Meningococcal Vaccines: Current Status and Emerging Strategies

McCarthy, Pumtiwitt C.; Sharyan, Abeer; Moghaddam, Laleh Sheikhi

doi:10.20944/preprints201801.0291.v1

Cited by 17 publications

(13 citation statements)

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“…Furthermore, Nme sequester the complement regulator fH via the outer membrane proteins fHbp [5] and NspA [6]. Both, capsule and fHbp are used as antigens in meningococcal vaccines [7,8].…”

Section: Introductionmentioning

confidence: 99%

Distinct roles of the anaphylatoxin receptors C3aR, C5aR1 and C5aR2 in experimental meningococcal infections

et al. 2019

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The complement system is pivotal in the defense against invasive disease caused by Neisseria meningitidis (Nme, meningococcus), particularly via the membrane attack complex. Complement activation liberates the anaphylatoxins C3a and C5a, which activate three distinct G-protein coupled receptors, C3aR, C5aR1 and C5aR2 (anaphylatoxin receptors, ATRs). We recently discovered that C5aR1 exacerbates the course of the disease, revealing a downside of complement in Nme sepsis. Here, we compared the roles of all three ATRs during mouse nasal colonization, intraperitoneal infection and human whole blood infection with Nme. Deficiency of complement or ATRs did not alter nasal colonization, but significantly affected invasive disease: Compared to WT mice, the disease was aggravated in C3ar −/mice, whereas C5ar1 −/and C5ar2 −/mice showed increased resistance to meningococcal sepsis. Surprisingly, deletion of either of the ATRs resulted in lower cytokine/chemokine responses, irrespective of the different susceptibilities of the mice. This was similar in ex vivo human whole blood infection using ATR inhibitors. Neutrophil responses to Nme were reduced in C5ar1 −/mouse blood. Upon stimulation with C5a plus Nme, mouse macrophages displayed reduced phosphorylation of ERK1/2, when C5aR1 or C5aR2 were ablated or inhibited, suggesting that both C5a-receptors prime an initial macrophage response to Nme. Finally, in vivo blockade of C5aR1 alone (PMX205) or along with C5aR2 (A8 Δ71−73) resulted in ameliorated disease, whereas neither antagonizing C3aR (SB290157) nor its activation with a "super-agonist" peptide (WWGKKYRASKLGLAR) demonstrated a benefit. Thus, C5aR1 and C5aR2 augment disease pathology and are interesting targets for treatment, whereas C3aR is protective in experimental meningococcal sepsis.

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“…Furthermore, Nme sequester the complement regulator fH via the outer membrane proteins fHbp [5] and NspA [6]. Both, capsule and fHbp are used as antigens in meningococcal vaccines [7,8].…”

Section: Introductionmentioning

confidence: 99%

Distinct roles of the anaphylatoxin receptors C3aR, C5aR1 and C5aR2 in experimental meningococcal infections

et al. 2019

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“…138 They are immunogenic in children and adults, elicit immunological memory, and eliminate the carrier status, thereby making them suitable for population-scale interventions. 139 Monovalent conjugate serogroup C and A, and quadrivalent conjugate meningococcal vaccines have been licensed to date, to our knowledge. 139 The last addition to the vaccine armamentarium against meningococcus is the multicomponent serogroup B meningococcal vaccine, which is immuno genic and safe in children (older than 2 months), adolescents, and adults (no data for people older than 50 years).…”

Section: From Passive Serum Therapy To Active Immunisationmentioning

confidence: 99%

“…139 Monovalent conjugate serogroup C and A, and quadrivalent conjugate meningococcal vaccines have been licensed to date, to our knowledge. 139 The last addition to the vaccine armamentarium against meningococcus is the multicomponent serogroup B meningococcal vaccine, which is immuno genic and safe in children (older than 2 months), adolescents, and adults (no data for people older than 50 years). 140 Results from clinical trials 141 suggest that serogroup B meningococcal vaccine, like the other conjugate vaccines, might lead to herd immunity, reducing not only carriage of the serogroup included in the vaccine but also of other serogroups.…”

Section: From Passive Serum Therapy To Active Immunisationmentioning

confidence: 99%

Standing on the shoulders of giants: two centuries of struggle against meningococcal disease

Domingo

Pomar

Mauri

et al. 2019

The Lancet Infectious Diseases

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Meningococcal disease was first clinically characterised by Gaspard Vieusseux in 1805, and its causative agent was identified by Anton Weichselbaum in 1887, who named it Diplococcus intracellularis menigitidis. From the beginning, the disease was dreaded because of its epidemic nature, predilection for previously healthy children and adolescents, and high mortality. In the last decade of the 19th century, the concept of serum therapy for toxin-related bacterial diseases was identified. This concept was applied to meningococcal disease therapy, in an independent way, by Wilhelm Kolle, August von Wasserman, and Georg Jochmann in Germany, and Simon Flexner in the USA, resulting in the first successful approach for the treatment of meningococcal disease. During the first three decades of the 20th century, serum therapy was the standard treatment for meningococcal disease. With the advent of sulphamides first and then antibiotics, serum therapy was abandoned. The great challenges that infectious diseases medicine is facing and the awaiting menaces in the future in terms of increasing antibiotic resistance, emergence of new pathogens, and re-emergence of old ones without effective therapy, make passive immunotherapy a promising tool. Acknowledging the achievements of our predecessors might teach us some lessons to bring light to our future. e285 www.thelancet.com/infection Vol

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“…Consequently, monovalent MenC conjugate vaccines (MCCV) were developed by multiple manufacturers and these were subsequently introduced across Europe and globally [5]. Three monovalent MCCV were licensed, two vaccines used CRM-197 as carrier protein and one used Tetanus toxoid (TT), which have been followed by three quadrivalent ACWY meningococcal conjugate vaccines (MCV4), each conjugating either CRM-197 or TT or diphtheria toxoid (DT), a monovalent meningococcal A conjugate vaccine conjugating to TT and two combination meningococcal conjugate vaccines, a Hib-MenC conjugate vaccine and a Hib-MenCY conjugate vaccine, both conjugating to TT [6]. The United Kingdom (UK) was the first country to incorporate MCCV into the routine immunization schedule in 1999, closely followed by several other countries [7][8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Systematic literature review of the impact and effectiveness of monovalent meningococcal C conjugated vaccines when used in routine immunization programs

Htar

Jackson²,

Balmer

et al. 2020

BMC Public Health

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Background Monovalent meningococcal C conjugate vaccine (MCCV) was introduced into the routine immunization program in many countries in Europe and worldwide following the emergence of meningococcal serogroup C (MenC) in the late 1990s. This systematic literature review summarizes the immediate and long-term impact and effectiveness of the different MCCV vaccination schedules and strategies employed. Methods We conducted a systematic literature search for peer-reviewed, scientific publications in the databases of MEDLINE (via PubMed), LILACS, and SCIELO. We included studies from countries where MCCV have been introduced in routine vaccination programs and studies providing the impact and effectiveness of MCCV published between 1st January 2001 and 31st October 2017. Results Forty studies were included in the review; 30 studies reporting impact and 17 reporting effectiveness covering 9 countries (UK, Spain, Italy, Canada, Brazil, Australia, Belgium, Germany and the Netherlands). Following MCCV introduction, significant and immediate reduction of MenC incidence was consistently observed in vaccine eligible ages in all countries with high vaccine uptake. The reduction in non-vaccine eligible ages (especially population > 65 years) through herd protection was generally observed 3–4 years following introduction. Vaccine effectiveness (VE) was mostly assessed through screening methods and ranged from 38 to 100%. The VE was generally highest during the first year after vaccination and waned over time. The VE was better maintained in countries employing catch-up campaigns in older children and adolescents, compared to routine infant only schedules. Conclusions MCCV were highly effective, showing a substantial and sustained decrease in MenC invasive meningococcal disease. The epidemiology of meningococcal disease is in constant transition, and some vaccination programs now include adolescents and higher valent vaccines due to the recent increase in cases caused by serogroups not covered by MCCV. Continuous monitoring of meningococcal disease is essential to understand disease evolution in the setting of different vaccination programs.

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Meningococcal Vaccines: Current Status and Emerging Strategies

Cited by 17 publications

References 0 publications

Distinct roles of the anaphylatoxin receptors C3aR, C5aR1 and C5aR2 in experimental meningococcal infections

Distinct roles of the anaphylatoxin receptors C3aR, C5aR1 and C5aR2 in experimental meningococcal infections

Standing on the shoulders of giants: two centuries of struggle against meningococcal disease

Systematic literature review of the impact and effectiveness of monovalent meningococcal C conjugated vaccines when used in routine immunization programs

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