Quadrivalent Meningococcal Conjugate Vaccine Research Articles

Safety and immunogenicity of a pentavalent meningococcal conjugate vaccine versus a quadrivalent meningococcal conjugate vaccine in adults in India: an observer-blind, randomised, active-controlled, phase 2/3 study

Meningococcal disease remains an important public health problem globally. We assessed the non-inferiority and the lot-to-lot consistency of a pentavalent meningococcal ACYWX conjugate vaccine (NmCV-5; Serum Institute of India, Pune, India) versus a quadrivalent meningococcal ACWY conjugate vaccine (MenACWY-D) in healthy adults. In this observer-blind, randomised, active-controlled, phase 2/3 study, healthy adults aged 18-85 years were recruited from nine hospitals across seven cities in India. Participants were grouped by age (age 18-29, 30-60, and 61-85 years), and within each age group they were randomly assigned (3:1) to receive either NmCV-5 or MenACWY-D (Sanofi Pasteur). In the age 18-29 years group, participants were additionally randomly assigned (1:1:1:1) to either lot A, lot B, or lot C of NmCV-5 or MenACWY-D. Block randomisation was used (block sizes of 4, 8, and 12). Study participants and study personnel were masked to treatment assignment. Participants received either a 0·5 mL dose of NmCV-5, containing 5 μg each of conjugated A, C, W, Y, and X polysaccharides, or 0·5 mL MenACWY-D, containing 4 μg of each of conjugated A, C, W, and Y polysaccharides. Vaccinations were administered intramuscularly in the deltoid muscle. The primary outcomes were seroresponse (non-inferiority margin of -10%) and geometric mean titres (GMTs; non-inferiority margin of 0·5) in all participants, and lot-to-lot consistency of NmCV-5 (in participants aged 18-29 years; consistency was shown if the geometric mean ratio [GMR] 95% CIs were within the limit interval of 0·5 to 2). For non-inferiority, serogroup X immune response in the NmCV-5 group was compared with the lowest immune response among serogroups A, C, W, and Y in the MenACWY-D group. Immunogenicity was assessed with a serum bactericidal activity assay that used baby rabbit serum as the complement (rSBA) on days 1 and 29 in the modified per-protocol population (including all participants who were randomly assigned, received vaccine, had a post-vaccination rSBA measurement up to 121 days after vaccination, and no major protocol violations). Solicited events were collected for 7 days and serious adverse events were collected for 180 days, and assessed in the safety population (all participants who received vaccination). This study is registered with ClinicalTrials.gov, NCT04358731, and CTRI, CTRI/2019/12/022436, and is now complete. Between Dec 27, 2019, and Sept 19, 2020, 1712 individuals were screened, of whom 1640 were randomly assigned and received NmCV-5 (n=1233) or MenACWY-D (n=407; mean age 26·4 years [SD 12·2], 551 [33·6%] of 1640 were female, and 1089 [66·4%] were male). 1441 participants were aged 18-29 years (362 received lot A, 360 received lot B, and 361 received lot C of NmCV-5 and 357 received MenACWY-D, with one participant mis-randomised by age group and excluded from lot-to-lot consistency analysis). Non-inferiority of NmCV-5 against MenACWY-D was met in terms of seroresponse rates and GMT ratios for all five serogroups. The seroresponse rates were 84·3% (97·5% CI 81·7 to 86·7; serogroup A) or higher in the NmCV-5 group and 54·5% (48·5 to 60·3; serogroup A) or higher in the MenACWY-D group, with the difference in the seroresponse rate between vaccine groups ranging from 0·2 (97·5% CI -2·2 to 2·6) for serogroup W to 29·8 (24·4 to 35·2) for serogroup A. GMTs on day 29 were 7016·9 (97·5% CI 6475·7 to 7603·4; serogroup Y) or higher in the NmCV-5 group and 3646·8 (3188·2 to 4171·5; serogroup Y) or higher in the MenACWY-D group, with GMT ratios between vaccine groups for serogroups A, C, Y, and W ranging from 1·9 (97·5% CI 1·5-2·3) for serogroup W to 2·5 (2·2-2·8) for serogroup A. NmCV-5 induced robust immune responses against serogroup X. Lot-to-lot consistency of NmCV-5 was found for all five serogroups, with 95% CIs for the GMT ratio for each pair of lots being between 0·5 and 2: the lowest lower bound and the highest upper bound of the 95% CI for the GMR between NmCV-5 lot A and lot B were 0·6 and 1·4, between lot A and lot C were 0·7 and 1·6, and between lot B and lot C were 0·8 and 1·6, respectively, for any of the five serogroups. At least one solicited adverse event was reported by 527 (42·7%) of 1233 participants in the NmCV-5 group and 142 (34·9%) of 407 in the MenACWY-D group. No serious adverse events occurred that were determined to be causally related to vaccination. NmCV-5 was non-inferior to MenACWY-D in terms of seroresponse and GMTs, was safe, and demonstrated lot-to-lot consistency. NmCV-5 is prequalified by WHO and was rolled out in the African meningitis belt in April, 2024. Serum Institute of India.

National Vaccination Coverage Among Adolescents Aged 13-17 Years - National Immunization Survey-Teen, United States, 2023.

Based on safety and efficacy data, vaccinations are the best defense to protect persons and communities from serious vaccine-preventable diseases. The Advisory Committee on Immunization Practices recommends routine vaccination of adolescents aged 11-12 years with three vaccines including tetanus, diphtheria, and acellular pertussis vaccine; quadrivalent meningococcal conjugate vaccine; and human papillomavirus vaccine. CDC analyzed data from the 2023 National Immunization Survey-Teen for 16,658 adolescents aged 13-17 years (born during January 2005-December 2010) to assess vaccination coverage in 2023, recent trends in coverage by birth year, and trends in coverage by eligibility for the Vaccines for Children (VFC) program and birth year. In 2023, coverage with all routine vaccines recommended for adolescents was similar to coverage in 2022. Vaccination coverage among VFC-eligible adolescents was generally stable during the COVID-19 pandemic, except for a decrease in the percentage of VFC-eligible adolescents who were up to date with HPV vaccination by age 13 years among those born in 2010 compared with those born in 2007. Whereas coverage differences were found between VFC-eligible and non-VFC-eligible adolescents before the COVID-19 pandemic, coverage was similar among the most recent birth years in the survey. Providers should make strong recommendations for all routine vaccines and review adolescent vaccination records to verify if adolescents are up to date with all recommended vaccines.

Effectiveness of quadrivalent meningococcal conjugate vaccine against meningococcal carriage and genotype character changes: A secondary analysis of prospective cohort study in Korean military trainees

ObjectiveWe evaluated the changes and molecular epidemiology of meningococcal carriage in military recruits after quadrivalent meningococcal conjugate vaccines (MenACWY) vaccination. MethodsOropharyngeal swabs were obtained at the beginning and end of the 5-week training. Carriage rates before and after vaccination were compared to estimate vaccine effectiveness (VE). Cultured isolates were characterized by multi-locus sequence typing (MLST). ResultsOf 866 vaccinated participants, the overall carriage rate was 10.6% prior to MenACWY vaccination and it tended to decrease to 9.5% after 5 weeks of vaccination (P = 0.424). Carriage rate of serogroup ACWY decreased significantly after vaccination (VEACWY = 72.6%, 95% CI: 36.3-88.2), and serogroup C was particularly reduced (VEC = 83.0%, 95% CI: 50.6-94.1), whereas non-groupable isolates increased significantly after vaccination (VENG = -76.1%, 95% CI: -176.2 to -13.1). Among 99 carriage isolates with complete MLST profiles, 45 different sequence types with nine clonal complexes (CCs) were identified, and 35.3% of the carriage isolates belonged to hypervirulent strains such as CC-32, CC-41/44, and CC-269. ConclusionsMenACWY vaccination in military recruits led to reduced carriage rates of serogroups C, W, and Y within a short 5-week period. However, serogroup B isolates belonging to the hypervirulent lineage remained after the implementation of MenACWY vaccination.

Use of the Pfizer Pentavalent Meningococcal Vaccine Among Persons Aged ≥10 Years: Recommendations of the Advisory Committee on Immunization Practices - United States, 2023.

Meningococcal disease is a life-threatening invasive infection caused by Neisseria meningitidis. Two quadrivalent (serogroups A, C, W, and Y) meningococcal conjugate vaccines (MenACWY) (MenACWY-CRM [Menveo, GSK] and MenACWY-TT [MenQuadfi, Sanofi Pasteur]) and two serogroup B meningococcal vaccines (MenB) (MenB-4C [Bexsero, GSK] and MenB-FHbp [Trumenba, Pfizer Inc.]), are licensed and available in the United States and have been recommended by CDC's Advisory Committee on Immunization Practices (ACIP). On October 20, 2023, the Food and Drug Administration approved the use of a pentavalent meningococcal vaccine (MenACWY-TT/MenB-FHbp [Penbraya, Pfizer Inc.]) for prevention of invasive disease caused by N. meningitidis serogroups A, B, C, W, and Y among persons aged 10-25 years. On October 25, 2023, ACIP recommended that MenACWY-TT/MenB-FHbp may be used when both MenACWY and MenB are indicated at the same visit for the following groups: 1) healthy persons aged 16-23 years (routine schedule) when shared clinical decision-making favors administration of MenB vaccine, and 2) persons aged ≥10 years who are at increased risk for meningococcal disease (e.g., because of persistent complement deficiencies, complement inhibitor use, or functional or anatomic asplenia). Different manufacturers' serogroup B-containing vaccines are not interchangeable; therefore, when MenACWY-TT/MenB-FHbp is used, subsequent doses of MenB should be from the same manufacturer (Pfizer Inc.). This report summarizes evidence considered for these recommendations and provides clinical guidance for the use of MenACWY-TT/MenB-FHbp.

1157. Immune Persistence and Booster Response of a Quadrivalent Meningococcal Conjugate Vaccine (MenACYW-TT) 5 Years After Primary Vaccination of Adults ≥59 Years of Age

Abstract Background MenACYW-TT (MenQuadfi®, Sanofi) is a quadrivalent (serogroups A, C, W, and Y) meningococcal tetanus toxoid conjugate vaccine. It is approved for use in persons aged ≥2 years in the US and persons aged ≥1 year in Europe and certain other countries; trials in infants as young as 6 weeks are ongoing. The second stage of a 2-stage study of MenACYW-TT, reported herein, evaluated immune persistence among older adults who received primary vaccination with either quadrivalent meningococcal polysaccharide vaccine (MSPV4) or MenACYW-TT five years earlier at age ≥ 56 years. The immunogenicity and safety of a MenACYW-TT booster dose given to this population were also evaluated. Methods This was a Phase 3, 2-stage, randomized, open-label, multi-center study (NCT04142242) of adults aged ≥59 years who participated in previous studies of MenACYW-TT vs MPSV4 (NCT01732627 and NCT02842866). The study was conducted in the US and Puerto Rico. Immune persistence and response were assessed with a serum bactericidal assay using human complement (hSBA). Safety data were collected for up to 30 days after booster vaccination. All analyses were descriptive. Results Of the initial study population (N=471), 70 adults participated in Stage II of the study. At 5 years post-primary vaccination, seroprotection (hSBA ≥ 1:8) rates (SPRs) and hSBA geometric mean titers (GMTs) declined in both MenACYW-TT- and MPSV4-primed subjects, with SPRs and hSBA GMTs for serogroups A, C, W, and Y trending higher in MenACYW-TT- vs MPSV4-primed subjects (Table 1). Thirty days after booster vaccination, hSBA GMTs and SPRs increased from pre-booster for all serogroups and were, along with seroresponse rates, higher in MenACYW-TT-primed subjects compared to MPSV4-primed subjects (Table 2). Rates of AEs following booster vaccination were similar regardless of priming vaccine. No safety concerns were identified. Conclusion Five years after primary vaccination, immune persistence tended to be greater for MenACYW-TT vs MPSV4. A MenACYW-TT booster was well tolerated and immunogenic in adults ≥ 61 years, when administered 5 years after primary vaccination with either MPSV4 or MenACYW-TT. Disclosures Corwin A. Robertson, MD, MPH, FACP, Sanofi: Sanofi employee|Sanofi: Sanofi's Employee|Sanofi: Stocks/Bonds Katherine Galarza, MD, Sanofi: Sanofi employee|Sanofi: Stocks/Bonds Alexandre Selmani, PhD, Sanofi: Sanofi employee|Sanofi: Stocks/Bonds Philipp Oster, MD, Sanofi: Sanofi employee

1139. Immunogenicity and Safety Study of a Quadrivalent Meningococcal Conjugate Vaccine (MenACYW-TT) Compared to a Meningococcal Reference Vaccine (MCV4-TT) in Healthy Adolescents

Abstract Background MenACYW-TT (MenQuadfi®) is a quadrivalent meningococcal conjugate vaccine licensed for use in individuals ≥ 12 months age in the EU and certain other countries and ≥ 2 years of age in the US. Safety and immunogenicity of a single dose of MenACYW-TT were evaluated in 10-17 years old healthy adolescents vs a quadrivalent (MCV4-TT [Nimenrix®]) meningococcal vaccine licensed ex-US. Co-administration of MenACYW-TT with 9vHPV and Tdap-IPV vaccines was also studied. Methods In this modified double-blind, Phase-3 study (NCT04490018) conducted in Hungary, Italy, Spain, and Singapore, meningococcal vaccine-naïve adolescents or MenC-primed (when < 2 years of age) were randomized to receive either MenACYW-TT or MCV4-TT and co-administration with 9vHPV and Tdap-IPV vaccines. Serum bactericidal assays with human complement (hSBA) were used to measure anti-meningococcal antibodies against all 4 serogroups at baseline and 30 days post-vaccination. Antibodies against antigens contained in Tdap-IPV and 9vHPV were also measured. Safety data were collected within 30 days post-vaccination. Results A total of 463 subjects were enrolled in this study. Non-inferiority between MenACYW-TT and MCV4-TT, based on seroprotection rate (percentage of subjects achieving hSBA titers ≥ 1:8), was demonstrated for all 4 serogroups one month following meningococcal vaccination. Thirty days post vaccination, hSBA geometric mean titers (GMTs) were higher for MenACYW-TT vs MCV4-TT for serogroups C, Y and W, and comparable for serogroup A. The percentages of subjects with an hSBA vaccine seroresponse were higher for MenACYW-TT vs MCV4-TT for all 4 serogroups (Table). When MenACYW-TT was administered alone or concomitantly with 9vHPV and Tdap-IPV vaccines, the immunogenicity results were comparable or higher in subjects receiving MenACYW-TT alone than in those receiving all vaccines concomitantly. The safety profiles were comparable between MenACYW-TT and MCV4-TT, administered alone or concomitantly with 9vHPV and Tdap-IPV vaccines, with no safety concerns observed during this study. Conclusion The trial met the primary objective. MenACYW-TT induced non-inferior immune responses to all serogroups based on seroprotection rates, and higher or comparable GMTs and seroresponse rates compared to MCV4-TT. Disclosures Céline Zocchetti, MSc, Sanofi: Stocks/Bonds Olga Syrkina, MD, Sanofi: Stocks/Bonds Siham Bchir, MSc, Sanofi: Sanofi's Employee|Sanofi: Stocks/Bonds Isabelle Bertrand-Gerentes, MD, Sanofi: Stocks/Bonds

A Multivariate Probit Regression of the Uptake of Adolescent Vaccines Among Racial/Ethnic Minority Adolescents Before and During the COVID-19 Pandemic

PurposeThe uptake of adolescent vaccines has improved over the years. However, research of the effects of the COVID-19 pandemic on this uptake among racial/ethnic minority adolescents has been limited. This study was conducted to compare the probability of uptake of the human papillomavirus (HPV); tetanus, diphtheria, and acellular pertussis (Tdap); and quadrivalent meningococcal conjugate (MenACWY) vaccines among racial/ethnic minority adolescents ages 13–17 years in 2019, 2020, and 2021. MethodsUsing a cross-sectional design to examine data from the National Immunization Survey–Teen (2019–2021), multivariate probit regression was used to model variation in uptake of these three adolescent vaccines (n = 38,128). The outcome measures were HPV, Tdap, and MenACWY vaccine uptake. ResultsThe probability of uptake of HPV vaccine was higher in 2020 (Coef = 0.09 [95% confidence interval (CI), 0.03–0.16]) and 2021 (Coef = 0.07 [95% CI, 0.00–0.15]) than in 2019. The probability of uptake of MenACWY vaccine was higher in 2020 (Coef = 0.08 [95% CI, 0.02–0.15]) than in 2019. The probability of uptake of recommended vaccines varied among racial/ethnic minorities with non-Hispanic Black adolescents exhibiting higher probability of uptake of HPV vaccine (Coef = 0.10 [95% CI, 0.01–0.19]) than Tdap vaccine. U.S. Census region and insurance status were associated with the uptake of all recommended vaccines. DiscussionProgress in the uptake of these recommended vaccines may not have been interrupted by the COVID-19 pandemic. Also, disparities in uptake of the recommended vaccines still exist despite increased uptake during the pandemic. Future research should examine the disparities as well as examine regional differences in the uptake of these three adolescent vaccines.

Structured Benefit-Risk Assessment of a New Quadrivalent Meningococcal Conjugate Vaccine (MenACYW-TT) in Individuals Ages 12 Months and Older.

A favorable benefit-risk balance is required to support licensure of biologics, in keeping with regulatory agencies' evolving recommendations, including the United States Food and Drugs Administration. We present a structured semi-quantitative benefit-risk analysis of MenACYW-TT, a quadrivalent meningococcal conjugate vaccine against Neisseria meningitidis serogroups, A, C, W and Y versus licensed comparators in individuals aged ≥ 12 months. We used data from six MenACYW-TT clinical trials, stratified by age group, versus licensed vaccines: toddlers (12-23 months; Nimenrix® [MCV4-TT]), children (2-9 years; Menveo® [MCV4-CRM]), adolescents (10-17 years; MCV4-CRM or Menactra® [MCV4-DT]), adults (18-55 years; MCV4-DT) and older adults (≥ 56 years; Menomune®-A/C/Y/W-135 [MPSV4]). Eight benefit (seroresponse and seroprotection for A, C, W and Y) and five risk outcomes (any and grade 3 solicited injection site and systemic reactions, and serious adverse events) were measured at Day 30 after initial vaccination. Analyses were conducted by baseline vaccination status (meningococcal vaccine-naïve or vaccine-primed). MenACYW-TT showed favorable seroresponse and seroprotection among vaccine-naïve participants aged ≥ 2years, against all serogroups, compared with MCV4-CRM, MCV4-DT and MPSV4. In vaccine-naïve toddlers, there was a favorable effect for serogroup C, but no difference between MenACYW-TT and MCV4-TT for serogroups A, Y and W. A favorable effect for MenACYW-TT against serogroup C was observed in all vaccine-naïve and combined vaccine-naïve and MenC conjugate vaccine-primed groups. For all risk criteria, there were no differences between MenACYW-TT and MCV4s in toddlers, children, adolescents and adults. Results for solicited injection site and systemic reactions favored MPSV4 in older adults. The benefit-risk profile for MenACYW-TT showed favorable seroresponse and seroprotection in individuals aged ≥ 2 years and no difference in risk criteria between MenACYW-TT and MCV4s. MenACYW-TT may provide an alternative to the standard-of-care for meningococcal disease prevention in those aged ≥ 12 months.

Immunogenicity and safety of a pentavalent meningococcal ABCWY vaccine in adolescents and young adults: an observer-blind, active-controlled, randomised trial

Immunogenicity and safety of a pentavalent meningococcal ABCWY vaccine in adolescents and young adults: an observer-blind, active-controlled, randomised trial

Safety and immunogenicity of quadrivalent meningococcal polysaccharide vaccine (MPV ACYW135) compared with quadrivalent meningococcal conjugate vaccine (Menactra®) in Malian children

ABSTRACT Affordable, polyvalent meningococcal vaccines are needed for use in emergency reactive immunization campaigns. A phase IV randomized, observer-blind, controlled study compared the safety and immunogenicity of a quadrivalent meningococcal polysaccharide vaccine (MPV-4, MPV ACYW135) and quadrivalent meningococcal ACWY conjugate vaccine (MCV-4, Menactra®). Healthy, 2- to 10-year-old children in Bamako, Mali, were randomized 1:1 to receive one dose of MPV-4 or MCV-4. Safety outcomes were evaluated for 6 months post-immunization. Immunogenicity for all serogroups was assessed for non-inferiority between MPV-4 and MCV-4 30 days post immunization by serum bactericidal antibody assay using baby rabbit complement (rSBA). From December 2020 to July 2021, 260 healthy subjects were consented and randomized. At Day 30 post-immunization, the proportions of subjects with rSBA titers ≥ 128 for all serogroups in the MPV-4 group were non-inferior to those in MCV-4 group. The proportions of subjects with rSBA ≥ 4-fold increase and rSBA titers ≥ 8 for all serogroups were similar among vaccine groups (P > .05). Geometric Mean Titers and Geometric Mean Fold Increases for all serogroups in both vaccine groups were similar (P > .05). Few local and systemic post-immunization reactions of similar severity and duration were observed within 7 days and were similar in both groups (P > .05). All resolved without sequelae. Unsolicited adverse events were similar in both groups regarding relationship to study vaccine, severity and duration. No serious adverse events were reported during the study period. MPV ACYW135 showed a non-inferior immunogenicity profile and a comparable reactogenicity profile to MCV-4 in Malian children aged 2–10 years. Clinical Trial Registration: NCT04450498.

Immunogenicity of quadrivalent meningococcal conjugate vaccine in frequent platelet donors

AbstractFrequent plateletpheresis is associated with severe lymphopenia of uncertain clinical significance. We assessed the functional impact of frequent platelet donations and associated lymphopenia on the response to neoantigens. We conducted a prospective study of 102 platelet donors (HIV uninfected) who were naive to meningococcal vaccination recruited at Brigham and Women’s Hospital. One dose of quadrivalent meningococcal conjugate vaccine was administered. Seroresponse was defined as a fourfold increase of serum bactericidal antibody titers and seroprotection was defined as postvaccination titers of ≥1:8, for each of the 4 vaccine antigens (A, C, W, and Y). Mean age of participants was 61 years, 69% were male, and medial number of platelet donations in prior year was 14 (interquartile range, 4-20). Frequent platelet donors had a low CD4 count (14% with ≤200/μL and 34% with ≤350/μL). Seroresponse rates varied from 68% for serogroup Y to 86% for serogroup A and were higher for participants with baseline titers of <1:8. Postvaccination seroprotection rates varied from 76% for serogroup Y to 96% for serogroup A. After adjustments for age, sex, and frequent donations, lower total lymphocyte or lower CD4 counts were not associated with lower responses. These data suggest no impairment by plateletpheresis-associated lymphopenia on response to these neoantigens. This trial was registered at www.clinicaltrials.gov as #NCT04224311.

Expert Perspectives on the Vaccination of Individuals Who Are at Increased Risk of Meningococcal Disease Due to Medical Conditions: A Podcast.

Patients with functional or anatomic asplenia, including sickle cell anemia; complement component deficiency; or human immunodeficiency virus (HIV) infection have a significantly increased risk of developing meningococcal disease. The Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC) recommends vaccination with a quadrivalent meningococcal conjugate vaccine against serogroupsA, C, W, and Y (MenACWY) for individuals 2months of age or older who are diagnosed with functional or anatomic asplenia, complement component deficiency, or HIV infection. Vaccination with a meningococcal vaccine against serogroupB (MenB) is also recommended for individuals 10years of age or older who are diagnosed with functional or anatomic asplenia or complement component deficiency. Despite these recommendations, recent studies have shown that vaccination coverage in these populations is low. In this podcast, the authors discuss the challenges for implementing vaccine recommendations for individuals with medical conditions at increased risk of developing meningococcal disease and discuss strategies to increase coverage. Suboptimal vaccination rates could be addressed by better educating healthcare providers about recommendations for MenACWY and MenB vaccines in individuals at increased risk, increasing awareness of low vaccination coverage, and tailoring the education to the needs of particular healthcare providers and their respective patient populations. Barriers to vaccination could also be removed by administering vaccines at alternative sites of care, bundling preventative services, and implementing vaccination reminder systems that are tied to immunization information systems.

Immunogenicity and safety of a quadrivalent meningococcal conjugate vaccine (MenACYW-TT) administered as a booster to adults aged ≥59 years: A phase III randomized study

ABSTRACT This 2-stage Phase III study (NCT04142242) of a recently licensed quadrivalent meningococcal tetanus toxoid-conjugate vaccine (MenACYW-TT) assessed the safety and immunogenicity of a booster dose in older adults (≥59 years) primed with either MenACYW-TT or a quadrivalent meningococcal polysaccharide vaccine (MPSV4). Immune persistence of MenACYW-TT and MPSV4 after primary vaccination was also evaluated. During Stage I, the participants administered MPSV4 (n = 165) or MenACYW-TT (n = 236) 3 years previously were randomized 9:2 to receive either a MenACYW-TT booster or to have blood drawn for persistence only. Participants primed with MPSV4 or MenACYW-TT 6–7 years previously had blood drawn for antibody persistence only. A serum bactericidal assay using human complement was used to measure functional antibodies against each serogroup at baseline and, for those receiving a booster, 30 days post-vaccination (D30). Proportions of participants with seroresponse (post-vaccination titers ≥1:16 when baseline titers <1:8 or ≥ 4-fold increase when baseline titers ≥1:8) were determined. Safety data were collected up to D30. Seroresponse rates for all serogroups at D30 ranged from 49.2% to 60.8% in the MPSV4-primed group, and 79.3–93.1% in the MenACYW-TT-primed group. MenACYW-TT induced sufficient seroresponses in each primed group. Geometric mean titers (GMTs) for serogroups C, W, and Y remained or trended higher than pre-vaccination levels at both 3 and 6–7 years after primary vaccination, indicating immune persistence. Safety outcomes were comparable between groups. A MenACYW-TT booster was immunogenic and well tolerated in participants aged ≥59 years regardless of previous quadrivalent meningococcal vaccine received. The greatest immune responses occurred in those primed with MenACYW-TT.

123. The change of meningococcal carriage rate and serogroup among military trainees since the introduction of meningococcal vaccine, and the genetic characterization of the carriage isolates

Abstract Background Monovalent meningococcal conjugate vaccines against serogroups A or C have resulted in significant reduction of pharyngeal carriage rates against the vaccine serogroups. However, the effect of the quadrivalent meningococcal conjugate vaccine on meningococcal carriage has not yet been evaluated. Methods We assessed changes in pharyngeal carriage rates of Neisseria meningitidis after introduction of the quadrivalent meningococcal conjugate vaccine in Korean military trainees. Two rounds of oropharyngeal swabs of Korean military trainees were obtained, at the beginning and the end of the army training period. The first oropharyngeal swabs were collected prior to vaccination; the second round was performed 5 weeks later. Results In 2013, the overall N. meningitidis carriage rate was higher at the end of the training period (13.8%, 60 of 434 participants) than upon entry into military service (8.9%, 39 of 434 participants). Although the carriage rates of nongroupable and serogroup X isolates increased over the 5-week interval, carriage of the serogroup strains included in the quadrivalent meningococcal vaccine was reduced, from 7 to 2 isolates, after vaccination. However, in 2014, the overall carriage rate of N. meningitidis was significantly lower at the end of the training period (5.2%, 23 of 443 participants) than on entry into military service (12.6%, 56 of 443 participants) (p = 0.028). Carriage of vaccine serogroups isolates was significantly decreased, compared to that of non-vaccine serogroup B over the 5-week interval. Carriage isolates belonging to the ST-178, ST-31 and ST-41/44 were frequently identified clonal complex. Meningococcal carriage rate before and after Meningococcal vaccination in Korean military trainees Conclusion Meningococcal vaccination in Korean military trainees could lead to reduce pharyngeal carriage rates of vaccine serogroup meningococci. Therefore, the quadrivalent meningococcal conjugate vaccine is likely to prevent carriage acquisition of meningococci in closed populations such as military trainees. Disclosures All Authors: No reported disclosures.

Protocol of an Exploratory Single-Arm Study to Evaluate the Safety and Immunogenicity of KD-414 as a Booster Vaccine for SARS-CoV-2 in Healthy Adults (KAPIVARA).

Background: The coronavirus disease 2019 (COVID-19) pandemic is currently ongoing, and there have been significant efforts in the development of COVID-19 vaccines. However, the neutralizing antibody titers in vaccinated individuals are reported to progressively decrease over time. Japanese pharmaceutical companies have published the results of Phase I and II studies on the safety and efficacy of different vaccines. Final clinical trials will be conducted with the aim of practical application by March 2023. To effectively utilize vaccines developed by Japanese companies, the efficacy and safety of a booster dose (i.e., third vaccination) must be evaluated among individuals who have received three doses of different vaccines. Methods: This protocol describes a study that aims to examine the effect of a booster dose of “KD-414”, a novel Japanese inactivated vaccine, on antibody titers among participants involved in a previous study. Volunteers in this protocol will be recruited from participants in the previous study and immunized with KD-414 after obtaining consent. The antibody titers, before and after immunization with KD-414, among participants who previously received two doses of the BNT162b2 mRNA vaccine, will be comparatively analyzed. Discussion: The reactogenicity and immunogenicity of seven different COVID-19 vaccines including an inactivated vaccine as a third dose after two doses of ChAdOx1 nCov-19 or BNT162b2, has been tested previously, and found to be superior to control (quadrivalent meningococcal conjugate vaccine) regardless of which vaccine had been received during the initial course. This suggests that many types of third booster doses are efficacious. It is anticipated that this study will provide evidence of the safety and immunogenicity of KD-414 as a booster vaccine, which will have profound public health implications.

Factors associated with human papillomavirus and meningococcal vaccination among adolescents living in rural and urban areas

BackgroundStudies have shown that adolescent vaccination rates with human papillomavirus (HPV) and quadrivalent meningococcal conjugate (MenACWY) vaccines are lower in rural areas of the U.S. than in urban areas. We sought to determine factors associated with vaccine acceptance in these two settings. MethodsWe conducted a cross-sectional survey of 536 parents or guardians of teens age 13 through 15 years in select rural and urban counties of Minnesota and Wisconsin. We collected information on demographic variables, receipt of adolescent vaccines, and attitudes toward HPV vaccine in particular. Multivariable logistic regression models were used to assess associations between covariates and outcomes of interest (HPV vaccine receipt and MenACWY receipt). ResultsOf the 536 respondents, 267 (50%) resided in a rural county. Most respondents were female (78%) and non-Hispanic White (88%). About half (52%) of teens of the surveyed parents received the three vaccines recommended specifically for adolescents: 90% received tetanus-diphtheria-acellular pertussis (Tdap), 84% received MenACWY, and 60% received one or more doses of HPV vaccine. Rural and urban parents surveyed differed on several covariates relating to teen’s health services, parent’s demographics, and household characteristics. Parent’s perception of the importance that their healthcare providers placed on vaccination with HPV and MenACWY were independently associated with receipt of each of those vaccines (odds ratio [OR] 6.37, 95% confidence interval [CI] 2.90–13.96 and OR 2.15, 95% CI 1.07–4.31, respectively). Parents of vaccinated teens were less likely to report concerns about potential harm from the HPV vaccine or having heard stories about health problems caused by the HPV vaccine. ConclusionTeen receipt of HPV vaccine and MenACWY appears to be influenced by parents’ perception of vaccine importance, provider recommendations, and concerns regarding potential harm from the HPV vaccine. Continued education of providers and parents of the importance of adolescent vaccinations is warranted.

Frequency of vaccine-associated syncope after COVID-19 vaccination in adolescents.

Frequency of vaccine-associated syncope after COVID-19 vaccination in adolescents.

Comparing the meningococcal serogroup C immune response elicited by a tetanus toxoid conjugate quadrivalent meningococcal vaccine (MenACYW-TT) versus a quadrivalent or monovalent C tetanus toxoid conjugate meningococcal vaccine in healthy meningococcal vaccine-naïve toddlers: A randomised, controlled trial

ABSTRACT MenACYW-TT (MenQuadfi®) is a quadrivalent meningococcal tetanus toxoid conjugate vaccine licensed in Europe for use in individuals ≥12 months. This study assessed whether serogroup C immune responses with MenACYW-TT were at least non-inferior, or superior, to those of quadrivalent meningococcal ACWY (MCV4-TT; Nimenrix®) and monovalent meningococcal C (MenC-TT; NeisVac-C®) vaccines in toddlers (12–23 months). In this modified, double-blind Phase III study (NCT03890367), 701 toddlers received one dose of MenACYW-TT (n = 230), MCV4-TT (n = 232) or MenC-TT (n = 239). Serum bactericidal assays with human (hSBA) and baby rabbit (rSBA) complement were used to measure anti-meningococcal serogroup C antibodies at baseline and 30 days post-vaccination. A sequential statistical approach was used for primary and secondary objectives. For the primary objectives, superiority of serogroup C was assessed in terms of hSBA seroprotection rates (defined as titers ≥1:8) and GMTs for MenACYW-TT compared to MCV4-TT, and rSBA GMTs compared to MenC-TT. The safety of all vaccines within 30 days post-vaccination was described. When administered as a single dose to meningococcal vaccine-naïve healthy toddlers the superiority of the MenACYW-TT serogroup C immune response versus MCV4-TT was demonstrated for hSBA GMTs (ratio 16.3 [12.7–21.0]) and seroprotection (difference 10.43% [5.68–16.20]); and versus MenC-TT in terms of rSBA GMTs (ratio 1.32 [1.06–1.64]). The safety profiles of a single dose of MenACYW-TT, MCV4-TT and MenC-TT were similar. In meningococcal vaccine-naïve toddlers, MenACYW-TT induced superior immune responses to serogroup C versus MCV4-TT in terms of hSBA seroprotection and GMTs and versus MenC-TT in terms of rSBA GMTs.

Safety and immunogenicity of an investigational quadrivalent meningococcal tetanus toxoid conjugate vaccine (MenACYW-TT) co-administered with routine pediatric vaccines in infants and toddlers: A Phase II study

BackgroundThe MenACYW-TT conjugate vaccine is approved for prevention of invasive meningococcal disease (IMD) as a single dose in individuals ≥2 years of age in the United States and ≥12 months in EU and some other countries. This Phase II study evaluated the safety and immunogenicity of this vaccine and of concomitant pediatric vaccines in infants/toddlers (6 weeks–15 months of age). MethodsFive schedules of the MenACYW-TT conjugate vaccine were evaluated in the United States: 2, 4, 6, and 12 months; 2, 4, 6, and 15 months; 2, 4, and 12 months; 6 and 12 months; and 12 months alone. Routine pediatric vaccines (DTaP-IPV/Hib, PCV7/PCV13, MMR, and varicella) were administered per approved schedules. Proportions of participants with serum bactericidal antibodyassay with human complement (hSBA) titers ≥1:4 and ≥1:8, SBA with baby rabbit complement (rSBA) titers ≥1:8 and ≥1:128, and immune responses against concomitant vaccines were determined. ResultsTenderness and irritability were the most frequent solicited injection site and systemic reactions. Similar proportions of participants achieved an hSBA titer ≥1:8 for all four serogroups regardless of whether 2 or 3 doses were administered in the first year of life. Following a second-year dose, 91–100% of participants achieved the threshold for all 4 serogroups in all schedules regardless of the number of doses in the first year of life. Similar responses were seen with rSBA. Immunogenicity and safety profile of concomitant vaccines was similar whether the MenACYW-TT conjugate vaccine was administered or not. ConclusionMenACYW-TT conjugate vaccine administered with pediatric vaccines is safe and immunogenic regardless of the schedule and does not affect the immunogenicity or safety of the concomitant vaccines. Clinical trial registryNCT01049035.

A decade of data: Adolescent vaccination in the vaccine safety datalink, 2007 through 2016

BackgroundBetween May 2005 and March 2007, three vaccines were recommended by the Advisory Committee on Immunization Practices for routine use in adolescents in the United States: quadrivalent meningococcal conjugate vaccine (MenACWY), tetanus, diphtheria and acellular pertussis vaccine (Tdap), and human papillomavirus vaccine (HPV). Understanding historical adolescent vaccination patterns may inform future vaccination coverage efforts for these and emerging adolescent vaccines, including COVID-19 vaccines. MethodsThis was a descriptive, retrospective cohort study. All vaccines administered to adolescents aged 11 through 18 years in the Vaccine Safety Datalink population between January 1, 2007 and December 31, 2016 were examined. Vaccination coverage was assessed by study year for ≥1 dose Tdap or Td, ≥1 dose Tdap, ≥1 dose MenACWY, ≥1 dose HPV, and ≥3 dose HPV. The proportion of vaccine visits with concurrent vaccination (≥2 vaccines administered at the same visit) was calculated by sex and study year. The most common vaccine combinations administered in the study population were described by sex for two time periods: 2007–2010 and 2011–2016. ResultsThe number of 11–18-year-olds in the study population averaged 522,565 males and 503,112 females per study year. Between January 2007 and December 2016 there were 4,884,553 vaccine visits in this population (45% among males). The overall proportion of concurrent vaccine visits among males was 43% (33–61% by study year). Among females, 39% of all vaccine visits included concurrent vaccination (32–48% by study year). Vaccine coverage for Tdap, MenACWY, and 1- and 3-dose HPV increased across the study period. A wide variety of vaccine combinations were administered among both sexes and in both time periods. ConclusionsThe high vaccine uptake and multitude of vaccine combinations administered concurrently in the adolescent population of the Vaccine Safety Datalink provide historical patterns with which to compare future adolescent vaccination campaigns.