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JAMA Network Open Aug 2023
Topics: Humans; Gonorrhea; Incidence; Meningococcal Vaccines; Universities; Students
PubMed: 37651146
DOI: 10.1001/jamanetworkopen.2023.31742 -
The Lancet Regional Health. Europe Dec 2023Since the first emergence of Omicron BA.1 in England in November 2021, numerous sub-lineages have evolved. In September 2022, BA.5 dominated. The prevalence of BQ.1...
Vaccine effectiveness against hospitalisation estimated using a test-negative case-control study design, and comparative odds of hospital admission and severe outcomes with COVID-19 sub-lineages BQ.1, CH.1.1. and XBB.1.5 in England.
BACKGROUND
Since the first emergence of Omicron BA.1 in England in November 2021, numerous sub-lineages have evolved. In September 2022, BA.5 dominated. The prevalence of BQ.1 increased from October, while the prevalence of CH.1.1 and XBB.1.5 increased from December 2022 and January 2023, respectively. Little is known about the effectiveness of the vaccines against hospitalisation with these sub-lineages, nor the relative severity, so we here used national-level electronic health records from England to estimate vaccine effectiveness and variant severity.
METHODS
The study period for tests contributing to all analyses was from 5th December 2022 to 2nd April 2023, when the variants of interest were co-circulating. A test-negative case-control study was used to estimate the incremental effectiveness of the bivalent BA.1 booster vaccines against hospitalisation, relative to those with waned immunity where the last dose was at least 6 months prior. The odds of hospital admission for those testing PCR positive on the day of an attendance to accident and emergency departments and the odds of intensive care unit admission or death amongst COVID-19 admissions were compared between variants. Additionally, a Cox proportional hazards survival regression was used to investigate length of stay amongst hospitalised cases by variant.
FINDINGS
Our vaccine effectiveness study included 191,229 eligible tests with 1647 BQ.1 cases, 877 CH.1.1 cases, 1357 XBB.1.5 cases and 187,348 test negative controls. There was no difference in incremental vaccine effectiveness against hospitalisation with BQ.1, CH.1.1 or XBB.1.5, nor was there a difference in the severity of these variants. Effectiveness against hospitalisation was 48.0% (95% C.I.; 38.5-56.0%), 29.7% (95% C.I.; 7.5-46.6%) and 52.7% (95% C.I.; 24.6-70.4%) against BQ.1, CH.1.1 and XBB.1.5, respectively, at 5-9 weeks post booster vaccination. Compared to BQ.1, the odds of hospital admission were 0.87 (95% C.I.; 0.77-0.99) and 0.88 (95% C.I.; 0.75-1.02) for CH.1.1 and XBB.1.5 cases attending accident and emergency departments, respectively. There was no significant difference in the odds of admission to intensive care units or death for those with CH.1.1 (OR 0.96, 95% C.I.; 0.71-1.30) or XBB.1.5 (OR 0.67, 95% C.I.; 0.44-1.02) compared to BQ.1. There was also no significant difference in the length of hospital stay by variant.
INTERPRETATION
Together, these results provide reassuring evidence that the bivalent BA.1 booster vaccines provide similar protection against hospitalisation with BQ.1, CH.1.1 and XBB.1.5, and that the emergent CH.1.1 and XBB.1.5 sub-lineages do not cause more severe disease than BQ.1.
FUNDING
None.
PubMed: 38115965
DOI: 10.1016/j.lanepe.2023.100755 -
MMWR. Morbidity and Mortality Weekly... Aug 2023Three vaccines are routinely recommended for adolescents to prevent pertussis, meningococcal disease, and cancers caused by human papillomavirus (HPV). CDC analyzed data...
Three vaccines are routinely recommended for adolescents to prevent pertussis, meningococcal disease, and cancers caused by human papillomavirus (HPV). CDC analyzed data from the 2022 National Immunization Survey-Teen for 16,043 adolescents aged 13-17 years to assess vaccination coverage. Birth cohort analyses were conducted to assess trends in vaccination coverage by age 13 years (i.e., before the 13th birthday) and by age 14 years (i.e., before the 14th birthday) among adolescents who were due for routine vaccination before and during the COVID-19 pandemic. Cross-sectional analysis was used to assess coverage estimates among adolescents aged 13-17 years. In 2022, vaccination coverage by age 14 years among adolescents born in 2008 continued to lag that of earlier birth cohorts and varied by sociodemographic factors and access to health care compared with coverage among earlier birth cohorts. Vaccination coverage by age 13 years among adolescents born in 2009 was similar to coverage estimates obtained before the COVID-19 pandemic. Among all adolescents aged 13-17 years, 2022 vaccination coverage levels did not differ from 2021 levels; however, initiation of the HPV vaccination series decreased among those who were insured by Medicaid. Coverage with ≥1 dose of tetanus, diphtheria, and acellular pertussis vaccine and ≥1 dose meningococcal conjugate vaccine was high and stable (around 90%). Providers should review adolescent vaccination records, especially among those born in 2008 and those in populations eligible for the Vaccines for Children program, to ensure adolescents are up to date with all recommended vaccines.
Topics: United States; Child; Adolescent; Humans; Vaccination Coverage; Cross-Sectional Studies; Pandemics; Papillomavirus Infections; COVID-19; Vaccination; Immunization
PubMed: 37616185
DOI: 10.15585/mmwr.mm7234a3 -
Pediatric Research Sep 2023The immunogenicity and safety of a booster dose of tetanus toxoid-conjugate quadrivalent meningococcal vaccine (MenACYW-TT), alone or co-administered with MenB vaccine,... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The immunogenicity and safety of a booster dose of tetanus toxoid-conjugate quadrivalent meningococcal vaccine (MenACYW-TT), alone or co-administered with MenB vaccine, were assessed in healthy 13-25-year olds who received MenACYW-TT or a CRM-conjugate vaccine (MCV4-CRM) 3-6 years earlier.
METHODS
This phase IIIb open-label trial (NCT04084769) evaluated MenACYW-TT-primed participants, randomized to receive MenACYW-TT alone or with a MenB vaccine, and MCV4-CRM-primed participants who received MenACYW-TT alone. Functional antibodies against serogroups A, C, W and Y were measured using human complement serum bactericidal antibody assay (hSBA). The primary endpoint was vaccine seroresponse (post-vaccination titers ≥1:16 if pre-vaccination titers <1:8; or a ≥4-fold increase if pre-vaccination titers ≥1:8) 30 days post booster. Safety was evaluated throughout the study.
RESULTS
The persistence of the immune response following primary vaccination with MenACYW-TT was demonstrated. Seroresponse after MenACYW-TT booster was high regardless of priming vaccine (serogroup A: 94.8% vs 93.2%; C: 97.1% vs 98.9%; W: 97.7% vs 98.9%; and Y; 98.9% vs 100% for MenACWY-TT-primed and MCV4-CRM-primed groups, respectively). Co-administration with MenB vaccines did not affect MenACWY-TT immunogenicity. No vaccine-related serious adverse events were reported.
CONCLUSIONS
MenACYW-TT booster induced robust immunogenicity against all serogroups, regardless of the primary vaccine received, and had an acceptable safety profile.
IMPACT
A booster dose of MenACYW-TT induces robust immune responses in children and adolescents primed with MenACYW-TT or another MCV4 (MCV4-DT or MCV4-CRM), respectively. Here, we demonstrate that MenACYW-TT booster 3-6 years after primary vaccination induced robust immunogenicity against all serogroups, regardless of the priming vaccine (MenACWY-TT or MCV4-CRM), and was well tolerated. Persistence of the immune response following previous primary vaccination with MenACYW-TT was demonstrated. MenACYW-TT booster with MenB vaccine co-administration did not affect MenACWY-TT immunogenicity and was well tolerated. These findings will facilitate the provision of broader protection against IMD particularly in higher-risk groups such as adolescents.
Topics: Child; Humans; Adult; Adolescent; Tetanus Toxoid; Antibodies, Bacterial; Vaccination; Neisseria meningitidis; Meningococcal Vaccines; Vaccines, Conjugate
PubMed: 36899125
DOI: 10.1038/s41390-023-02478-5 -
BMC Microbiology Nov 2023Neisseria meningitidis can be carried asymptomatically in the human oropharynx without causing symptoms. Meningococcal carriage is relevant to the epidemiology of...
BACKGROUND
Neisseria meningitidis can be carried asymptomatically in the human oropharynx without causing symptoms. Meningococcal carriage is relevant to the epidemiology of invasive meningococcal disease (IMD). No carriage studies have been performed among the general population in Lithuania, whereas the incidence of IMD in Lithuania was among the highest in European countries from 2009 to 2019.
RESULTS
We analyzed a total of 401 oropharyngeal samples collected from university students from December 2021 to February 2023 for N. meningitidis carriage using direct swab PCR assays and culture. The overall carriage prevalence based on both or either swab PCR or culture was 4.99%. PCR-based assays were used to characterize 15 carriage isolates, including detection of genogroup, multilocus sequence typing profile, and typing of antigens PorA and FetA. The most common carriage isolates were capsule null locus (cnl), accounting for 46.7%, followed by genogroups B (26.7%) and Y (13.3%). We also performed a molecular characterization of invasive N. meningitidis isolates collected during the COVID-19 pandemic and post-pandemic period to understand better the meningococcal carriage in the context of prevailing invasive strains. Despite the substantial decrease in the incidence of IMD during the 2020-2022 period, clonal complex 32 (CC32) of serogroup B continued to be the most prevalent IMD-causing CC in Lithuania. However, CC32 was not detected among carriage isolates. The most common CCs were CC269, CC198, and CC1136. The antigen peptide variants found in most carried isolates were classified as 'insufficient data' according to the MenDeVAR Index to evaluate the potential coverage by the 4CMenB vaccine. Nearly half of the isolates were potentially covered by the Men-Fhbp vaccine. Resistance to ciprofloxacin was detected only for one cnl isolate. All isolates were susceptible to penicillin and ceftriaxone. Our analysis identified frequent partying (≥ 4 times/month) as a risk factor for meningococcal carriage, whereas smoking, living in a dormitory, and previous COVID-19 illness were not associated with the carriage.
CONCLUSIONS
Our study revealed a low prevalence of meningococcal carriage among university students in Lithuania. The carriage isolates showed genetic diversity, although almost half of them were identified as having a null capsule locus.
Topics: Male; Humans; Female; Neisseria meningitidis; Meningococcal Infections; Lithuania; Pandemics; Universities; Meningococcal Vaccines; Serogroup; Bacterial Vaccines; Students; Antigens, Bacterial
PubMed: 37978423
DOI: 10.1186/s12866-023-03111-5 -
The Journal of Infection Nov 2023In 2020, COVID-19 pandemic restrictions led to a major suppression of meningococcal disease in England. Here we describe the epidemiology of invasive meningococcal...
OBJECTIVES
In 2020, COVID-19 pandemic restrictions led to a major suppression of meningococcal disease in England. Here we describe the epidemiology of invasive meningococcal disease in the three years prior to the COVID-19 pandemic, and the three years immediately after the introduction of restrictions.
METHODS
The UK Health Security Agency conducts national meningococcal disease surveillance in England consisting of laboratory-based case confirmation with strain characterisation by culture and/or molecular detection, as well as clinical follow-up of all cases.
RESULTS
In the pre-pandemic period, 554-742 IMD cases were laboratory-confirmed per year. MenB caused 57.2% of cases, followed by MenW (22.7%), MenY (10.6%) and MenC (7.7%). The introduction of restrictions in late March 2020 led to a 73% reduction in IMD. After the removal of restrictions in 2021, a resurgence in MenB was observed, primarily in teenagers and young adults. During the following winter period (2022/23), MenB disease increased to the highest level since 2012 with cases rising across multiple age groups, however, cases in young children eligible for MenB vaccination remained lower than prior to the pandemic. MenACWY cases remained very low throughout the pandemic period.
CONCLUSIONS
Once pandemic restrictions in England were removed, MenB quickly rebounded- initially driven by a resurgence in teenagers/young adults, but later among other age groups. MenACWY cases remain very low due to the protection afforded by the adolescent MenACWY conjugate vaccine programme.
PubMed: 37689395
DOI: 10.1016/j.jinf.2023.09.002 -
Anales de Pediatria May 2024
Topics: Humans; Meningococcal Infections; Meningococcal Vaccines; Child; Healthcare Disparities
PubMed: 38582645
DOI: 10.1016/j.anpede.2024.03.023 -
MMWR. Morbidity and Mortality Weekly... Aug 2023On June 19, 2022, the original monovalent mRNA COVID-19 vaccines were approved as a primary series for children aged 6 months-4 years (Pfizer-BioNTech) and 6 months-5...
Effectiveness of Monovalent and Bivalent mRNA Vaccines in Preventing COVID-19-Associated Emergency Department and Urgent Care Encounters Among Children Aged 6 Months-5 Years - VISION Network, United States, July 2022-June 2023.
On June 19, 2022, the original monovalent mRNA COVID-19 vaccines were approved as a primary series for children aged 6 months-4 years (Pfizer-BioNTech) and 6 months-5 years (Moderna) based on safety, immunobridging, and limited efficacy data from clinical trials. On December 9, 2022, CDC expanded recommendations for use of updated bivalent vaccines to children aged ≥6 months. mRNA COVID-19 vaccine effectiveness (VE) against emergency department or urgent care (ED/UC) encounters was evaluated within the VISION Network during July 4, 2022-June 17, 2023, among children with COVID-19-like illness aged 6 months-5 years. Among children aged 6 months-5 years who received molecular SARS-CoV-2 testing during August 1, 2022-June 17, 2023, VE of 2 monovalent Moderna doses against ED/UC encounters was 29% (95% CI = 12%-42%) ≥14 days after dose 2 (median = 100 days after dose 2; IQR = 63-155 days). Among children aged 6 months-4 years with a COVID-19-like illness who received molecular testing during September 19, 2022-June 17, 2023, VE of 3 monovalent Pfizer-BioNTech doses was 43% (95% CI = 17%-61%) ≥14 days after dose 3 (median = 75 days after dose 3; IQR = 40-139 days). Effectiveness of ≥1 bivalent dose, comparing children with at least a complete primary series and ≥1 bivalent dose to unvaccinated children, irrespective of vaccine manufacturer, was 80% (95% CI = 42%-96%) among children aged 6 months-5 years a median of 58 days (IQR = 32-83 days) after the dose. All children should stay up to date with recommended COVID-19 vaccines, including initiation of COVID-19 vaccination immediately when they are eligible.
Topics: United States; Child; Humans; COVID-19; COVID-19 Vaccines; Vaccines, Combined; COVID-19 Testing; SARS-CoV-2; Emergency Service, Hospital; RNA, Messenger; mRNA Vaccines
PubMed: 37590187
DOI: 10.15585/mmwr.mm7233a2 -
MSphere Jun 2024serogroup B (NmB) strains have diverse antigens, necessitating methods for predicting meningococcal serogroup B (MenB) vaccine strain coverage. The genetic...
serogroup B (NmB) strains have diverse antigens, necessitating methods for predicting meningococcal serogroup B (MenB) vaccine strain coverage. The genetic Meningococcal Antigen Typing System (gMATS), a correlate of MATS estimates, predicts strain coverage by the 4-component MenB (4CMenB) vaccine in cultivable and non-cultivable NmB isolates. In Taiwan, 134 invasive, disease-causing NmB isolates were collected in 2003-2020 (23.1%, 4.5%, 5.2%, 29.8%, and 37.3% from individuals aged ≤11 months, 12-23 months, 2-4 years, 5-29 years, and ≥30 years, respectively). NmB isolates were characterized by whole-genome sequencing and vaccine antigen genotyping, and 4CMenB strain coverage was predicted using gMATS. Analysis of phylogenetic relationships with 502 global NmB genomes showed that most isolates belonged to three global hyperinvasive clonal complexes: ST-4821 (27.6%), ST-32 (23.9%), and ST-41/44 (14.9%). Predicted strain coverage by gMATS was 62.7%, with 27.6% isolates covered, 2.2% not covered, and 66.4% unpredictable by gMATS. Age group coverage point estimates ranged from 42.9% (2-4 years) to 66.1% (≤11 months). Antigen coverage estimates and percentages predicted as covered/not covered were highly variable, with higher estimates for isolates with one or more gMATS-positive antigens than for isolates positive for one 4CMenB antigen. In conclusion, this first study on NmB strain coverage by 4CMenB in Taiwan shows 62.7% coverage by gMATS, with predictable coverage for 29.8% of isolates. These could be underestimated since the gMATS calculation does not consider synergistic mechanisms associated with simultaneous antibody binding to multiple targets elicited by multicomponent vaccines or the contributions of minor outer membrane vesicle vaccine components.IMPORTANCEMeningococcal diseases, caused by the bacterium (meningococcus), include meningitis and septicemia. Although rare, invasive meningococcal disease is often severe and can be fatal. Nearly all cases are caused by six meningococcal serogroups (types), including meningococcal serogroup B. Vaccines are available against meningococcal serogroup B, but the antigens targeted by these vaccines have highly variable genetic features and expression levels, so the effectiveness of vaccination may vary depending on the strains circulating in particular countries. It is therefore important to test meningococcal serogroup B strains isolated from specific populations to estimate the percentage of bacterial strains that a vaccine can protect against (vaccine strain coverage). Meningococcal isolates were collected in Taiwan between 2003 and 2020, of which 134 were identified as serogroup B. We did further investigations on these isolates, including using a method (called gMATS) to predict vaccine strain coverage by the 4-component meningococcal serogroup B vaccine (4CMenB).
Topics: Humans; Taiwan; Meningococcal Vaccines; Neisseria meningitidis, Serogroup B; Infant; Child, Preschool; Child; Adult; Adolescent; Young Adult; Whole Genome Sequencing; Meningococcal Infections; Phylogeny; Antigens, Bacterial; Male; Female; Genotype; Vaccination Coverage
PubMed: 38752729
DOI: 10.1128/msphere.00220-24 -
NPJ Vaccines Feb 2024A decade ago, we described a new approach to discover next generation adjuvants, identifying small-molecule immune potentiators (SMIPs) as Toll-like receptor (TLR)7... (Review)
Review
A decade ago, we described a new approach to discover next generation adjuvants, identifying small-molecule immune potentiators (SMIPs) as Toll-like receptor (TLR)7 agonists. We also optimally formulated these drugs through adsorption to aluminum salts (alum), allowing them to be evaluated with a range of established and early-stage vaccines. Early proof-of-concept studies showed that a TLR7 agonist (TLR7a)-based SMIP, when adsorbed to alum, could perform as an effective adjuvant for a variety of different antigens, in both small and large animals. Studies in rodents demonstrated that the adjuvant enhanced immunogenicity of a recombinant protein-based vaccine against Staphylococcus aureus, and also showed potential to improve existing vaccines against pertussis or meningococcal infection. Extensive evaluations showed that the adjuvant was effective in non-human primates (NHPs), exploiting a mechanism of action that was consistent across the different animal models. The adjuvant formulation (named AS37) has now been advanced into clinical evaluation. A systems biology-based evaluation of the phase I clinical data with a meningococcal C conjugate vaccine showed that the AS37-adjuvanted formulation had an acceptable safety profile, was potent, and activated the expected immune pathways in humans, which was consistent with observations from the NHP studies. In the intervening decade, several alternative TLR7 agonists have also emerged and advanced into clinical development, such as the alum adsorbed TLR7/8 SMIP present in a widely distributed COVID-19 vaccine. This review summarizes the research and early development of the new adjuvant AS37, with an emphasis on the steps taken to allow its progression into clinical evaluations.
PubMed: 38332005
DOI: 10.1038/s41541-024-00810-6