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Bexsero

Common name:

4CMenB, meningococcal B vaccine

Protects against meningococcal disease caused by Neisseria meningitidis group B.

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Overview

Meningococcal disease is caused by the bacterium Neisseria meningitidis. At least 12 groups have been identified, including groups A, B, C, Y and W (previously called W-135). The pattern of disease caused by each group varies by time and country or geographical areas. In New Zealand over 2009–2016, meningococcal group B caused 53–72% of disease, and meningococcal groups C, Y and W, including the very virulent group W ST-11 type, caused 25–46% of disease. Meningococcal group A rarely causes disease in New Zealand.

Bexsero®, a multicomponent recombinant vaccine against meningococcal group B disease only is now available in New Zealand. Bexsero was first approved for use in Europe in 2013, since then the vaccine has been approved for use in more than 40 countries including Australia, the United Kingdom and the United States. Conjugated meningococcal vaccines that protect against either groups A, C, W and Y or group C disease only are also available in New Zealand. For best protection against all meningococcal disease in New Zealand, separate vaccinations against group B disease and groups A, C, Y and W disease are recommended.

Bexsero is broadly protective against meningococcal group B disease and is different to the MeNZB™ vaccine used in New Zealand between 2004 and 2011. The MeNZB vaccine was designed to target a specific type of meningococcal group B bacterium that only caused disease here in New Zealand. MeNZB was not meant for long term use. The vaccine was withdrawn once the rate of disease was significantly reduced. However, the active component of the MeNZB vaccine has contributed to the successful development of Bexsero.

In New Zealand, Bexsero is only available as a purchased vaccine through your family doctor.

For individuals with a medical condition that increases their risk of invasive meningococcal disease AND is listed on the Pharmaceutical Schedule, the meningococcal vaccines NeisVac-C® and/or Menactra® are available as funded vaccines. However, these vaccines do not provide protection against meningococcal group B disease.

Responses to vaccine

Bexsero (4CMenB)

Common responses

  • Fever over 38°C in children aged under 2 years
  • Redness, swelling and/or mild–moderate pain around injection site
  • Irritability, unusual crying
  • Decreased appetite, nausea
  • Headache, muscle and/or joint aches.
  • Malaise, drowsiness

Rare responses

  • Urticaria (allergic skin reaction)
  • Anaphylaxis (severe allergic reaction)

As with any medicine, very rarely a severe allergic reaction (anaphylaxis) can occur following immunisation.

References

  • Das RR, Panigrahi I, Naik SS. The effect of prophylactic antipyretic administration on post-vaccination adverse reactions and antibody response in children: A systematic review. PLoS One. 2014;9(9):e106629.
  • Flacco ME, Manzoli L, Rosso A, Marzuillo C, Bergamini M, Stefanati A, et al. Immunogenicity and safety of the multicomponent meningococcal B vaccine (4CMenB) in children and adolescents: A systematic review and meta-analysis. Lancet Infect Dis. 2018;18(4):461-72.
  • Gossger N, Snape MD, Yu LM, Finn A, Bona G, Esposito S, et al. Immunogenicity and tolerability of recombinant serogroup B meningococcal vaccine administered with or without routine infant vaccinations according to different immunization schedules: A randomized controlled trial. JAMA. 2012;307(6):573-82.
  • Hong E, Terrade A, Taha M-K. Immunogenicity and safety among laboratory workers vaccinated with Bexsero vaccine. Hum Vaccin Immunother. 2017;13(3):645-8.
  • Institute of Environmental Science and Research Ltd. Notifiable diseases in New Zealand: Annual report 2016. Porirua: Institute of Environmental Science and Research Ltd (ESR), (2017) FW17028. 
  • Iro MA, Snape MD, Voysey M, Jawad S, Finn A, Heath PT, et al. Persistence of bactericidal antibodies following booster vaccination with 4CMenB at 12, 18 or 24 months and immunogenicity of a fifth dose administered at 4 years of age - A phase 3 extension to a randomised controlled trial. Vaccine. 2017;35(2):395-402.
  • Jackson C, Yarwood J, Saliba V, Bedford H. UK parents’ attitudes towards meningococcal group B (MenB) vaccination: A qualitative analysis. BMJ open. 2017;7(4):e012851.
  • Kimura A, Toneatto D, Kleinschmidt A, Wang H, Dull P. Immunogenicity and safety of a multicomponent meningococcal serogroup B vaccine and a quadrivalent meningococcal CRM197 conjugate vaccine against serogroups A, C, W-135, and Y in adults who are at increased risk for occupational exposure to meningococcal isolates. Clin Vaccine Immunol. 2011;18(3):483-6.
  • Lopez L, Sherwood J. The epidemiology of meningococcal disease in New Zealand 2013. Wellington: Institute of Environmental Science and Research Ltd (ESR), (2014) FW14023. 
  • Martinon-Torres F, Safadi MAP, Martinez AC, Marquez PI, Torres JCT, Weckx LY, et al. Reduced schedules of 4CMenB vaccine in infants and catch-up series in children: Immunogenicity and safety results from a randomised open-label phase 3b trial. Vaccine. 2017;35(28):3548-57.
  • Martinon-Torres F, Carmona Martinez A, Simko R, Marquez PI, Arimany J-L, Gimenez-Sanchez F, et al. Antibody persistence and booster responses 24-36 months after different 4CMenB vaccination schedules in infants and children: A randomised trial. J Infect. 2018;76(3):258-69.
  • Medsafe. New Zealand data sheet: Bexsero [Internet]. Wellington: New Zealand Medicines and Medical Devices Safety Authority; 2018 [cited 2018 August 14]. Available from: http://www.medsafe.govt.nz/profs/Datasheet/b/bexseroinj.pdf.
  • Parikh SR, Andrews NJ, Beebeejaun K, Campbell H, Ribeiro S, Ward C, et al. Effectiveness and impact of a reduced infant schedule of 4CMenB vaccine against group B meningococcal disease in England: A national observational cohort study. Lancet. 2016;388(10061):2775-82.
  • Prymula R, Siegrist CA, Chlibek R, Zemlickova H, Vackova M, Smetana J, et al. Effect of prophylactic paracetamol administration at time of vaccination on febrile reactions and antibody responses in children: Two open-label, randomised controlled trials. Lancet. 2009;374:1339-50.
  • Prymula R, Habib A, François N, Borys D, Schuerman L. Immunological memory and nasopharyngeal carriage in 4-year-old children previously primed and boosted with 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) with or without concomitant prophylactic paracetamol. Vaccine. 2013;31(16):2080-8.
  • Prymula R, Esposito S, Zuccotti GV, Xie F, Toneatto D, Kohl I, et al. A phase 2 randomized controlled trial of a multicomponent meningococcal serogroup B vaccine (I): Effects of prophylactic paracetamol on immunogenicity and reactogenicity of routine infant vaccines and 4CMenB. Hum Vaccin Immunother. 2014;10(7):1993-2004.
  • Vesikari T, Esposito S, Prymula R, Ypma E, Kohl I, Toneatto D, et al. Immunogenicity and safety of an investigational multicomponent, recombinant, meningococcal serogroup B vaccine (4CMenB) administered concomitantly with routine infant and child vaccinations: Results of two randomised trials. Lancet. 2013;381(9869):825-35.
  • Watson PS, Turner DPJ. Clinical experience with the meningococcal B vaccine, Bexsero: Prospects for reducing the burden of meningococcal serogroup B disease. Vaccine. 2016;34(7):875-80.
  • Wysocki J, Center KJ, Brzostek J, Majda-Stanislawska E, Szymanski H, Szenborn L, et al. A randomized study of fever prophylaxis and the immunogenicity of routine pediatric vaccinations. Vaccine. 2017;35(15):1926-35.
In Depth

Other brands:

Meningococcal group B only vaccine

  • None

Meningococcal A, C, Y and W conjugate vaccine:

  • Menactra®
  • Nimenrix®

Meningococcal C only conjugate vaccine:

  • NeisVac-C®

Vaccine type: Multicomponent, recombinant

Schedule and administration

Bexsero® is not funded in New Zealand but is available for purchase.

Bexsero is recommended but not funded for individuals at increased risk of infection with or exposure to group B meningococcal bacteria including:

  • Individuals pre/post-splenectomy or with functional asplenia
  • HIV positive individuals
  • Individuals with inherited or acquired complement deficiency
  • Pre/post-solid organ transplantation
  • Following stem cell/bone marrow transplantation
  • Prior to immunosuppression for longer than 28 days
  • Other infants and young children aged under 5 years, adolescents and young adults.
    • Particularly adolescents and young adults living in close proximity to each other, e.g. boarding school, university halls of residence or in long-term institutional care
  • Travellers to high-risk countries and Hajj pilgrims
  • Laboratory workers regularly exposed to meningococcal cultures

Special groups

Bexsero is not funded for any special groups.

Catch-up doses

Bexsero and MeNZB vaccines are not interchangeable in a course of vaccines to protect against meningococcal group B disease. 

The recommended dose schedule for Bexsero does not change for individuals with a history of immunisation with MeNZB vaccines. Bexsero utilises four antigen components to induce broad protection against meningococcal group B disease and is significantly different to MeNZB that utilised only one of these antigen components.

Storage and preparation

  • Bexsero is provided as a 0.5mL suspension in a pre-filled syringe in a single-dose pack.
  • During storage, a fine off-white deposit may form in the syringe. Shake the vaccine well before use to ensure the ingredients are evenly distributed within the vaccine.
  • Store the vaccine as per the cold chain between 2°C to 8°C. Protect from light. 

Administration

Bexsero is administered by deep intramuscular injection into the vastus lateralis in infants or deltoid in older children, adolescents and adults.

Bexsero can be administered at the same visit as other vaccines in separate syringes and at separate injection sites. When giving two intramuscular (IM) injections in the same limb in infants, the vastus lateralis is preferred because of its greater muscle mass. The injection sites should be on the long axis of the thigh and separated by at least 2 cm so that localised reactions will not overlap.

Bexsero is approved for use from 8 weeks of age. The recommended number of Bexsero doses is determined by the age of the individual when they receive their first Bexsero vaccination. The recommended number of Bexsero doses is determined by the age of the individual when they receive their first Bexsero vaccination. The recommended Bexsero vaccination schedules are shown in table 1.

 Table 1: Bexsero vaccination schedules

 Age when Bexsero first dose given  Number and timing of doses
 Infants ≥8 weeks
 to ≤5 months
 – 3 doses* with a minimum interval of 4 weeks between each dose plus
 – Booster dose a minimum of 6 months later and aged ≥12 months
 Infants ≥6 months
 to ≤11 months
 – 2 doses separated by 8 weeks plus
 – Booster dose a minimum of 2 months later and aged ≥12 months
 Children ≥12 months
 to ≤10 years
 – 2 doses separated by 8 weeks
 – The need for a booster dose has not yet been established
 Adolescents and adults ≥11 years
 to ≤50 years
 – 2 doses separated by 4 weeks
 – The need for a booster dose has not yet been established

*This recommendation may change to a two-dose course in future, after thorough consideration of recently published data.

Vaccine safety

Bexsero was first licensed in Europe in 2013 and is now licensed in over 40 countries including England and Australia. Bexsero has an excellent safety record. The most common vaccine responses include fever and discomfort or pain around the injection site. Infants and children may also be irritable, have unusual crying or a decreased appetite, whilst adolescents and adults may experience headache, muscle or joint aches, malaise or nausea. Very rarely, a severe allergic reaction (anaphylaxis) to a component in the vaccine occurs.

Fever and local vaccine responses

Fever is part of a robust immune system response to Bexsero, usually peaking around 6 hours after vaccination and settling over 24–48 hours. A fever over 38°C is more likely to occur in infants and children aged under 2 years after vaccination with Bexsero compared with other routinely used infant vaccines. When Bexsero is administered at the same visit as other Immunisation Schedule vaccines, a fever over 38°C or 39°C is almost twice as likely as when the Immunisation Schedule vaccines are given alone.

Similarly, redness, swelling and/or mild–moderate pain around the injection site are also common expected immune responses to Bexsero, peaking on the day of vaccination followed by a significant decrease, and settling from around 24 hours after vaccination.

Recommendation for use of prophylactic paracetamol

The advice for the use of prophylactic paracetamol for children aged under 2 years (refer to box 1) only applies to immunisation events when Bexsero is administered, either as the only vaccine or with other vaccines. This is because of the evidence of a robust immune response to Bexsero in young children and that the use of prophylactic paracetamol around fever over 39°C, and injection site pain. Some infants will still develop a fever and/or injection site pain even though they have received paracetamol doses. 

A review of multiple studies identified that ibuprofen is less effective than paracetamol in preventing a fever of 38°C or higher or injection site pain. Ibuprofen is not recommended to manage the symptoms of a robust vaccination response. 

Non-pharmaceutical management of fever or injection site pain

Other strategies that can also be used to help manage fever and injection site discomfort or pain are described in box 2.

 Box 1: Use of prophylactic paracetamol in children aged under 2 years to help manage post-Bexsero fever

Note: This advice only applies to immunisation events when Bexsero is administered, either as the only vaccine or with other vaccines.

Prophylactic paracetamol use is recommended with every dose of Bexsero in children aged under 2 years:

  • Three doses of paracetamol (15mg/kg) are recommended with 6 hours between each dose, whether the child has a fever or not:
    • The first dose administered 30 minutes prior to Bexsero
      • If the first paracetamol dose has not been given before the child is vaccinated, administer the dose at the time of vaccination
    • The second paracetamol dose is given 6 hours after the first dose, the third dose is given a further 6 hours later.
  • If the infant or child is sleeping when the second or third paracetamol dose is due:
    • It is not necessary to wake the child
    • The dose can be given when the child wakes up as long as it is at least 6 hours since the previous dose was given
  • Ensure parents:
    • Have the 120mg/5mL paracetamol strength formulation
      • The doctor can provide a prescription for them to fill at the pharmacy
    • Measure the paracetamol dose using a measuring spoon or syringe
  • If the child is miserable or distressed because of a fever or injection site pain 6 hours after the third dose of paracetamol and is otherwise well:
    • The parent can continue to administer the paracetamol doses with a minimum of 6 hours between doses until the discomfort resolves or 48 hours after vaccination, whichever occurs first
      • No more than four doses of paracetamol can be given in a 24-hour period
  • A child who is miserable or distressed because of a fever or injection site pain 48 hours or more after vaccination is advised to be seen by their doctor 

 

Box 2: Other strategies to help manage fever or injection site discomfort or pain

If the child has a fever

  • Give lots of breastfeeds or fluids
  • Undress them to a single layer
  • Make sure the room is not too hot or too cold
  • Give lots of cuddles

If the child has injection site discomfort or pain

  • Do not rub the injection site
  • Hold a cool damp cloth or an ice pack well wrapped in a dry cloth on the injection site
  • Give lots of cuddles

Bexsero should not be given to:

  • Anyone with severe allergy (anaphylaxis) to a previous dose of the vaccine or any component of the vaccine
  • Administration of Bexsero should be postponed in individuals suffering from a fever over 38°C.
    • The presence of a minor infection is not a reason to delay immunisation.

Specialist advice should be sought for the following groups:

  • Those with bleeding disorders, such as haemophilia. The vaccine should be administered in accordance with the haematologist’s instructions

Vaccine effectiveness

Immunisation generates circulating antibodies. Over time, the antibody levels decrease. The number and quality of antibodies and how long they last depend on what type of vaccine is used, the meningococcal group(s) covered by the vaccine, and the age of the person receiving the vaccine. 

As there are generally low numbers of meningococcal disease cases in countries such as Australia, England, Germany, New Zealand and the United States, it is not possible to determine exactly how many cases of disease  are prevented by vaccination or how long protection after vaccination lasts. Instead, the immune system response and antibody levels are used as an alternative measure of how well and how long meningococcal vaccines can protect from disease. 

Bexsero is expected to provide protection against disease caused by a broad range of group B meningococcal bacterium types, including the New Zealand specific type of meningococcal group B. On average in New Zealand, meningococcal group B causes around  two-thirds of meningococcal disease each year.

Table 2 shows the expected protection against group B meningococcal disease after completion of an age appropriate course of Bexsero. 

 Table 2:  Expected protection against meningococcal disease after vaccination with Bexsero

 Age group Expected protection
 Under 2 years  63–100%
 2–3 years  97–100%
 4–10 years  72–100%
 Adolescents  99–100%
 Adults  91–100%
 Duration of protection  
 Under 5 years  1–3 years
 Older children, adolescents and adults  Not yet established

 

Last updated: Nov 2018