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Department of Health SciencesUniversity of Florence
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strutture di Neisseria meningitidisSadarangani M & Pollard AJ. Lancet Infect Dis 2010; 10: 112-124
Department of Health SciencesUniversity of Florence
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A (α1 → 6)-linked - N-acetyl-D-mannosamina-1- fosfato
struttura
B (α2 → 8)-linked - N-acetil-l- acido neuroaminico
C (α2 → 9)-linked - N-acetil- acido neuraminico
sierogruppo
W135 (α2 → 6)-linked - 6-D-Gal (α1-4)-N-acido acetil-neuroaminico
Y (α2 → 6)-linked- 6-D-Glc (α1-4)-N-acido accetil-neuroaminico
struttura della capsula del meningococcoHill DJ et al. Clin Science 2010; 118: 547-564
Department of Health SciencesUniversity of Florence
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macroepidemiologia della malattia meningococcica Harrison LH et al. Vaccine 2009; 27:51-63
Department of Health SciencesUniversity of Florence
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stato di portatore per Neisseria meningitidis per etàChristensen H et al. Lancet Infect Dis. 2010;10:853-861.
Department of Health SciencesUniversity of Florence
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rischio [λs] di contrarre infezione grave da Neisseria meningitidis in fratelli di bambini che hanno precedentemente contratto l’infezioneHaralambous E et al. Epidemiol Infect 2003; 130: 413-418
λs complessivo:
λs legato al patogeno:
λs legato all’ospite:
30.3
18.4
11.9
casi attesi: 0.89
casi osservati: 27
promoter di TNF-αBaines PB & Hart CA. Brit J Anaesth 2003; 90: 72-83
IL-1Read RC et al. J Infect Dis 2000; 182: 1557-1560
IL-1RRead RC et al. J Infect Dis 2000; 182: 1557-1560
IN-1 dell’attivatore del plasminogenoHaralambous E et al. Crit Care Med 2003; 31: 2788-2793
FcgRIIγ ed FcgIIIγEmonts M et al. Lancet Infect Dis 2003; 3: 565-577
MBLEmonts M et al. Lancet Infect Dis 2003; 3: 565-577
promoter dell’esone 1 di MBL-2Garred P et al. Mol Immunol 2003; 40: 73-84
TLR4Smirnova I et al. PNAS 2003; 100: 6075-6080
properdina, C1q, C4, C2, fattore D, C5 → C9Kirschfink M & Mollnes T. Clin Diagn Lab Immunol 2003; 10: 982-989
fattori genetici implicati nello sviluppo e nel decorso di infezione da Neisseria meningitidis
Department of Health SciencesUniversity of Florence
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Department of Health SciencesUniversity of Florence
Neisseria meningitidis BVernikos G & Medini D. Path Glob Health 2014: 108: 305
incidenza fra le infezioni da Neisseriameningitidis:
Europa9 90 %Nuova Zelanda 82 %Australia 80 %Sud America 67 %Giappone 57 %Canada 53 %
- x17 il rischio nel lattante- 10 % di portatori- da 0 a 30 anni portatori in almeno 10 occasioni
SIMI ISS rapporto 2014: infezioni invasive da Neisseria meningitidis per sierogruppo [%] in Italia
2011 2012 2013
Neisseriameningitidis B 46 50 63
Neisseriameningitidis C 33 17 17
Neisseriameningitidis Y 16 17 13
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quanti sono realmente i casi di infezione meningococcica?
dati coltura SIMI – ISS
dati PCR [Prof C Azzari]
Department of Health SciencesUniversity of Florence
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meningite da meningococco C
SIMI: incidenza di meningite in Italia in bambini di età ≤ 4 anni negli anni 1994-2010
0
10
20
30
40
vaccino per meningococco C
meningite da meningococco B
Department of Health Sciences University of Florence
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età
epidemiologia per età della malattia meningococcica da Neisseria meningitidis B in Italia dal 2007 al 2013Azzari A et al. Vaccine 2013
Department of Health SciencesUniversity of Florence
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Department of Health SciencesUniversity of Florence
esito e sequele della malattia da Neisseria meningitidis in base al sierogruppo: review di 4 studiStein DM et al 2006; 24: 221 - 228
B [%] C [% ]
decesso 3.6 → 7.2 7.2 → 13.8
una qualunque sequela 4.8 → 10.2 7.9 → 15.3
sordità 1.9 → 3.2 1.9 → 3.8
amputazione 0.3 → 0.6 0 → 1.0
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Department of Sciences for Woman and Child's HealthUniversity of Florence
la malattia meningococcica, dopo la rabbia, è la condizione,fra quelle prevenibili con i vaccini, con il più elevato tasso di letalitàWHO report 2014
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Department of Health SciencesUniversity of Florence
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II
Vipond C et al. 2012; 305: 10-17
storia dei vaccini contro il meningococco
accineV
Department of Health Sciences University of Florence
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evaluation of a group B meningococcal N-propionylated polysaccharide conjugate vaccine in adult male volunteers: mean titres in ELISA units/mL of IgM specific for polysaccharidesBruge J et al. Vaccine 2004; 22: 1087-1096
immunogenicity of meningococcal B polysaccharide conjugated to tetanus toxoid or CRM197 via adipic dihydrazideBartoloni A et al. Vaccine 1995; 13: 463-470
Department of Health SciencesUniversity of Florence
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anticorpi vs Neisseria meningitisriconoscono le cellula del sistema nervoso centraleCoquillat D et al. Infect Immun 2001; 69: 7130-7139
l’epitopo riconosciuto da anticorpi vs meningococco B contiene residui N-acetiliciMoe GR et al. Infect Immun 2005; 69: 2123-2128
Department of Health SciencesUniversity of Florence
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phase I clinical trial with a hexavalent PorA containing meningococcal outer membrane vesicle vaccinePeeters CC et al. Vaccine 1996; 14: 1009-1015
broad vaccine coverage of a bivalent recombinaat factor H binding protein based vaccine to prevent serogroup B meningococcal vaccine
Jiang H-Q et al. Vaccine 2010; 28: 6086-6093
studies of outer membrane vesicle vaccine against Neisseria meningitidisLionel KK et al. N Engl J Med 2010; 362:1511-1520
immunogenicity of 2 serogroup outer-membrane protein meningococcal vaccines: a randomized controlled trial in ChileTappero JW et al. JAMA 1999; 281: 1520-1527
Department of Health SciencesUniversity of Florence
improvement of immunogenicity of meningococcal lipooligosaccharide by coformulation with lipidated transferrin-binding protein B in liposomes: implications for vaccine developmentMistretta N et al. Clin Vaccine Immunol 2012; 19: 711-722
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Department of Health SciencesUniversity of Florence
MenBvac: from B:15:P17,16 maningococcal strain MeNZB: from B:4:P1.7-2,4 meningococcal straingrown in a fermentor; extraction of OMVs with detergent deoxycholate
safety review: two outer membrane vesicle vaccines against Neisseria meningitidis BNøkleby H et al. Vaccine 2007; 25: 3080-3084
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adjuvant properties of meningococcal outer membrane vesicles and the use of adjuvants in Neisseria meningitidis protein vaccinesSanders H & Feavers IM. Expert Rev Vaccines 2011; 10: 323 - 334
Department of Health SciencesUniversity of Florence
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effectiveness of a vaccinationprogramme for an epidemic ofmeningococcal B in New ZealandArnold R et al. Vaccine 2011 29: 7100-7106
Department of Health SciencesUniversity of Florence
the vaccine containing outer membrane vesicles fromNeisseria meningitidis employedin New ZealandJohan Holst et al. Vaccine 2009;
the meningococcal B immunisation programme endedin June 2006, In that time, more than 1.1 million young New Zealanders received the MeNZB™ vaccine.about 80% of all under-20-year-olds have received three or more doses of MeNZB™.
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Department of Health SciencesUniversity of Florence
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Department of Health SciencesUniversity of Florence
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reverse vaccinology nel XXI secolo: implementazione oltre il disegno originaleDonati C & Rappuli R. Ann NY Acad Sciences, 2013
Department of Health SciencesUniversity of Florence
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proteina di fusione ricombinante Neisseria Heparin Binding Antigen (NHBA) di Neisseria meningitidis gruppo B 1, 2, 3 prodotta su cellule di Esherichia coli mediante tecnologia di DNA ricombinante 50 µg
proteina ricombinante Neisseria adhesin A (NadA) di Neisseria meningitidis B 1, 2, 3 prodotta su cellule di Esherichia coli mediante tecnologia di DNA ricombinante
50 µg
proteina di fusione ricombinante factor H binding protein (fHbp) di Neisseria meningitidis B 1, 2, 3 prodotta su cellule di Esherichia coli mediante tecnologia di DNA ricombinante
50 µg
vescicole della membrana esterna (OMV) di Neisseria meningitidis B ceppo NZ98/254 (quantità di proteina totale contenente PorA P1.4 2 ) ottenute con detergente da membrana di Neisseria meningitidis 25 µg
composizione del vaccino anti-meningococco B 4CMenB
adsorbito su idrossido di alluminio (0,5 mg Al3+)
eccipienti:- sodio cloruro - istidina - saccarosio - acqua per preparazioni iniettabili
Department of Health SciencesUniversity of Florence
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Department of Health SciencesUniversity of Florence
veicolo di proteine e lipidi con capacità modificare la risposta immune
vescicola
lume
outer membrane vesicles V NZ98/254
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1. incrementa la sopravvivenza batterica
2. anticorpi anti-NHBA sono presenti nel siero di pazienti sopravissuti a malattia da Neisseria meningitidis
3. anticorpi anti-NHBA sono protettivi
Neisseria Heparin Binding Antigen (NHBA; GNA2132) di Neisseria meningitidis Serruto D et al. PNAS 2010
intensità dello spot
sopravvissuti controlli
Department of Health SciencesUniversity of Florence
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Neisseria meningitidisNadAinvasina che promuove l’adesione batterica e la penetrazione nelle cellule epiteliali umane
Capecchi B et al. Molecular Microbiology 2006
Department of Health SciencesUniversity of Florence
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Department of Sciences for Woman and Child's HealthUniversity of Florence
il legame fra il fattore H ed il factor H binding protein (fHbp) di Neisseria meningitidis impedisce il contatto fra gli anticorpi specifici ed il batterio Granoff DM, Welsch JA, Ram S Infect Immun 2009; 77:764–769
fattore H
anticorpoanticorpoanticorpo
fattore H fattore H
anticorpo
Department of Health SciencesUniversity of Florence
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co-somministrabilità di 4CMenB con il vaccino esavalenteGossger N et al. JAMA 2012; 307: 573 - 582
Department of Health SciencesUniversity of Florence
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co-somministrabilità di 4CMenB con il vaccino anti-pneumococcicoGossger N et al. JAMA 2012; 307: 573 - 582
Department of Health SciencesUniversity of Florence
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fHbp NadA PorA 1.4 NHBA
dopo 4 dosi (2-4-6-12)
immunogenicità di 4CMenB nel lattante dopo 4 dosi a 2-4-6-12 mesiGossger N et al. JAMA 2012; 307: 573 - 582
dopo 3 dosi (2-4-6)
Department of Health SciencesUniversity of Florence
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persistenza di anticorpi battericidi successivamente alla vaccinazione nel lattante con vaccino contro il meningococco B ed immunogenicità di un richiamo in età prescolareSnape MD et al CMAJ 2014
Department of Health SciencesUniversity of Florence
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tollerabilità di 4CMenB nel lattanteGossger N et al. JAMA 2012; 307: 573 - 582
Department of Health SciencesUniversity of Florence
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condizione di portatore per 12 mesi a partire da tre mesi dopo la somministrazione del vaccino contro il meningococco B [4CMenB]Road R et al. Lancet 2014
acquisizione di maningococco per mese nei vaccinati
prevalenza dello stato di portatore nei non vaccinati
Department of Health SciencesUniversity of Florence
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Department of Health SciencesUniversity of Florence
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Department of Health SciencesUniversity of Florence
predizione valutata con metodica MATS della copertura di 4CMenBBorrow et al. IPNC 2012
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Department of Health SciencesUniversity of Florence
raccomandatoapprovato
offerta attiva e gratuita per i nuovi natiraccomandazione per categorie a rischio4CMenB: febbraio 2015
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Mese 3° 3°+15g 4° 4°+15g 5° 5°+15g 6° 7° 7°+15g 8° 9°Giorno 61° 76° 91° 106° 121° 136° 151° 181° 196° 221° 251°
Basilicata EsaPCV13
EsaPCV13
PugliaEsa
PCV13Esa
PCV13
ToscanaEsa
PCV13Esa
PCV13
LiguriaEsa
PCV13Esa
PCV13
SiciliaEsa
PCV13Esa
PCV13
VenetoFVG
Bolzano
EsaPCV13
EsaPCV13
prima dose seconda dose terza dose
4CMenB: inserimento nei calendari regionali del ciclo primario
4CMenB4CMenB
4CMenB
4CMenB
4CMenB
4CMenB
4CMenB
4CMenB
4CMenB 4CMenB
4CMenB
4CMenB
4CMenB
4CMenB
4CMenB 4CMenB
Department of Health Sciences University of Florence
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Department of Health SciencesUniversity of Florence
piano vaccini 2015
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Proposta MenB Calendario per la Vita
40
http://www.societaitalianaigiene.org/site/new/images/docs/calendariovaccinale/2013/cvplv.pdf
Ultimo accesso in data 20 Gennaio 2015
Department of Health SciencesUniversity of Florence
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Department of Health SciencesUniversity of Florence
dosi 4CMenB secondo scheda tecnica
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Morley SL, Pollard AJ
Department of Paediatrics, Imperial College School of Medicine, St Mary's Campus, Norfolk Place, London
vaccine prevention of meningococcal disease, coming soon?Vaccine 2001; 12: 666-687
Sadarangani M & Pollard AJ
Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford
serogroup B meningococcal vaccines: an unfinished storyLancet Infect Dis 2010;10: 112-124
Department of Health SciencesUniversity of Florence
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Department of Health SciencesUniversity of Florence