Pediatric Invasive Meningococcal Disease, Auckland, New Zealand (Aotearoa), 2004–2020

Burton, Cameron; Best, Emma; Broom, Matthew; Heffernan, Helen; Briggs, Simon; Webb, Rachel

doi:10.3201/eid2904.221397

Cited by 3 publications

(4 citation statements)

References 30 publications

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“…The OMV vaccine was tested in several clinical trials where it showed an acceptable safety profile and a strong immune response after three doses of the vaccine. The vaccination program was staggered throughout the different regions of New Zealand, delivered to different age groups at a time between 2004 and 2006, and used for infant routine vaccination until 2008 [ 45 ]. The vaccine was estimated to be 77% effective and prevented an estimated 210 cases of MenB IMD with its attendant sequelae between July 2004 and December 2008 [ 46 ].…”

Section: Licensed Outer Membrane Vesicle (Omv)-based Vaccinesmentioning

confidence: 99%

Outer Membrane Vesicle Vaccine Platforms

Micoli,

Adamo,

Nakakana

2023

BioDrugs

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Outer membrane vesicles (OMVs) are spontaneously released by many gram-negative bacteria during their growth and constitute an important virulence factor for bacteria, helping them to survive through harsh environmental conditions. Native OMVs, naturally-released from bacteria, are produced at a level too low for vaccine manufacturing, requiring chemical treatment (detergent-extracted) or genetic manipulation, resulting in generalized modules for membrane antigens (GMMAs). Over the years, the nature and properties of OMVs have made them a viable platform for vaccine development. There are a few licensed OMV vaccines mainly for the prevention of meningitis caused by Neisseria meningitidis serogroup B (MenB) and Haemophilus influenzae type b (Hib). There are several candidates in clinical development against other gram-negative organisms from which the OMVs are derived, but also against heterologous targets in which the OMVs are used as carriers (e.g. coronavirus disease 2019 [COVID-19]). The use of OMVs for targets other than those from which they are derived is a major advancement in OMV technology, improving its versatility by being able to deliver protein or polysaccharide antigens. Other advances include the range of genetic modifications that can be made to improve their safety, reduce reactogenicity, and increase immunogenicity and protective efficacy. However, significant challenges remain, such as identification of general tools for high-content surface expression of heterologous proteins on the OMV surface. Here, we outline the progress of OMV vaccines to date, particularly discussing licensed OMV-based vaccines and candidates in clinical development. Recent trends in preclinical research are described, mainly focused on genetic manipulation and chemical conjugation for the use of OMVs as carriers for heterologous protein and polysaccharide antigens. Remaining challenges with the use of OMVs and directions for future research are also discussed.

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Section: Licensed Outer Membrane Vesicle (Omv)-based Vaccinesmentioning

confidence: 99%

Outer Membrane Vesicle Vaccine Platforms

Micoli,

Adamo,

Nakakana

2023

BioDrugs

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“…New Zealand has relatively high rates of invasive meningococcal disease. It has been estimated that New Zealand has an incidence over 2-fold higher than that of other high-income countries [10,11]. Māori and Pacifika communities are disproportionately affected by the disease, along with people living in deprivation [10,12].…”

Section: List Of Figuresmentioning

confidence: 99%

“…It has been estimated that New Zealand has an incidence over 2-fold higher than that of other high-income countries [10,11]. Māori and Pacifika communities are disproportionately affected by the disease, along with people living in deprivation [10,12]. This disparity is predicted to increase further with rising poverty and socioeconomic inequity in New Zealand [10].…”

Section: List Of Figuresmentioning

confidence: 99%

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Genomic Organisation of Meningococcal pilS in Carriage and Disease

Gea

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<p><strong>Neisseria meningitidis (meningococcus) is an obligate human pathogen that can cause invasive meningococcal disease. Meningococci asymptomatically colonise the nasopharyngeal mucosa as commensals in up to 30% of the population. Disease occurs when the bacteria adhere to epithelial cells and invade deeper tissues, rapidly replicating in the bloodstream or crossing the blood-brain barrier. This is a severe disease with serious long term sequelae. Vaccines have been developed against the capsule surrounding the bacteria and other recombinant proteins, but despite this, rates of invasive meningococcal disease are still high. The vaccines are not as effective against carriage and the pathogenesis of the bacterium is still poorly understood. The type IV meningococcal pilus is a known virulence factor that facilitates adhesion to different cell types. The pilus is made up of repeating subunits of the PilE protein, encoded by the pilE gene. This gene undergoes extensive recombination with a genomic locus called pilS. However, due to the long and repetitive nature of the pilS region, previous studies using short-read sequencing have been unable to accurately resolve this region. The overarching goal of this project was to use long read sequencing to resolve the pilS region and compare the genomic structure of this region between closely related carriage and disease isolates. These isolates were taken during the New Zealand meningococcal disease epidemic from 1991-2008. Isolates were taken from the index disease patient and their healthy household contacts. Healthy household contacts were often found to be asymptomatically carrying N. meningitidis of the same sequence type as the index disease patient. These carriage and disease pairs are indistinguishable by common laboratory typing, however a previous study showed the carriage isolates from one household had a truncated pilS compared to the disease isolate [1]. The aim was to look for consistent differences in the pilS region between closely related carriage and disease isolates. Long read Oxford Nanopore sequencing was used to generate assemblies for each of the isolates that mapped across repetitive regions. A method to annotate the highly repetitive pilS region was developed, including the promoter sequence and cis regulatory elements. Bioinformatic pipelines were developed to compare the pilS region between carriage and disease isolates. The variation in the expressed pilE gene was also investigated, showing conserved and highly variable regions, which corroborates what has been described in the literature. In this work, the genomes of 23 N. meningitidis isolates have been sequenced and assembled. The pilS region of all the isolates has been annotated. No consistent differences in pilS were found between carriage and disease isolates. However, by using Oxford Nanopore sequencing, novel deletions have been detected in the pilS region that have not been described in the literature. These deletions have been validated bioinformatically and experimentally by isolating and sequencing single colonies of N. meningitidis. A bioinformatic pipeline has been developed to use Oxford Nanopore sequencing to identify regions of high variation, which can be applied to other recombinant genomic loci. Understanding the genomic variation of the pilS region is important to understanding how the pilus contributes to invasive meningococcal disease.</strong></p>

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Invasive Meningococcal Disease in North Batina, Oman in 2023. A Case Study

Al Maqbali,

Al Hashmi,

Al Saadi

et al. 2024

ejmhr

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Invasive Meningococcal Disease is a severe bacterial infection with a high fatality rate particularly in young children. It is caused by Neisseria meningitidis bacteria which colonizes the nasopharynx. The transmission is by direct contact with droplets or discharge from an infected person or a carrier. Invasive meningococcal disease commonly presents as meningitis or meningococcemia. Acute meningococcemia progresses rapidly with a characteristic purpuric rash. Confirmation of the disease is through isolating the bacteria from sterile body fluids (CSF, blood). Early diagnosis and treatment are crucial. Recognizing purpuric rash as a late symptom of meningococcemia is important. Vaccination remains remains the best prevention. In this case study we present the details of a 12-year-old Omani child with rapidly progressive fulminant meningococcemia, leading to death.

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Pediatric Invasive Meningococcal Disease, Auckland, New Zealand (Aotearoa), 2004–2020

Cited by 3 publications

References 30 publications

Outer Membrane Vesicle Vaccine Platforms

Outer Membrane Vesicle Vaccine Platforms

Genomic Organisation of Meningococcal pilS in Carriage and Disease

Invasive Meningococcal Disease in North Batina, Oman in 2023. A Case Study

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