Uso dei vaccini nell’adulto

Istituto di Malattie Infettive e Tropicali Università degli Studi di Brescia

VII° Congresso Nazionale SIMITBergamo, 19 –22 Novembre 2008

Giampiero Carosi

Vaccine role in the health of nations

• Immunisation and provision of clean water are, among all public health interventions, those with the greatest impact on world’s health

• Vaccines are among the most cost-effective health interventions available

World Health Organisation

World Bank

Goal of vaccine interventions in infants and children

Vaccines are often such a powerful tool that they can make elimination of a specific disease an achievable target.

The required components of an effective recepy are:

- High effectiveness- Extensive coverage- Herd immunity effect

Herd immunity

• Successful vaccination protects immunised individuals from infection, thereby decreasing the percentage of susceptible persons within a population and reducing the possibility of infection transmission to others.

• At a definable prevalence of immunity, an infectious organism can no longer circulate freely among the remaining susceptibles

Smallpox: the only example of a successful eradication campaign

(May 8th, 1980)

Other intermediate effects

On the way of elimination, vaccines may deeply change the clinical history of a medical condition by decreasing the incidence of a specific agent or shifting the epidemiologic pattern of an infection from epidemic to endemic

Notified bacterial meningitis cases, Italy 1994 - 2008

Source: Sistema di Sorveglianza meningiti batteriche SIMI-ISS

050

100150200250300350400450

PneumoMeningoHib

Hib conjugate vaccine

This vaccine both elicits durable immunity by the time maternal-derived antibodies dissipate, and reduces nasopharyngeal carriage thus diminishing the risk of transmission

Just by chance ?

Effective vaccines are not available for:– AIDS – tuberculosis – malaria

the biggest health problems that we are facing today

Factors causing decreased acceptability of vaccines

• Awareness of disease threats is decreasing (as a consequence of vaccine efficacy !!!!): measles, polio, etc.

• Some segments of the public are unwilling to accept any risk of vaccine associated vaccination…. missing the need to make cost-benefit balances

Vaccines are under attack as a cause of neurodevelopmental disorders, autoimune disorders, etc.

CDC’s review of VAERS reports CDC’s review of VAERS reports concerning Gardasil:concerning Gardasil:

• As at June 30 2008, 9749 reports of adverse events after Gardasil administration over an estimate of at least 8 million women receiving the vaccine.

• 93% non serious: syncope, pain at the injection site, headcahe, nausea, and fever. Risk of fainting added to Gardasil prescribing information

• 7% serious: death, Guillain-Barré syndrome (GBS) and thromboembolic disorders.

CDC’s review of VAERS:CDC’s review of VAERS:Gardasil and GBSGardasil and GBS

• According to CDC and FDA analysis no evidence that Gardasil vaccinated women have an increase of the baseline 1 to 2 per 100,000 incidence of GBS in the general population

• No changes to any of the existing HPV recommendations • Close to publication the data of the Vaccine Safety Datalink

(VSD) project comparing a vaccinated (> 300,000 doses) and an unvaccinated population on the risk of 9 specific important outcomes including GBS

Polio vaccination in Italy

• Polio 1,2,3 live attenuated vaccine (OPV, Sabin) more immunogenic than inactivated vaccine (IPV, Salk) but rarely associated with polio-like disease

• After polio eradication in Italy, based on a risk / benefit analysis, IPV replaced OPV for infant and adult vaccination

Adult immunization strategies

• Rather than elimination, the aim is the reduction of morbidity/mortality in specific population groups– Increased risk of morbidity

• Influenza, invasive pneumococcal disease for the elderly

• Cervical cancer in women

– Increased exposure• Vaccine preventable diseases in travellers

• Influenza among health staff, etc.

Summary (1)

• Vaccines have a great potential among public heath prevention strategies

• Demonstrated remarkable achievements at very attractive costs

• The development of vaccines for the major endemic infectious diseases are a priority for current and future research

Professor zur Hausen, Nobel Prize winner in Medicine 2008 for his research on HPV

GLO

BO

CA

N 2

002

< < 91.591.5< < 15.415.4

< < 33.233.2< < 9.79.7

< < 25.325.3

BREASTBREAST

CERVIX UTERICERVIX UTERI

COLON/RECTUMCOLON/RECTUM

LUNGLUNG

STOMACHSTOMACH

470.606

445.963

337.115

317.883

1.050.346

Life time risk Life time risk 3-4%3-4%

ESTIMATES OF THE WORLDWIDE ESTIMATES OF THE WORLDWIDE INCIDENCE OF CERVICAL CANCERINCIDENCE OF CERVICAL CANCER

La superficie esterna del virus è costituita da due proteine capsulari: L1 and L2

Il capsomero è costituito da 72pentameri, ciascuno formato da 5 molecole di L1

1 molecola di L2 è incastonata nella cavità centrale del pentamero

Gli anticorpi neutralizzanti riconoscono epitopi conformazionali di L1

Non sono noti in natura anticorpi neutralizzanti diretti verso L2

La struttura del virus

La protezione è associata alla produzione di anticorpi neutralizzanti1

Anticorpi neutralizzanti prevengono l’infezione

da HPV

Anticorpi non neutralizzanti non

prevengono l’infezione da HPV

Infezione – assenza di anticorpi

1. Chen XS, Garcea RL, Goldberg I, et al. Molecular Cell. 2000;5:557–567.

Recettore cellulare

Vaccini basati su VLPs

• Aventis Pasteur MSD / Merck vaccino quadrivalente per tipi

6, 11 (condilomatosi) e 16, 18 (carcinoma della cervice)

• Manifattura delle VLPs in S. cerevisiae

• Adiuvante

– Alluminio idrossifosfato solfato amorfo (AAHS)

Vaccini basati su VLPs

• GSK vaccino bivalente per tipi 16, 18 (carcinoma della cervice)

• Manifattura delle VLPs su colture cellulari di insetti infettate da baculovirus

• Adiuvante– Idrossido d’alluminio +

3-O-deacilato-monofosforil lipide A (AS04)

0

4000

8000

12000

16000

day 60 day 210

HPV16

pre0

1000

2000

3000

day 60 day 210

HPV18

pre

= [Al(OH)3]= AS04

Median

Median

Q3

Q1

Q3

Q1

3.6 x*

2.2 x

Fre

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i cel

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B a

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Vaccino GSK anti HPV formulato con AS04 induce cellule

B di memoria anti-HPV 16/18 specifiche

* statistically significant (p <0.05, Wilcoxon’s test)

vaccinazione vaccinazione

Giannini SL, et al. Vaccine 2006; 24: 5937–49

L’adiuvante AS04. Cellule B di memoria

Determinants for the cost-effectiveness analysis of HPV vaccines

• Protective efficacy: virtually 100% on TARGET TYPES and provided that HAD NOT OCCURRED prior to vaccination

• Health benefits: delayed impact on cervical cancer, early impact on cervical dysplasia and genital warts

• Cost of the vaccine

• Duration of protection

Risposta B memory e durata della protezione vaccinica

• Dose booster a 60 mesi dopo ciclo iniziale:– 1 settimana dopo il re-challenge titoli anticorpali

simili 1 mese post primo ciclo– Sierotitoli più elevati 1 mese dopo il rechallenge

rispetto ad 1 mese post primo ciclo

Efficacia vaccinica duratura, forse life-long

Olsson SE, Vaccine 2007, 25: 4931 - 4939

ColonizationColonization

Crossing of mucosal barrierCrossing of mucosal barrier

Otitis media, sinusitis,

nonbacteremic pneumonia

Otitis media, sinusitis,

nonbacteremic pneumonia

Local invasionLocal invasion

Pneumococcal Disease: Pathogenesis

Meningitis Sepsis

Meningitis Sepsis

Invasion of bloodstreamInvasion of bloodstream

Bacteremic

pneumonia

Bacteremic

pneumonia

SOGGETTI >65 anni

SOGGETTI 2-64 anni

Condizioni ambientali

Disordini immunitari

Asplenia/Splenectomia

Emopatie (anemia a cellule falciformi/talassemia)

Immunodeficit congeniti/acquisiti

Patologie croniche

BPCO/CARDIOPATIE

Diabete mellito

Epatopatie/Nefropatie

Malformazioni

Traumi cranici con fistole

23 valente

SOGGETTI <2 anniSOGGETTI <2 anni

SOGGETTI 2-5 anniSOGGETTI 2-5 anni

Disordini immunitariDisordini immunitari

Asplenia/SplenectomiaAsplenia/Splenectomia

Emopatie Emopatie (anemia a cellule (anemia a cellule falciformi/talassemia) falciformi/talassemia)

Immunodeficit congeniti/acquisitiImmunodeficit congeniti/acquisiti

MalformazioniMalformazioni

Traumi cranici con fistoleTraumi cranici con fistole

Patologie “croniche”Patologie “croniche”

CARDIOPATIECARDIOPATIE

Diabete mellitoDiabete mellito

Epatopatie/NefropatieEpatopatie/Nefropatie

7 7 valentevalente

Indicazioni attuali vaccino antipneumococcico in Italia

Conjugated and un-conjugated pneumococcal vaccines

• Conjugated vaccines (but not polisaccharide vaccines) induce mucosal immunity.

• These vaccines are effective in reducing bacterial colonisation and carrier state

• They exert a significant herd immunity effect which is not demonstrated for polisaccharide vaccines

Nurkka A et al., 2001

81

63

27

9,4 4,8 2,50

20

40

60

80

100

1998/99 2000 2001 2002 2003 2004

Cases p

er

100,0

00

Reduction of invasive pneumococcal disease in <5 children

CDC unpublished data and MMWR Sep 16, 2005

97% reduction

0

10

20

30

40

50

60

70

1998 1999 2000 2001 2002 2003 2004

Year

Incid

ence /

100,0

00

PCV7 introduction

>80 y

65-79 y

50-64 y

18-49 y

% Change 2003/4 vs 98/99>80: -77% (-82,-71)65-79: -74% (-79,-67)50-64: -64% (-70,-57)18-49: -76% (-80,-72)

Moore et. al. 2006 ICEID

Reduction of invasive pneumococcal disease in unvaccinated adults

Vaccine introduced

0

20

40

60

80

100

120

140

160

1996 1997 1998 1999 2000 2001 2002 2003 2004

Inci

den

ce (

case

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er 1

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Penicillina-resistenti

Penicillina sensibili

Kyaw, M. H. et al. N Engl J Med 2006;354:1455-1463

Riduzione delle patologie invasive da pneumococco resistenti alla pennicillina in bambini sotto i 2 anni

Vaccino antipneumococcico e obiettivi di salute in Italia

• Obiettivo: ridurre morbidità da malattia pneumococcica nei < 5 anni

• Stimando incidenza 60 / 100k, efficacia 90%, copertura 90%, share tipi vaccinali 80% prevenzione 900 casi / anno

• Efficacia certa, ma costo-efficacia diversamente valutata dalle regioni (alti costi attuali del vaccino - attuale difficoltà in misurare morbidità)

Summary (2)

• Adult vaccination strategies aim at morbidity reduction rather than disease elimination

• Vaccine targets are derived by a thourough comprehension of disease impact in specific population groups

• The benefits of several effective adult vaccines (including HPV, pneumococcus, etc.) might be better exploited

Il vaccino per l’influenza stagionale

Il Ministero della Salute sulla base dell’evidenza che la vaccinazione antiinfluenzale riduce la malattia in soggetti sani adulti del 70 – 90% e la mortalità per influenza nell’anziano del 40 – 75%, raccomanda la vaccinazione a:

• persone con età maggiore di 64 anni• bambini di età > 6 mesi con comorbidità • bambini in trattamento cronico con ASA• adulti affetti da patologie croniche• donne che saranno in 2-3 trimestre di gravidanza all’epoca del picco

epidemico• ospiti di lungodegenze• personale sanitario• persone a contatto con soggetti ad alto rischio di complicanze• soggetti addetti a mansioni pubbliche di primario interesse• soggetti a contatto con animali potenzialmente affetti da ceppi aviari

Ministero della Salute: “Prevenzione e controllo dell’influenza: raccomandazioni per la stagione 2006-07”

Target di copertura vaccinale in Italia

Target minimo 70%, ottimale 100%

Ministero della Salute: “Prevenzione e controllo dell’influenza: raccomandazioni per la stagione 2006-07”

Copertura vaccinale effettiva in Italia

60% in anziani, adulti con co-morbidità 1.4% personale sanitario 8.2%, addetti a servizi di primario interesse 2.5%

Piano Nazionale Vaccini 2003-2005Ministero della Salute: “Prevenzione e controllo dell’influenza: raccomandazioni per la stagione 2006-07”

.

Preparedness for the influenza pandemic

• Drugs

– antivirals

– othres (antibiotics)

• Vaccines

– pandemic

– Pre-pandemic

• Social distancing

Global plan

Influenza vaccines• Vaccines are the mainstay for prevention of seasonal flu

since half a century

• A pandemic vaccine will be developed, but impact on the pandemic low because of delayed availability

• Pre-pandemic vaccines developed to gain time. New adjuvants and new production techniques been developed (antigen sparing). Assumptions– Low efficacy ~30% (mismatch, one dose)

– New adjuvants allow broaden efficacy on drifted strains

– Priming may be done with one or two doses

Development of the vaccine strategy

PANDEMIC VACCINE

1^ DOSE

2^ DOSE

1^ DOSE

3^ DOSE

2^ DOSE PROTECTION

DECLARATION OF PANDEMIC

PROTECTION

PROTECTION

PRE-PANDEMIC VACCINE

2^ DOSE

1^ DOSE

Case fatality rate

> 60% in human cases of avian influenza

2% in 1918 pandemic

0.2% in 1957 pandemic

< 0.1% in seasonal flu

Ruolo del vaccino nel piano pandemico italiano

Nella fase 3, caratterizzata da presenza di un nuovo sottotipo virale, ma assenza di trasmissione interumana, è necessario identificare le categorie prioritarie a cui offrire la vaccinazione pandemica. Il presente Piano identifica 6 categorie, elencate in ordine di priorità:1. Personale sanitario e di assistenza (ospedali, …)2. Personale addetto ai servizi essenziali alla sicurezza e alla emergenza (polizia, …)3. Personale addetto ai servizi di pubblica utilità (esercito….)4. Persone ad elevato rischio di complicanze severe o fatali a causa dell’influenza5. Bambini e adolescenti sani di età compresa tra 2 e 18 anni6. Adulti sani

Ministero della Salute. Piano nazionale di preparazione e risposta ad unapandemia influenzale. 2006

Pandemic severity index

CDC 2007: available at www.pandemicflu.gov

Summary (4)

• We keep on waiting the next influenza pandemic

• Models predict that its severity might be substantial, and, mostly, unpredictable beforehand

• A comprehensive vaccination strategy, which include the use of seasonal influenza, pre-pandemic and pandemic vaccines, will be a mainstay of health system response.

1) Routine immunizations (measles, polio, dT, influenza, etc.)

2) Routine travel immunizations (Hep. A, typhoid, etc.)

3) Host country required immunizations (yellow fever)

4) Geographic risk immunizations (JE, meningococcus, TBE, etc.)

5) Extended stay immunizations (Hep B, rabies, etc)

6) Which vaccination for which traveller?

7) When are you leaving? Tomorrow …

8) Vaccine/drugs interactions

Immunization of theInternational Traveler

Immunization of theInternational Traveler

Thanassi e Weiss, 1997; 43-70

1) Ruotine immunizationupdated?

yes

No (update)

2) Routine Travelimmunization updated?

yes 3) Host countryrequirements?

yes

4) Geographic riskupdated?yes

5) Extended stayimmunization updated?

yesREADYTO GO!

No (update)

No (update)

No (update)No (update)

Booster of tetanus vaccine in adults

1 dose IM (0.5 mL – 40 IU)

Diphteria-tetanus vaccines dTDiphteria 2 IU (instead of 30)To avoid local and rare systemic adverse events

Incidence of Hep A100 times that of Typhoid1000 times that of cholera

Hepatitis A: vaccine characteristicsHepatitis A: vaccine characteristics

Very well tolerated Immunogenic: 58% at w2, 97% at w4

Vaccinate 4 wks before departure

TwinrixTM Update

• Hepatitis A Inactivated & Hepatitis B (Recombinant) Vaccine

• Accelerated dosing schedule of 0, 7, 21-30 days and a booster dose at 12 months

• FDA approved March 28, 2007

Yellow fever in travellersYellow fever in travellers

8 cases reported in 8 cases reported in travellers in 1970-2002travellers in 1970-2002

- all to remote areas- all to remote areas- many with short stay- many with short stay- no history of epidemic- no history of epidemic- 6/8 died- 6/8 died- 7/8 not vaccinated - 7/8 not vaccinated

Incidence of Yellow feverIncidence of Yellow fever

True incidence ~ 200,000 cases / year (underreporting)True incidence ~ 200,000 cases / year (underreporting)

Risk in unvaccinated traveller / month of stayRisk in unvaccinated traveller / month of staydisease:disease: 1: 4,0001: 4,000death:death: 1: 20,0001: 20,000

10 times higher in Africa compared10 times higher in Africa compared to South Americato South America

Severe adverse reactions to YF vaccineSevere adverse reactions to YF vaccine

• Hypersensitivity reactionsHypersensitivity reactions• Encephalitis (viral)Encephalitis (viral)• Liver failure and MOF (viral)Liver failure and MOF (viral)

10 cases recently described10 cases recently described8 fatal8 fatalsuspected rate of 1:400,000suspected rate of 1:400,000(compare to polio: 1:750,000)(compare to polio: 1:750,000)

Vaccinate persons who are truly exposed !Vaccinate persons who are truly exposed !

Riemergenza del colera confermata nel 2006236.896 casi in 52 Paesi6311 casi mortaliTasso di letalità del 2,66%Incremento globale del 79% in rapporto ai casisegnalati nel 2005

Colera: rischio elevato in caso di epidemie

20052005

Il vaccino WC/rBS (whole cell-recombinant B-subunit) ha individuato come strategia quella di indurre la produzione di anticorpi contro:- il corpo batterico- la subunità B della tossina colerica con l’obiettivo di bloccare il suo attacco alle cellule intestinali e, quindi, alla subunità A (parte attiva della tossina) di rendersi intracellulare ed esplicare la propria azione patogena

Vaccino WC/rBSVaccino WC/rBS

ImmunizzazioneImmunizzazione

Similitudine antigenica tra le subunità B delle tossine di Vibrio cholerae e di Escherichia coli

enterotossigena (ETEC),

Vaccino WC/rBSVaccino WC/rBS

Incidenza complessiva della diarrea nei viaggiatori

Vaccinati = 23%

Non vaccinati = 40%

P = 0.004

Incidenza della diarrea nei viaggiatori in Africa (<21 gg)

Vaccinati = 16%

Non vaccinati = 48% P = 0.002

Incidenza della diarrea nei viaggiatori in India e Sud est Asiatico (<21 gg)

Vaccinati = 19 %

Non vaccinati = 50% P = 0.052

Efficacia del vaccino anticolerico orale WC/rBS nella prevenzione della TD

Riduzione del rischio del 43% (R. Lopez-Gigosos, TMID,june 2007)(R. Lopez-Gigosos, TMID,june 2007)

Risk of meningococcal meningitis in travellers

Where: the meningitis belt in AfricaPilgrimage areas

Risk for travellers: 0.4 / 1,000,000Risk for pilgrims: 2,000 / 1,000,000

Meningococcal conjugate polysaccharide vaccine

Chemical conjugation to a protein carrier monovalent (C) in Italy quadrivalent (A+C+Y+W-135) in US

In Italy: Age: > 12 months 1 dose, intramuscolarDuration of protection: unknown (no clear boosting

requirements defined)

What vaccine for international travellers ?

Priority should be given to the need to protect from all potential meningococcal strains

Quadrivalent polysaccharide

Who needs meningococcal vaccine ?

• Hajj visa requirement for all pilgrims

• Travellers to the African meningitis belt during December – June.

• Extend to other geographical areas and time periods according to epidemic warnings

• Recommandation strenghthened for health care workers, long stay, prolonged contact with local populations

Is vaccination effective ?

Since the introduction of the quadrivalent meningococcal (A, C, Y, W135) vaccine as Hajj visa requirement in the year 2002, no further outbreaks have occurred.

Wilder-Smith A, Emerg Infect Dis 2003; 9:734–7.

Summary (3)

• Vaccines are a mainstay of travel medicine preventive interventions

• The selection of vaccine recommandations is based on destination as well as traveller characteristics

• Research for the development of vaccines for malaria and dengue are the first priorities in this area

CD

C. M

MW

R

2005

;54

BACK - UPBACK - UP

MMWR 2008; 57: 893

Indicazioni all’impiego di BCGIndicazioni all’impiego di BCG

….La vaccinazione antitubercolare e' inoltre

consigliata per neonati e bambini di età inferiore a

5 anni, con test TST negativo, che siano esposti

ad un elevato rischio di acquisizione dell’infezione

ad esempio che viaggino verso paesi ad alta

endemia per un periodo superiore a 6 mesi.

Progetto di aggiornamento delle raccomandazioni per le attività di controllo della tubercolosiCCM - 2008

MMWR 2008; 57: 893

Meccanismi proposti per la risposta immune ad HPV1–5

1. Stanley M. Vaccine. 2005 [Epub ahead of print]. 2. Batista FD, Neuberger MS. EMBO Journal. 2000;19:513–520. 3. Tyring SK. Curr Ther Res. 2000;61:584–596. 4. Roden RB, Hubbert NL, Kirnbauer R, et al. J Virol. 1996;70:3298–3301. 5. Chen XS, Garcea RL, Goldberg I, et al. MolCell. 2000;5:557–567.

La risposta B memory

• Importanza della risposta B memory:– Permette una risposta vigorosa se re-challenge

dell’antigene– Permette una risposta molto più rapida che nel corso

del challenge iniziale

Extending recommandations for HPV vaccines

• Ongoig trials will soon shed light on efficacy and safety among:– Women 26 to 54 years of age– Boys and men

• The true challenge will be to extend the coverage among pre-adolescent girls

Vaccinazione per S.pneumoniae in Italia

• Vaccino glico-coniugato eptavalente• Registrato in Italia nel 2001• 81% dei casi di meningite in Italia imputabile a

ceppi vaccinali (dati ISS)• Incluso nel calendario vaccinazione solo per

bambini a rischio di età < 5 anni• Tre dosi nel primo anno di vita (immunogeno

nell’infanzia, a differenza di 23-valente)

Statements: Efficacia

5) Studi clinici controllati presenti in letteratura hanno messo in evidenza elevati livelli di efficacia del vaccino eptavalente coniugato nei confronti delle infezioni invasive classiche da pneumococco (meningite, sepsi, batteriemia occulta), risultati buoni nelle polmoniti di comunità (batteriemiche e non) e discreti nelle otiti medie acute IA

Italian Consensus Workshop on conjugated pneumococcal vaccines (2007)

7) Le valutazioni dell’incidenza della patologia pneumococcica prima e dopo l’introduzione della vaccinazione universale dei nuovi nati hanno confermato l’efficacia della vaccinazione nel ridurre la patologia pneumococcica sia nei soggetti vaccinati (effetto diretto) sia nella popolazione non vaccinata di tutte le età (effetto indiretto). IA

Statements Efficacia

Italian Consensus Workshop on conjugated pneumococcal vaccines (2007)

Politiche regionali sul vaccino antipneumococcico

• Offerta gratuita a tutti < 5 anni ad alto rischio

• Disponibilità vaccino gratuito o a spesa compartecipata sulla base delle strategie regionali

10% 10,000

1% 1,000

0,1% 100

100%

Traveller’s diarrhoea

100,000Any health problem: used medication or felt ill

Felt subjectively ill

MalariaConsulted doctor abroad or back home

Stayed in bed

Incapacity of work after returnAcute febrile respiratory tract infections

Hospitalized abroad Hepatitis AGonorrhoea

Hepatitis B Air evacuation

Typhoid (India, N, NW-Africa)

0,01% 10Died abroad (PVC) HIV-infection

Legionellosis Typhoid (other areas)

0,001% 1 Poliomyelitis, asymptomatic

Cholera 0,0005% Paralytic poliomyelitis 0,00007

Died abroad (any traveller)

MORBIDITY AND MORTALITY IN TRAVELLERS TO DEVELOPING CONTRIES: INCIDENCE RATES PER MONTH OF STAY ABROAD

Steffen Manson’s p 407

1) Routine immunizations

• poliomielitis• diphteria• tetanus• pertussis• HBV

• Haemophilus b• measles• rubella• mumps

Hepatitis A: vaccine characteristicsHepatitis A: vaccine characteristics

Inactivated, whole cell vaccineTwo doses, 0 – 6/12 mtsProtection lasts for ….?

The vaccine has replaced immunoglobulins (except for very last minute travel and children < 2 yrs)

Yellow Fever: the vaccine

CONTROINDICATION: children below the age of 6 monthspregnantpersons allergic to eggsimmunosuppressed

Vaccination valid for 10 years

Immunogenic: 90% after 10 dd - 99% after 30 ddProtectivew capacity: > 95%

ADVERSE REACTIONS: ?

17D strain of attenuated yellow fever virus - 0,5 mL - single dose17D strain of attenuated yellow fever virus - 0,5 mL - single dose

Caratteristiche dei vaccini anticolerici (Castelli et all., 2004)

Tipo di vaccino parenterale CVD 103 HgR WC/rBs

Somministrazione parenterale orale Orale

N° dosi 2 1 2-3

Efficacia protettiva 30-50% 62-100% 85-90% (6 mesi)

Biotipo classico El Tor

Durata protettiva 3 mesi 6 mesi 63%

(3 anni) (> 5 anni)

Efficacia anti ETEC NO NO SI (52%)

Tollerabilità Effetti locali Sicuro, lievi disturbi

gastrointestinali

Sicuro, lievi disturbi

gastroenterici

Parenterale: a cellule intere, inattivatoCVD 103 HgR: vivo attenuato, V. cholerae 01 geneticamento deletodella subunità AWC/rBs: a cellule intere, inattivato V cholerae 01 con subunità B ricombinante

Meningococcal polysaccharide vaccines

Purified capsular polysaccharide monovalent (A, C) and bivalent (A/C) quadrivalent (A+C+Y+W-135)

1 dose, subcutaneousAge: > 2 yearsDuration of protection: 3 years

A substantial proportion of cases are caused by “type B” meningococcus, for which no vaccine is licensed or available

Advantages of conjugate vaccines

Usefulness of the Polysaccharide vaccine is limited because it does not confer long-lasting immunity and does not cause a sustainable reduction of nasopharyngeal carriage of N. meningitidis, and therefore does not interrupt transmission sufficiently to elicit herd immunity.Conjugate vaccines exert enhanced immunogenicity due to the protein component, which elicit a T-cell dependant antibody response:

immunogenic in infants longer duration of protection reduction of nasopharyngeal carriage

Vaccino pandemico e prepandemicoVaccino pandemico• Poiché il tipo virale della prossima pandemia è attualmente ignoto, il vaccino

pandemico attualmente non esiste. Tuttavia, sono in atto procedure accelerate per rendere la preparazione, sperimentazione, registrazione e disseminazione del vaccino la più rapida possibile dopo l’insorgenza della prossima pandemia.

Vaccino pre-pandemico• Vi sono indizi che il prossimo ceppo pandemico sia un ceppo aviario H5 (più

probabilmente) oppure H7 o H9. Sulla base di questa previsione sono in fase avanzata di registrazione vaccini diretti verso i corrispettivi virus aviari, definiti vaccini pre-pandemici.

Vaccino per l’influenza stagionale• La vaccinazione per l’influenza stagionale può conferire una sorta di priming

che renda la vaccinazione pandemica più efficace una volta disponibile.

Pre-pandemic vaccines

• Pre-pandemic vaccines need strategies for:– Priming of the population– Stock-piling

What will determine the priority governments will give to the

pandemic response ?