  
Vol 7 (4) ◽  
pp. 139
Author(s):  
Petráš ◽  
Oleár ◽  
Molitorisová ◽  
Dáňová ◽  
Čelko ◽  
...  

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.


2019 ◽  
Vol 12 (9) ◽  
pp. 1422-1427
Author(s):  
Jayalakshmi Vasu ◽  
Mouttou Vivek Srinivas ◽  
Prabhakar Xavier Antony ◽  
Jacob Thanislass ◽  
Vijayalakshmi Padmanaban ◽  
...  

Background and Aim: Canine parvovirus (CPV) is the most important viral cause of enteritis and mortality in pups. Evaluation and monitoring of pre- and post-vaccine immune responses may help to determine the efficacy of the current vaccination schedule being followed in pups in India. This study aimed to evaluate and monitor the pre- and post-vaccine immune responses of CPV vaccinated pups using hemagglutination inhibition (HI) assay. The neutralizing antibody titer levels were also detected using serum neutralization test (SNT). Materials and Methods: The pups were categorized into two groups, the double booster and the single booster groups. In this study, serum samples were subjected to HI and SNT for measuring the CPV antibody titer at frequent intervals for up to 6 months from 27 healthy pups following primary and booster CPV vaccinations. Results: The antibody titers in double booster pups reached their peaks at the 21st day after the second booster vaccination with a geometric mean (GM) of 3.57. The antibody titers in single booster pups reached their peaks at the 21st day after the first booster vaccination with a lower GM of 3.18. Conclusion: The double booster pups maintained a higher immune response throughout the period of the study compared to single booster pups though the difference in titers was not statistically significant. SNT results indicated that the raised antibody titer was also able to yield virus-neutralizing antibodies. No interfering maternally derived antibodies were found in the pups at the age of primary vaccination (45th day) in our study. Therefore, the second booster vaccination may be useful in maintaining the protective titer for a prolonged period.


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