JCVI recommendation on MenB vaccine

Serogroup B Meningococcus

• Commonest cause of meningococcal disease in UK

• Similar to antigen on foetal brain tissue

• Other vaccine targets being investigated (OMPs)

• A group B vaccine was always 5 years away!

Meningococcal Cell Wall

MeNZB vaccine

• Epidemic of group B P1.7-2,4

• Tailor made vesicle vaccine for <20s

• Effectiveness ~73%• (against epidemic strain)

Clin Infect Dis 2009;49:597–605

Meningococcal disease in New Zealand 1970–2007

Reverse vaccinology

• Genome of serogroup B strain used to identify vaccine candidates

• 350 candidate antigens expressed

• Identified 7 proteins; surface exposed, conserved, induce bactericidal antibody response

Science 2000;287:1816-20

4CMenB vaccine

• Neisseria Heparin-Binding antigen (NHBA)• Neisserial adhesin (NadA) • Factor H-binding protein (fHbp)• PorA from MeNZB

Men B vaccine;What do the JCVI want to know?

• Is it effective?• Is it safe?• Is it worth it?

Invasive meningococcal B infections, E&W; 1998-2012

<1 1-4 5-9 10-14 15-19 20-24 25-29 30-34 >350

1000

2000

3000

4000

5000

6000

Age (Years)

Immunogenicity in Infants

• 4CMenB vaccination at 2, 3, and 4 months with routine vaccines + 12 month booster

• 88 - 99% infants developed hSBA titers ≥1:5 against indicator strains

• Responses to routine vaccines non-inferior (except pertactin and Pneumo 6B)

JAMA 2012;307:573-82, Lancet 2013;381:825-835

Immunogenicity in InfantsLancet 2013;381:825-835

What will 4CMenB cover?

Lancet Infect Dis. 2013 ;13:416-25

Meningococcal antigen typing system (MATS)78% of European MenB strains would be killed

88% strains (E&W2007-2008) killed in hSBA assay.

Vaccine 2013; 31: 4968-74.

Safety in Infants

• “Most notable systemic reaction was fever” esp when co-administered with routine imms

• More anti-pyretic use – prophylactic paracetamol advised

• 4 cases of Kawasaki disease

Lancet 2013;381:825-835

DUTY ON THE SECRETARY OF STATE FOR ENGLAND

• The Health Protection (Vaccination) Regulations 2009 place a duty on the Secretary of State for Health in England to ensure, so far as is reasonably practicable, that the recommendations of JCVI are implemented,

where those recommendations:

DUTY ON THE SECRETARY OF STATE FOR ENGLAND

a. New national vaccination programme;b. made by JCVI;c. in response to a question by the Secretary of

State; d. based on an assessment which demonstrates

costeffectiveness;e. not travel or occupational health vaccines.

Cost-effectiveness

Meningococcal vaccines likely to be cost effective;

• when the incidence of disease is high• if vaccine gives “indirect protection” (herd

immunity from preventing carriage)

Invasive meningococcal infections, England and Wales

0

500

1,000

1,500

2,000

2,500

3,000

YW135CB

1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013

Incidence of disease is low

Meningococcal carriage by age

Lancet Infect Dis. 2010;10:853-61.

Infants 4•5% 19-year olds 23•7% 50-year olds 7•8%

Economic and mathematical modelling study of potential impact

• Unlikely to be cost-effective in the NetherlandsHum Vaccin Immunother. 2013;9(5).

• In UK could prevent 27% of cases by vaccinating infants

• Could prevent 71% case by vaccinating infants PLUS catch-up campaign, if vaccine protects against carriage

Vaccine. 2013 Apr 5. pii: S0264-410X(13)00369-1

• Data on 4CMenB preventing carriage in teenagers - uncertain

Interim position statement Men BJuly 2013

• “on the basis of the available evidence routine infant or toddler immunisation is highly unlikely to be cost effective at any vaccine price”

• JCVI found assessment challenging – absence of key data

• JCVI concerned about adverse impact – large uncertainties

Needs;- population based evaluation in adolescents; ?carriage effect- evaluation of infant immunisation in a large cohort (i.e. The UK)

MenB statement March 2014

• A programme providing vaccinations at 2, 4, and 12 months schedule was likely to be both effective and cost-effective, albeit at a price significantly lower price than the list price for Bexsero®.

• Even in the most favourable of scenarios no infant programme could demonstrate cost-effectiveness at the list price for Bexsero®.

Recommendation – March 2014

• JCVI recommended a programme for use of the MenB vaccine at 2, 4, 12 months of age in a carefully planned programme.

• Plans for implementation should anticipate a sustainable and cost-effective programme.

• Advised a targeted carriage study in adolescents to assess the impact on carriage.

Men B vaccine;What do the JCVI want to know?

• Is it effective? – immunogenic?coverage, ?efficacy

• Is it safe? – fevers, ?Kawasaki>5000 infants and toddlers

• Is it worth it? – cost effective at low vaccine price