Prevention of Meningococcal Disease

Marco Aurélio P. Sáfadi, MD, PhDFCM da Santa Casa de São Paulo

Neisseria meningitidis

• Polysaccharide capsule (12 serogroups) A, B, C, Y, X and W….

• Genetic characterization (DNA sequencing of 7 housekeeping genes - MLST)

• Whole genome phylogenetic analyses

Lucidarme J et al. J Infect, 2015

Meningococcal Disease

Clinical syndromes

• Bacteriemia (37.5%) -Meningococcemia

• Meningitis (50%)• Pneumonia (9%)• Conjunctivitis arthritis,

pericarditis, urethritis

D. Pace, A.J. Pollard / Vaccine 30S (2012) B3–9

IMD Can Result in Permanent, Long-term SequelaeOn average, 10%–20% of surviving patients

have long-term sequelae1Typical sites of IMD sequelae1-5

1. World Health Organization. Meningococcal meningitis. Fact sheet No. 141. Updated November 2015. http://www.who.int/mediacentre/factsheets/fs141/en/. Accessed August 26, 2017. 2. BettingerJA, et al. Pediatr Infect Dis J. 2013;32:e20-e25. 3. Viner R, et al. Lancet Neurol. 2012;11:774-783. 4. Borg J, et al. Pediatrics. 2009;123:e502-e509. 5. Brandtzaeg P. In: Frosch M, et al, eds. Handbook of Meningococcal Disease: Infection Biology, Vaccination, Clinical Management. Weinheim, Germany: Wiley-VCH Verlag GmbH & Co. KGaA; 2006:427-479.

Typical Symptoms of IMD Appear Later in Older Children and Adolescents, Delaying Medical Care and Increasing the Risk of Long-

term Effects of IMD

Thompson MJ, et al. Lancet. 2006;367:397-403.

Timely GP/hospital admission is critical for successful treatment of IMD.

810

15

19

13 14

2022

0

5

10

15

20

25

Meningococal disease: risk factors1–3

• Infants / adolescents• Terminal complement /

properdin deficiency• Anatomic or functional

asplenia• Lab workers• HIV+ / MSM• Genetic polymorphism

• Clonal complex• Bacterial load• Circulating endotoxins

• Household crowding• Exposure to tobacco smoke• Low socio-economic status• Urban residence

Host Pathogen

Environment

Most cases (>90%) of meningococcal disease occur in previously healthy persons without identified risk factors2

MSM were several times more likely to contract invasive meningococcal disease than other males aged 18–64 years

Kratz MM, et al. Emerg Infect Dis 2015;21:1379–86

Children and adults with HIV have increased (up to 26.5-fold) risk of meningococcal disease

Simmons R, et al. BMC Med 2015;13:297

There is a 1,000-fold increased risk of meningococcal disease (caused by unusual meningococcal strains) in patients with complement deficiency

Rosain J, et al. J Infect Dis 2017:215:1131–8

Eculizumab use has been primarily associated with an increased risk (up to 10,000-fold higher) of meningococcal infections

Benamu E, et al. Curr Opin Infect Dis 2016;29:319–29

1. Rosenstein N et al. N Eng J Med 2001;344:1378–88. 2. Kaplan SL et al. Pediatrics 2006;118:e979–84 3. MMWR. Prevention and Control of Meningococcal Disease. Available at: https://www.cdc.gov/mmwr/preview/mmwrhtml/rr4907a1.htm (accessed May 2018)

Carriage and transmission • Pharyngeal carriage is a prerequisite for invasive meningococcal

disease.• Asymptomatic carriage (may last a long time) -nasopharynx (< 1% - 30%)• N. meningitidis is predominately carried by teenagers/young adults.

Prevalence (%)

Age

0

20

40

60

0 20 40 60 80 100

Fitted dataRange of 95% CI

Christensen H et al. Lancet Infect Dis. 2010;10:853.

Worldwide Available Polysaccharide Conjugate Meningococcal Vaccines

Polysaccharide Conjugate Vaccines Carrier Protein46-53

Menjugate MenC CRM197Meningitec MenC CRM197NeisVac-C MenC TTMenitorix MenC-Hib TTMenAfriVac MenA TTMenactra MenACYW DTMenveo MenACYW CRM197Nimenrix™ MenACYW TT

New multivalent ACWY-TT and ACWYX vaccines are being developed

Menjugate® [PI]. Novartis Vaccines; 2013; 47Meningitec® [PI]. Pfizer; 2011; 48NeisVac-C® [PI]. GlaxoSmithKline Inc; 2010; 49Menitorix® [PI]. GlaxoSmithKline Australia; 2013; 50MenAfriVac® [PI]. Serum Institute of India Ltd; 51Menactra [PI]. Sanofi pasteur; 2013; 52Menveo [PI]. Novartis Vaccines; 2013; 53Nimenrix® [PI]. GlaxoSmithKline UK; 2013; 54Meningo A+C [Public assessment report]. Sanofi Pasteur; 2013; 55Mencevax® [PI]. GlaxoSmithKline Australia; 2010; 56Menomune® [PI]. Sanofi pasteur; 2012.

Meningococcal Conjugate Vaccines Represent a Significant Advance Compared With Existing Plain Polysaccharide Vaccines

Polysaccharide vaccine• Antibody response of short

duration• No memory B-cell production

Polysaccharide

B cell

Antibody production

Plasma cell

Conjugate vaccine• Antibody response of long

duration• T cells stimulate B cells to

produce antibodies• Memory B cells produced

Carrier protein

B cell

BCR

T-cell help

Polysaccharide-specific plasma cell

Antibody production

Polysaccharide-specific memory B cell

43Pollard AJ, et al. Nat Rev Immunol. 2009;9(3):213.

10

Outbreaks caused by MenC.High carriage rates of MenC in both refineries. No impact of vaccination on carriage rates

%

Ministry of Health replace the polysaccharide vaccine with the MenC conjugate vaccine for controlling MenC outbreaks

Update on safety and immunogenicity (reduced schedule,

concomitant administration and persistence data) of meningococcal

conjugate vaccines

0102030405060708090

100

SBA

titer

s≥

1:8

(%)

< 6 m

12%

5-11 m

16%

12-23 m

26%

24-35 m

23%

36-47 m

33%

Antibody Persistence 6 years After Vaccination with MenC Conjugate

48-59 m 60-83 m

26%

48%

Perrett K et al. CID, 2010

• Persistence of immunity is dependent on age at priming• These data emphasizes the importance of the herd immunity effect and

provide the first evidence supporting the introduction of a booster dose for cohorts of children immunized before school age.

Age (in months) at priming vaccination

Antibody persistence 5 years after primary vaccination with MenACWY-CRM in infants, and booster response across all serogroups2,3

1. Klein NP et al. Pediatr Infect Dis J 2012;31:64–71; 2. Baxter R et al. Hum Vaccin Immunother 2016;12:1300–1310;3. Klein NP et al. Open Forum Infect Dis 2014;1(Suppl 1):S319. Adapted from references 1–3

1 month post-dose 4(dose 4 at 12 months of age)1n=84–8628 months post-dose 4 (at 40 months of age)2

48 months post-dose 4 (at 60 months of age)2,3

Booster dose at 48 months post-dose 4(at 60 months of age)3n=103–115

*Blood drawn at 13 months of age (1 month post–dose 4), 40 months of age (28 months post–dose 4), 60 months of age (48 months post–dose 4) and 61 months of age (1 month post–booster at 60 months of age).

14

n=120–122

Time points assessed*:

**P

Real-World Impact data on Meningococcal Vaccines Programmes implemented in

Europe, Africa, North and Latin America

18

Direct and indiret protection with conjugated vaccines

Preventing the acquisition of carriage is crucial to optimize the impact of programs with conjugated vaccines

Vetter, Baxter, Sáfadi et al. ERV, 2016

19

MenC immunization programmes have reduced the burden of meningococcal C disease in Europe1–3

1. Trotter CL et al. FEMS Microbiol Rev. 2007;31:101–7; 2. Safadi M, McIntosh E. Expert Rev Vaccines 2011;10:1717–30; 3. de Greeff S et al . Pediatr Infect Dis J. 2006;25:79–80

Single dose of MenC-TT vaccine at 14 months + catch-up from 1‒18 years in Netherlands, 2002

Routine immunization programmes, including catch-up campaigns in children and adolescents, have been successful in reducing MenC disease incidence through

direct and indirect protection

54.5

43.5

32.5

21.5

10.5

0 Belgium(2002)

Iceland(2002)

Ireland(2000)

Netherlands(2000)

Spain(2000)

UK(1999)

Country (year of vaccine introduction)

Inci

denc

e

Meningococcal disease epidemiology in France, 2006-2015

Low MenC vaccination coverage in older age groups (32% in 10-14 y, 23% in 15-19 y and 7% in 20-24 y).

Incidence rates of MD, by serogroup. France, 2006-2015 Decreasing incidence of IMD cases in France from 2006 to 2015 (mainly related to the decrease in MenB cases).

Chatelet et al. Journal of Infection (2017) 74, 564e574

MenC Incidence rates. France, 2006-2015

21

• Incidence of suspected meningitis cases declined by 57% (95% CI 55–59) in vaccinated compared with unvaccinated populations.

• In fully vaccinated populations, the incidence of confirmed group A disease was reduced by more than 99%.

• The IRR for non-A serogroups was higher after completion of MenAfriVac campaigns (IRR 2·76, 95% CI 1·21–6·30).

Impact of MenA-TT vaccination in the “African belt”.

Trotter C et al. Lancet Infect Dis, May 2017

• Between 2011- 2015 > 217 million (1 – 23 y) vaccinated in 19 countries from the “meningitis belt” with MenA-TT

Emergence of MenC and MenW disease in Africa.

• By June 2015, 8,500 suspected cases of MD in Niger, including 573 deaths. Most of the cases were MenC, belonging from a newly lineage ST-10217.

• Nigeria: Dec/2016 - May/2017: 14,473 cases. 80% of tested cases were serogroup C.

• The world’s largest reported serogroup C epidemic

http://www.who.int/csr/don/23-july-2015-niger/en/ http://www.meningvax.org/files/BulletinMeningite. http://www.who.int/wer March, 2017 http://www.ncdc.gov.ng/themes/common/files/sitreps/bf8ebe6d8a8187aa9ddf1b39aecda3ae.pdfMustapha M & Harrison L. HVI, 2018

• Outbreaks of MenW cc-11 in Burkina Faso from 2012 and Togo and Ghana in 2016

• Reactive vaccinations in 2016 with polysaccharide ACW, AC and ACW and MenC conjugate vaccines

Distribution of MD cases in the meningitis belt, 2006 - 2017

http://www.who.int/csr/don/23-july-2015-niger/en/http://www.meningvax.org/files/BulletinMeningitehttp://www.who.int/werhttp://www.ncdc.gov.ng/themes/common/files/sitreps/bf8ebe6d8a8187aa9ddf1b39aecda3ae.pdf

Examples of Meningococcal conjugate vaccination

programmes without catch-up campaigns:

Brazil and Chile

Brazil started vaccination with MenC Vaccine for all children < 2 years of age on late 2010.

• Infant immunization (3 and 5 months) with booster dose at 12 months.

• Children between 12 and 23 months: 1 dose• No catch up campaign in older age groups

80%

13%5%1%

Incidence rates before and after Men C vaccination. Brazil, 2008-2015

0

2

4

6

8

10

12

14

16

< 1 a. 1-2 a 2-3 a 3-4 a 4-5 a 5-9 a 10-14 a 15-19 a 20-30 a 30-40 a 40-50 a 50-60 a > 60 a.

2008-2010 (pre-vaccine)20112012201320142015

Cases/100,000

Safadi M, et al. JPIDS. 2014;3:91-93SINAN, MS 2015.

Early impact on incidence rates of meningococcal disease observed only in the age groups targeted for vaccination.

Serogroup Distribution of MD, by age group. Brazil, 2017

SIREVA. IAL, 2017

28Macedo L et al. HUMAN VACCINES & IMMUNOTHERAPEUTICS 2018,

VaccinationVaccination

Impact of MenC conjugate vaccination programs with and without catch-up campaigns in adolescents: Bahia, Brazil

Children < 5 years of age + catch-up campaign for individuals 10–24 years of age

Only Children < 5 years of age

In Salvador, compared to the pre-vaccine period, a virtual disappearance of MenC disease was observed. However, in the state of Bahia (excluding the city of Salvador), no herd protection could be observed, with significant impact only among vaccine-eligible children within 5 years of introduction of the MCC vaccination program

Booster doses in adolescents 9-13 years with MenC conjugate vaccine.

Decision for 2017 with MenC conjugate vaccine in Brazil:

Incidence rates and CFR of Meningococcal Disease in Chile. 1990-2015

Increased incidence of MD in 2012 (from 0.4 to 0.8), associated with emergence of serogroup W (3 cases in 2010, 20 in 2011 and 60 in 2012).

http://epi.minsal.cl/epi/html/bolets/reportes/Meningitis/meningitis.pdf

CFR

(%)

Inci

denc

e ra

tes

(per

100

,000

hab

)

Reactive MenW Immunization action in Chile

http://epi.minsal.cl/epi/html/bolets/reportes/Meningitis/meningitis.pdf

• An immunization campaign started in 2012 with the tetravalent conjugate vaccine (Men ACWY), initially targeting children aged 9 months to < 5 years.

• 9 m to < 2 y: 2 doses (MenACWY-DT) and > 2 y: 1 dose (MenACWY-CRM).

• Approximately 1 million children vaccinated (Coverage >95%).

• From 2014: 1 dose (MenACWY-TT) in toddlers at 12 months.

Impact of the MenACWY immunisation campaign in Chile, 2012-2017

Inci

denc

e ra

tes

(cas

es/1

000)

ISP, Chile

82% reduction

• Reduction of 82% in the incidence rates of MD in children aged 1- 5 years• No significant impact on incidence rates of other unvaccinated age groups

Age (years)http://epi.minsal.cl/epi/html/bolets/reportes/Meningitis/meningitis.pdf. 2017http://www.ispch.cl/sites/default/files/Informe%20Neisseria%20meningitidis%20%20SE%201-5%202018%20v%203.pdf

0

5

10

15

20

< 1Y 1-5 Y 6y - 9 y 10y - 19y 20y - 59y > 60y

201220132014201520162017

Pre-vaccine

Post-vaccine

http://epi.minsal.cl/epi/html/bolets/reportes/Meningitis/meningitis.pdf

Number of cases of serogroup W cases. Chile, 2010 - 2017

0

20

40

60

80

100

120

2010 2011 2012 2013 2014 2015 2016 2017

serogroup W cases

W

ACWY Vaccination

http://epi.minsal.cl/epi/html/bolets/reportes/Meningitis/meningitis.pdf. 2017http://www.ispch.cl/sites/default/files/Informe%20Neisseria%20meningitidis%20%20SE%201-5%202018%20v%203.pdf

http://epi.minsal.cl/epi/html/bolets/reportes/Meningitis/meningitis.pdf

Meningococcal Disease in US.

• In 2016, 372 cases of MD reported (0.12/100,000). Declining incidence rates.

• 49 deaths (CFR 13%)

CDC, 2018 (http://www.cdc.gov/meningococcal/surveillance/)

• Highest rates in infants, followed by a second peak in adolescence (16-23 y) and elderly.

• Serogroup B causes ~ 60% of cases in children < 5 years old. Serogroups C, Y, or W cause 73% of the cases among persons > 11 years old.

37

Age Group Primary BoosterIndividuals 11–21 years

11–12 years 1 dose Given if 1st dose before 16th birthday

5 years post primary; 13–18 years (not vaccinated) 1 dose

19–21 year (not vaccinated by 16) 1 dose as catch-up

High risk individuals

2–18 months at high risk 4 doses at2, 4, 6, 12–15 months

2 mos–6 years: 3 years post primary; Every 5 years thereafter

≥7 years: 5 years post primary; Every 5 years thereafter

9–23 months at high risk 2 doses 12 weeks apart

2–55 years at high risk 2 doses 12 weeks apart

2–55 years students, travelers, etc 1 dose

≥56 years MPSV4 (primary recommendation)

Every 5 years with MenACWY if the person remains at risk

Recommendation of meningococcal vaccination in USA (ACIP)

MMWR, 2016

Men ACWY conjugate vaccine is routinely recommended for all adolescents and high risk individuals.

Vaccine effectiveness of MenACWY-D: Case-Control Study in Adolescents*

Cases (N=183)*Controls (N=199) VE (95% CI)

Vaccinated < 1 year 79% (54%-93%)

Vaccinated 1< 3 years 69% (44%-83%)

Vaccinated ≥ 3-8 years 61% (25%-79%)

McNeil J et al. PEDIATRICS Volume 139 , number 2 , February 2017

• Vaccine effectiveness was 77% and 51% for serogroups C and Y, respectively. Vaccine effectiveness against serogroup W could not be calculated due to the low incidence.

• Effectiveness waned 3 to

39

The “South-American” serogroup W evolution.

An expanding South American/UK MenW strain was distinct from the ‘Hajj outbreak’ strain.Jay Lucidarme et al. Journal of Infection 2015

These data also demonstrate the co-circulation of W ST-11 strains in South America, UK and other regions that are phylogenetically and antigenically distinct from the Hajj cloneMustapha M et al. Ebio Medicine, 2015

The Jamboree-associated cluster formed part of a novelstrain, the proposed ‘2013-strain’, which emerged in the UK in 2013.Lucidarme J et al. Euro Surveill. 2016

40

Emergence of serogroup W in UK• In the light of the rapidly increasing W (cc11) disease from 2009/10

to 2014/15, ACWY conjugate vaccine was introduced in late 2015 for 13-18 years teenagers and university freshers and is intended to induce herd protection.

Campbell H et al, Euro Surveill. 2015; Campbell H et al, Euro Surveill. 2016

• A quarter of cases occurred in children aged

41

No cases in adolescents vaccinated with MenACWY.Early estimated vaccine effectiveness was 100% (−47% - 100%)

Observed and projected cases of W, Y, and B MD in England among persons who left school

• MenACWY coverage of 36,6% among persons who left school.

• During the first 12 months of the MenACWY vaccination program for teenagers, a 69% decrease (18%–88%) was observed.

Campbell H et al. Emerg Infect Dis. 2017 Jul

Meningococcal Disease, Australia 2002-2017.

• There is currently an outbreak of Meningococcal W (MenW) in Central Australia.

• In response, six states have started a meningococcal ACWY vaccination program for individuals in affected communities. The programs target adolescents aged 15-19 years, with NSW targeting 17-18 year olds..

http://www.health.gov.au/internet/main/publishing.nsf/Content/ohp-meningococcal-W.htm

43

Serogroup W disease in Netherlands

Knol M et al. Lancet Public Health 2017; 2: e473–82

• In the Netherlands, the incidence of meningococcal serogroup W disease increased substantially in 2015–16 compared with 2014–15, with an incidence rate ratio of 5·2 (95% CI 2·0−13·5) and 11% case fatality

Cases of MenW disease caused by the South American MenW:cc11 strain sublineage

• The outbreak started mainly among people aged 65 years and older, with an increase among 10−19 year olds in 2016

• MenC was replaced by MenACWY in adolescents to prevent further serogroup W cases and deaths

1. Tsang RSW, et al. Can Commun Dis Rep 2017; 43:144–9. 2. Tsang RSW, et al. Int J Infect Dis 2018;69:55–62

Emergence of MenW in Canada

• Increase of MenW in Canada, associated with emergence of ST-11 CC.

• The % of Men W isolates varied from 2.7% in 2012 to18.8% in 20161

• WGS: evidence of presence “Hajj-related” and non-Hajj MenW ST-11 CC (related to “South American sub-lineage strains”)2

Canada

Prevalence of carriage by serogroup

Despite 71% MenACWY vaccine coverage, carriage of group W increased substantially.

Majority belongs to MenW:ST-11 cloneOldfield N et al. EID, 2017

0

2

4

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8

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12

sep/15 nov/15 mar/16

Carri

age

preva

lence

(%)

NG B Y W Non BWY

cross-sectional meningococcal carriage study in first-year UK university students

Meningococcus B capsule is a self antigen, poorly immunogenic and cannot be used for vaccination

1Häyrinen J, et al. J Infect Dis. 1995;171:1481-1490; 2Finne J, et al. J Immunol. 1987;138:4402-4407; 3Bruge J, et al. Vaccine. 2004;22:1087-1096;

• Structurally identical polysialic acid units in fetal neural tissue

• Poorly immunogenic1,2• No functional activity of

vaccine-induced AB3

The polysaccharide capsule?

Poorly immunogenic1

A single subcapsular protein component?

Susceptible to antigenic variability2,3

Multiple subcapsular components?

Enables broad coverage across a number of strains4

A Multicomponent Approach to MenB Vaccination

1. Häyrinen J, et al. J Infect Dis. 1995;171:1481-1490; 2. Sadarangani M, et al. Lancet Infect Dis. 2010;10:112-124; 3. Tan LK, et al. N Engl J Med. 2010;362:1511-1520; 4. Donnelly J, et al. Proc Natl Acad Sci U S A. 2010;107:19490-19495.

Neisseria meningitidis

Factor H (fH) binding protein (fHBP) vaccine - Pfizer• Virulence factor

• Binds fH→ down regulates alternative complement pathway

• 3 variant groups:

• Variant 1 (family B),

• Variants 2 and 3 (family A).

• Two lipidated LP2086 variants in Pfizer vaccine were selected (one from each subfamily)

• 2 doses: 0 – 6 months or 3 doses: 0, 1-2 and 6 months (10 – 25 years of age)

MATS Concept

Are any of the 4CMenB components in the circulating strains: (i) expressed to a sufficient degree, and (ii) similar enough to the antigens in the vaccine such that the antibodies

generated by 4CMenB will kill the bacteria?

MATS can determine the minimum amount of recognizable antigen needed to result in bacterial killing, for each of the four components*

1. fHbp, NHBA and NadA assessments use ELISA PHENOTYPIC2. PorA assessment uses PCR sequencing GENOTYPIC

*individually

4CMenB Vaccine - GSK

4CMenB Vaccine Licensed Immunization SchedulesEuropean Union

BEXSERO [summary of product characteristics].

3 Doses2–5 months

6–11 months

12–23 months

2–10 years

11+ years

≥1 month 1 Dose age 12–15 mo*

2 Doses

≥2 months

≥1 month

1 Dose in the 2nd year of life≥2 mo post–primary series

1 Dose 12–23 mo post–primary series

Need not established

Age Group Primary ImmunizationInterval Between Primary Doses Booster

*In case of delay, the booster should not be given later than 24 months.

Canada (2006–2009): Bettinger JA, et al. Vaccine. 2013;32:124-130; United States (2000–2008, data downweighted with Oregon outbreak strains): Kim E, et al. Presented at: 18th IPNC. September 9-14, 2012. Würzburg, Germany. Poster P270; Brazil (2010): Lemos AP, et al. Presented at: 18th IPNC. September 9-14, 2012. Würzburg, Germany. Poster P272; Norway, United Kingdom, Germany, France and Italy (July 2007–June 2008), Spain (2008–2010): Vogel U, et al. Lancet Infect Dis. 2013;13:416-425; Greece (2008–2010): Data on file, Novartis Vaccines and Diagnostics; Ireland (2009–2013): Data on file, Novartis Vaccines and Diagnostics; Australia (2007–2011): Tozer SJ, et al. Poster presented at: 27th ICP; August 24-29, 2013. Melbourne, Australia.

Estimated Potential MenB Strain Coverage for specific countries based on MATS

85%

73% 82%85%

87%85%82%

87%

85%

73%

69%88%

74%

76%

66%

91%

81%

68%

Read R et al. ESPID 2013

Impact of 4CMenB on carriage.

Outbreak of serogroup B disease in Saguenay-Lac-Saint-Jean, Canada.

• Serogroup B (ST-269) clone emerged in Quebec, Canada.

• Incidence rate of 3.4/100,000 from 2006 to 2013.

• After vaccination of population (2 m-20 years) with 4CMenB decreases were, respectively 92% and 67%, in age-group ≤20 years and in those > 20 years

De Wals et al. CID, 2017

Meningococcal disease on US college campuses, 2013–17

1. http://www.nmaus.org/wp-content/uploads/2017/12/NMA-College-Outbreak-Map-December-11-2017.pdf2. MMWR Morb Mortal Wkly Rep. 2015

UK Immunization Recommendations for Meningococcal Vaccines

AGE Immunisation (Vaccine Given)

2 months • MenB

4 months • MenB

Between 12 - 13 months

• Hib/MenC (combined as one injection); plus: • MenB

13-18 years • Men ACWY - given to 17-18 year olds and first time students up to 25 years.

http://www.nhs.uk/conditions/vaccinations/pages/vaccination-schedule-age-checklist.aspx

MenACWY – recommended for travelers to Mecca for religious festivals of Hajj or Umrah

Impact: Comparing with the pre-vaccine period, a 50% reduction in MenB incidence rates was observed in the cohorts eligible for vaccination (p=0·0001).

Lancet, online 27 October 2016

Effectiveness:• One dose of the vaccine: 22% (95% CI –105 to 67,1).• Two doses of the vaccine: 82,9% (95% CI 24,1–95,2).• At least one dose of the vaccine: 64% (95% CI 8,9–84).

UK introduced the MenB vaccination in September 2015 for infants at two and four months of age, with a booster dose at 12-13 months (high coverage)

58

Age distribution of group W cases, by academic year, England, 2011 – 2016.

Cases and incidence rates increased in every age group except persons 15–19 years of age (31% reduction) and infants

• Samples of infants vaccinated with Bexsero presented hSBA > 1/32 against W cc11 meningococcal strains.

60

Lancet 2017

Booster doses in adolescents with conjugate vaccines.

Use of the protein-based Men B vaccines

Considerations for the future with meningococcal vaccines:

Slide Number 1Neisseria meningitidisMeningococcal DiseaseIMD Can Result in Permanent, Long-term SequelaeTypical Symptoms of IMD Appear Later in Older Children and Adolescents, Delaying Medical Care and Increasing the Risk of Long-term Effects of IMDMeningococal disease: risk factors1–3Carriage and transmission Worldwide Available Polysaccharide Conjugate Meningococcal Vaccines�Meningococcal Conjugate Vaccines Represent a Significant Advance Compared With Existing Plain Polysaccharide VaccinesOutbreaks caused by MenC.�High carriage rates of MenC in both refineries. �No impact of vaccination on carriage ratesUpdate on safety and immunogenicity (reduced schedule, concomitant administration and persistence data) of meningococcal conjugate vaccinesSlide Number 13Antibody persistence 5 years after primary vaccination with MenACWY-CRM in infants, and booster response across all serogroups2,3Antibody persistence after MenACWY-CRM or MenACWY-DT up to 5 years after primary vaccination in adolescents aged 11–18 yearsSlide Number 17Direct and indiret protection with conjugated vaccinesMenC immunization programmes have reduced the burden of meningococcal C disease in Europe1–3Meningococcal disease epidemiology in France, 2006-2015Slide Number 21Emergence of MenC and MenW disease in Africa.Examples of Meningococcal conjugate vaccination programmes without catch-up campaigns:�Brazil and ChileSlide Number 24Incidence rates before and after Men C vaccination. Brazil, 2008-2015Serogroup Distribution of MD, by age group. Brazil, 2017Slide Number 28Slide Number 29Slide Number 30Slide Number 31Impact of the MenACWY immunisation campaign in Chile, 2012-2017Number of cases of serogroup W cases. Chile, 2010 - 2017Meningococcal Disease in US. Recommendation of meningococcal vaccination in USA (ACIP)Vaccine effectiveness of MenACWY-D: Case-Control Study in Adolescents*The “South-American” serogroup W evolution. Emergence of serogroup W in UKNo cases in adolescents vaccinated with MenACWY.�Early estimated vaccine effectiveness was 100% (−47% - 100%)Meningococcal Disease, Australia 2002-2017.Slide Number 43Emergence of MenW in CanadaPrevalence of carriage by serogroupMeningococcus B capsule is a self antigen, poorly immunogenic and cannot be used for vaccinationA Multicomponent Approach to �MenB VaccinationFactor H (fH) binding protein (fHBP) vaccine - PfizerMATS Concept4CMenB Vaccine Licensed Immunization Schedules�European UnionEstimated Potential MenB Strain Coverage for specific countries based on MATS Slide Number 52Slide Number 53Outbreak of serogroup B disease in Saguenay-Lac-Saint-Jean, Canada. Meningococcal disease on US college campuses, 2013–17UK Immunization Recommendations for Meningococcal Vaccines�Slide Number 57Age distribution of group W cases, by academic year, England, 2011 – 2016.Slide Number 59Slide Number 60Slide Number 61