Quadrivalent meningococcal (MenACWY-TT) conjugate vaccine or a fourth dose of H. influenzae–N. meningitidis C/Y conjugate vaccine (HibMenCY-TT) is immunogenic in toddlers who previously received three doses of HibMenCY-TT in infancy

BackgroundImmunogenicity and safety of a single dose of MenACWY-TT or a fourth dose of HibMenCY-TT were evaluated in the second year of life in HibMenCY-TT-primed toddlers.MethodsHealthy infants were randomized (5:1) and primed at 2, 4 and 6 months of age with HibMenCY-TT and diphtheria–tetanus–acellular pertussis–hepatitis B-inactivated poliovirus (DTaP–HBV–IPV) vaccine; or Hib-TT and DTaP–HBV–IPV (control). Recipients of HibMenCY-TT + DTaP–HBV–IPV were re-randomized (2:2:1) to receive MenACWY-TT at 12–15 months and DTaP at 15–18 months; MenACWY-TT co-administered with DTaP at 15–18 months; or HibMenCY-TT at 12–15 months and DTaP at 15–18 months. Controls received DTaP only at 15–18 months due to Hib conjugate vaccine shortage. Serum bactericidal activity using human complement (hSBA) and safety were assessed one month after meningococcal vaccination.ResultsAfter vaccination with MenACWY-TT at 12–15 months or MenACWY-TT + DTaP at 15–18 months, all subjects previously primed for serogroups C/Y had hSBA ≥1:8 for these serogroups. At least 96.1% also had hSBA ≥1:8 for serogroups A/W. All subjects in the HibMenCY-TT group had hSBA ≥1:8 for serogroups C/Y. All pre-defined statistical criteria for meningococcal immunogenicity were satisfied. All vaccination regimens had acceptable safety profiles.ConclusionChildren primed with three doses of HibMenCY-TT who then received a single dose of MenACWY-TT or a fourth dose of HibMenCY-TT had robust increases in hSBA titers for serogroups C/Y. These data provide support that MenACWY-TT, given with or without the fourth scheduled dose of DTaP could be administered as an alternative to a fourth dose of HibMenCY-TT in the second year of life.This study (110870/110871) is registered at www.clinicaltrials.gov NCT00614614.     

Surveillance of invasive meningococcal disease in the Tel Aviv District,Israel, 2007–2017

Invasive meningococcal disease (IMD) is one of the leading causes of bacterial meningitis and septicemia in Israel. The purpose of the study was to describe the IMD in the Tel Aviv District and to identify specific populations who could benefit from vaccine introduction.In the Tel Aviv District, the incidence rates ranged from 0.4 to 1.4 cases per 100,000 population per year during 2007–2017.During the study period, seventy-nine patients (65%) occurred among children younger than four years of age. Eight deaths occurred (7%), most of them among children under the age of 1 year (5 deaths; 15%). A serogroup was identified in 82 isolates. Most of the isolates (69 cases − 84%) belonged to serogroup B (NmB).IMD clustered geographically in the city of Bnei Brak, with a predominantly Ultra-Orthodox Jewish population. It is the youngest and most densely populated city in the district. The overall incidence rates of IMD among children in Bnei Brak were more than seven times higher in children up to nine years, compared to the rest of the district. Specifically for NmB, disease rates were 9.08 times higher in children up to the age of four, and 7.74 times higher in children from five to nine years old in Bnei Brak, compared to the rest of the district.Our findings describe the burden of a vaccine-preventable disease and reinforce the need for routine 4CmenB introduction, especially in groups where the disease clusters.     

Vaccines against Neisseria meningitidis serogroup B strains – What does genomics reveal on the Portuguese strain’s coverage

In Portugal, Neisseria meningitidis serogroup B (MenB) is the most common serogroup causing invasive meningococcal disease. To protect against MenB disease two protein based MenB vaccines are available in Portugal, the 4CMenB that was licenced in 2014 and included in the routine immunization program in October 2020, and the bivalent rLP2086 vaccine licensed in 2017. The aim of this study was to predict the coverage of the 4CMenB and rLP2086 vaccines against Portuguese isolates of Neisseria meningitidis sampled between 2012 and 2019 and to evaluate the diversity of vaccine antigens based on genomic analysis.Whole-genome sequence data from 324 Portuguese Neisseria meningitidis isolates were analysed. To predict strain coverage by 4CMenB and rLP2086, vaccine antigen reactivity was assessed using the MenDeVar index available on the PubMLST Neisseria website.This study included 235 (75.6%) MenB isolates of all invasive MenB strains reported between 2012 and 2019. Moreover, 89 non MenB isolates sampled in the same period, enrolling 68 from invasive disease and 21 from healthy carriers, were also studied.The predicted strain coverage of MenB isolates was 73.5% (95% CI: 64.8%–81.2%) for 4CMenB and 100% for rLP2086. Predicted strain coverage by 4CMenB in the age group from 0 to 4 years old, was 73.9%. Most of MenB isolates were covered by a single antigen (85.4%), namely fHbp (30.3%), P1.4 (29.2%), and NHBA (24.7%).In Portugal, the most prevalent peptides in MenB isolates were: P1.4 (16.2%), NHBA peptide 2 (14.0%), and fHbp peptide 14 (7.2%), from 4CMenB and fHbp peptide 19 (10.6%) from rLP2086. No significant temporal trends were observed concerning the distribution and diversity of vaccine antigen variants.4CMenB and rLP2086 vaccines showed potential coverage for isolates regardless serogroup.The use of both vaccines should be considered to control possible outbreaks caused by serogroups with no vaccine available.     

A dose-range study assessing immunogenicity and safety of one dose of a new candidate meningococcal serogroups A,C, W-135, Y tetanus toxoid conjugate (MenACWY-TT) vaccine administered in the second year of life and in young children

Meningococcal disease incidence is highest in young children, yet a tetravalent conjugate vaccine is currently not available for this age group. This study evaluated a single dose of four different ACWY-TT conjugate vaccine formulations in 240 toddlers (12–14 months) and 268 children (3–5 years) compared to licensed age-appropriate control vaccines. In toddlers, rSBA-MenC GMTs for the selected formulation were statistically higher than after monovalent-MenC-conjugate vaccine. In children, rSBA-GMTs against each serogroup were statistically higher than after tetravalent polysaccharide vaccine. The safety profile was comparable to licensed controls. The new ACWY-TT conjugate vaccine promises high seroprotection levels against meningococcal disease from 1 year of age.     

2003年成都市流脑免疫状况调查

目的了解成都市2岁以上人群流脑免疫状况,2～15岁人群对A C群流脑多糖疫苗接种的免疫反应。方法对成都市2～5、6～9、12～15、20～40岁4个年龄组,每组随机抽取不少于30人,采集血清;采用ELISA法检测人群及免疫者血清中的A群和C群流脑抗体,并进行统计分析。结果A群抗体GMT及阳性率为1∶5.76、69.05%,C群抗体GMT及阳性率为1∶1.94、25.36%。A C群流脑多糖疫苗免疫后1个月,A群抗体GMT及阳性率上升为1∶15.10、100.00%,免疫成功率为52.78%,C群抗体GMT及阳性率上升为1∶18.57、97.92%。C群免疫成功率为79.86%。结论成都市健康人群的A群抗体水平高于C群,A C群流脑多糖疫苗的C群免疫抗体水平增长幅度高于A群。     

Tetravalent meningococcal serogroups A, C, W-135 and Y conjugate vaccine is well tolerated and immunogenic when co-administered with measles-mumps-rubella-varicella vaccine during the second year of life: An open, randomized controlled trial

Co-administration of meningococcal ACWY-tetanus toxoid conjugate vaccine (ACWY-TT) with MMRV vaccine was investigated in 1000 12-23-month old children randomized (3:3:1:1) to receive co-administered ACWY-TT + MMRV, or a single dose of ACWY-TT, MMRV or MenC-CRM₁₉₇. Non-inferiority of ACWY-TT to MenC-CRM₁₉₇ and non-inferiority of ACWY-TT + MMRV to ACWY-TT and MMRV alone, and the immunogenicity of serogroups AWY were demonstrated according to pre-defined criteria. Fever reactions in ACWY + MMRV and MMRV groups were comparable. ACWY-TT can be co-administered with MMRV without affecting immunogenicity or safety profiles of either vaccine.This study has been registered at www.clinicaltrials.gov NCT00474266.     

The immunogenicity and safety of a tetravalent measles-mumps-rubella-varicella vaccine when co-administered with conjugated meningococcal C vaccine to healthy children: A phase IIIb,randomized, multi-center study in Italy

IntroductionMultiple vaccination visits and administrations can be stressful for infants, parents and healthcare providers. Multivalent combination vaccines can deliver the required number of antigens in fewer injections and clinic visits, while vaccine co-administration can also reduce the number of visits. This non-inferiority study was undertaken to evaluate the feasibility of co-administering a combined measles-mumps-rubella-varicella (MMRV) vaccine with conjugated meningococcal C (MenC) vaccine in a large cohort of healthy Italian toddlers.MethodsHealthy subjects aged 13–15 months were randomized (2:1:1) to receive single doses of either: co-administered MMRV + MenC at the same visit (MMRV + MenC group); or MMRV followed 42 days later by MenC (MMRV group); or MenC followed 42 days later by MMRV (MenC group). Blood samples were collected before and 43 days after vaccination. Antibody titers against MMRV were measured using ELISA. Functional-anti-meningococcal-serogroup activity (rSBAMenC) was assessed using a serum bactericidal test. Solicited local and general reactions were recorded for up to 4 and 42 days post-vaccination, respectively. Non-inferiority of MMRV + MenC to MMRV (post-dose-1 seroconversion rates) and MMRV + MenC to MenC (post-dose-1 seroprotection rates) was achieved if the lower limit (LL) of the 95% confidence interval (CI) for the group difference was ⩾−10% for each antigen.Results716 subjects were enrolled in the study. At 42 days post-vaccination, the MMRV seroconversion rates were 99.3% (measles), 94.5% (mumps), 100% (rubella) and 99.7% (varicella) in the MMRV + MenC group, and 99.4%, 93.2%, 100% and 100%, respectively, in the MMRV group. The seroprotection rates against rSBA-MenC were 98.3% in the MMRV + MenC group and 99.3% in the MenC group. Non-inferiority was reached for all the vaccine antigens. The safety profiles were as expected for these vaccines.ConclusionThe immune responses elicited by co-administered MMRV + MenC were non-inferior to those elicited by MMRV or MenC alone and support vaccination of children with both vaccines at a single visit.Clinical Trials registration: NCT01506193.     

Dynamic changes in clinical characteristics and serotype distribution of invasive pneumococcal disease among adults in Japan after introduction of the pediatric 13-valent pneumococcal conjugate vaccine in 2013–2019

Nationwide population-based surveillance for invasive pneumococcal disease (IPD) is being conducted in few Asian countries. We aimed to evaluate the clinical characteristics and serotype distribution among Japanese adult patients with IPD after introduction of the pediatric 13-valent pneumococcal conjugate vaccine (PCV13) in 2013. IPD surveillance was conducted among adults between 2013 and 2019, and 1,995 patients were analyzed by time period (early, 2013–2015; middle, 2016–2017; late, 2018–2019). We found that the period of 2018–2019 was independently associated with a lower risk of fatal outcome, compared with the period of 2013–2015. The proportion of those with serotype PCV13-nonPCV7 decreased significantly in patients aged 15–64 years and in those aged ≥ 65 years within 3 years after the introduction of pediatric PCV13. By contrast, the proportion of those with nonvaccine serotype increased significantly in those aged ≥ 65 years, but not in those aged 15–64 years. No significant change was found in the proportion of 23-valent polysaccharide pneumococcal vaccine (PPSV23)-nonPCV13 in both of adults aged 15–64 years and ≥ 65 years. The proportions of PCV15-, PCV20- and PCV24-covered serotypes were 38%, 56% and 58% in adult patients with IPD aged ≥ 65 years during the late period. Our data on the serotype distribution support an indirect effect from pediatric PCV13 use among adults, and afford a basis for estimates of protection against IPD by vaccination with newly developed PCVs in older adults in Japan.