Meningococcal Group B Vaccine (Monograph)

Brand names: Bexsero, Trumenba
Drug class: Vaccines
VA class: IM100

Introduction

Inactivated (recombinant) vaccine.^{1 2} Meningococcal group B (MenB) vaccine is commercially available in the US as 2 different vaccines: MenB-4C (Bexsero) and MenB-FHbp (Trumenba).^{1 2} MenB-4C contains 3 recombinant cell surface proteins (neisserial adhesion A [NadA], neisserial heparin-binding antigen [NHBA], factor H-binding protein [FHbp]) and outer membrane vesicles (OMV) containing outer membrane protein PorA (serosubtype P1.4).^{1 15} MenB-FHbp contains 2 FHbp variants, one from FHbp subfamily A (A05) and one from FHbp subfamily B (B01).²

Uses for Meningococcal Group B Vaccine

Prevention of Meningococcal Group B Infection

Prevention of Neisseria meningitidis serogroup B infection in adults, adolescents, and children 10 through 25 years of age.^{1 2 3 4 20 199 200} Also recommend in certain adults ≥26 years of age^{† [off-label]} at increased risk for meningococcal infection caused by N. meningitidis serogroup B.^{4 200}

N. meningitidis can cause invasive meningococcal disease that usually presents as acute, severe and potentially life-threatening meningitis and/or meningococcemia with abrupt onset;^{105 166 228} transmitted person to person by the respiratory route.^{105 166 228} In the US, N. meningitidis serogroups B, C, and Y cause most cases of meningococcal disease and serogroup W-135 causes a small percentage of cases.^{105 166 228 237} Serogroup B causes approximately 60% of US cases in infants and children <5 years of age;^{105 166} incidence of serogroup B disease in adults and adolescents 11–23 years of age is low (approximately 50–60 cases and 5–10 fatalities reported annually),³ but >80% of these cases are reported in older adolescents and adults 16–23 years of age.³ Although overall incidence of meningococcal disease in the US has been historically low during the last 10–15 years,^{3 105 166 228} overall case fatality rate has remained at 10–15% (even with anti-infective treatment)^{105 166 228} and fatality rate may be as high as 40% in those with meningococcemia.¹⁶⁶ In addition, long-term sequelae (e.g., hearing loss, neurologic disability, digit or limb amputations) reported in 11–20% of patients.^{105 166 228} While 98% of US cases of meningococcal disease are sporadic, localized outbreaks do occur and most outbreaks have been caused by serogroup B or C.^{166 228}

USPHS Advisory Committee on Immunization Practices (ACIP), AAP, and others recommend routine vaccination against meningococcal serogroup B infection in selected adults, adolescents, and children 10 through 25 years of age at increased risk for the disease because of certain chronic medical conditions (e.g., persistent complement component deficiencies in C3, C5–C9, properdin, factor H, or factor D; anatomic or functional asplenia, including sickle cell disease; individuals taking eculizumab).^{3 4 20 199 200} These experts also recommend routine immunization against meningococcal serogroup B infection in adults, adolescents, and children 10 through 25 years of age at increased risk because of potential exposure to N. meningitidis serogroup B (e.g., laboratory personnel routinely exposed to N. meningitidis, community or institutional outbreak of meningococcal serogroup B disease).^{3 4 20 199 200}

ACIP, AAP, and others state that data are insufficient to recommend routine vaccination against meningococcal serogroup B disease in all adolescents, but MenB vaccine may be considered in otherwise healthy adolescents and young adults 16 through 23 years of age to provide short-term protection against N. meningitidis serogroup B.^{3 20 199 200} If used in adolescents, the preferred age for MenB vaccination is 16 through 18 years of age^{3 20 199} since this maximizes likelihood that protection will last into highest age-related risk period in young adults (i.e., 18 through 23 years of age).³ Routine use of MenB vaccine not currently recommended in college freshmen who plan to live in dormitories.^{4 20 200}

Although safety and efficacy of MenB vaccine not established in adults ≥26 years of age,^{1 2} ACIP recommends routine vaccination against meningococcal serogroup B infection in selected adults ≥26 years of age^{† [off-label]} at increased risk because of certain chronic medical conditions (e.g., persistent complement component deficiencies in C3, C5–C9, properdin, factor H, or factor D; anatomic or functional asplenia, including sickle cell disease; individuals taking eculizumab).^{4 200} Routine immunization also is recommended in adults ≥26 years of age^{† [off-label]} at increased risk because of potential exposure to N. meningitidis serogroup B (e.g., laboratory personnel routinely exposed to N. meningitidis, community or institutional outbreaks of N. meningitidis serogroup B).^{4 200} ACIP states there is no theoretical difference in safety of MenB vaccine in adults in this age group compared with individuals 10 through 25 years of age.^{4 200}

MenB vaccine not recommended in infants and children <10 years of age^{† [off-label]}.^{4 199}

Routine vaccination against N. meningitidis serogroup B not recommended in military recruits.^{4 200}

Routine vaccination against N. meningitidis serogroup B not recommended in individuals who will be traveling to or residing in areas where N. meningitidis is highly endemic or epidemic (e.g., sub-Saharan Africa in area known as the “meningitis belt”);^{4 199 200} meningococcal disease in these areas usually caused by serogroups A, C, X, or W-135¹¹⁵ and not generally caused by serogroup B.^{4 199 200}

ACIP and AAP state that either MenB-4C or MenB-FHbp may be used, but the vaccines are not interchangeable.^{3 4 20 199 200} Current clinical data suggest that both MenB-4C and MenB-FHbp provide protection against disease caused by several strains of meningococcal serogroup B circulating in the US.^{1 2 3} However, effectiveness of the vaccines against diverse serogroup B strains has not been confirmed^{1 2} and neither vaccine is expected to provide protection again all meningococcal serogroup B strains.³

Meningococcal Group B Vaccine Dosage and Administration

Administration

Administer by IM injection.^{1 2}

Syncope (vasovagal or vasodepressor reaction; fainting) may occur following vaccination.^{1 134} Occurs most frequently in adolescents and young adults.¹³⁴ Have procedures in place to avoid falling injury and restore cerebral perfusion following syncope.^{1 134} Syncope and secondary injuries may be averted if vaccinees sit or lie down during and for 15 minutes after vaccination.¹³⁴ If syncope occurs, observe patient until symptoms resolve.¹³⁴

May be given simultaneously with other age-appropriate vaccines.^{3 4 20} When multiple vaccines are administered during a single health-care visit, give each parenteral vaccine with a different syringe and at different injection sites.^{3 4 20 134} Separate injection sites by at least 1 inch (if anatomically feasible) to allow appropriate attribution of any local adverse effects that may occur.¹³⁴

IM Administration

Administer IM in deltoid region of upper arm.^{1 2}

To ensure delivery of vaccine into muscle, make IM injections at a 90° angle to the skin using a needle length appropriate for the individual’s age and body mass, thickness of adipose tissue and muscle at injection site, and injection technique.¹³⁴

MenB-4C (Bexsero)

Immediately prior to administration, shake single-dose prefilled syringe well to obtain a homogeneous suspension.¹

Should appear as a white, opalescent suspension;¹ discard if it contains particulates, appears discolored, or cannot be resuspended.¹

MenB-FHbp (Trumenba)

Immediately prior to administration, shake single-dose prefilled syringe well to obtain a homogeneous white suspension.²

Discard if it contains particulates, appears discolored, or cannot be resuspended with thorough agitation.²

Do not mix with any other vaccine.²

Dosage

Dosing schedule (i.e., number and timing of doses) differ between MenB-4C and MenB-FHbp and may depend on the individual's risk of exposure and susceptibility to N. meningitidis serogroup B.^{1 2 6} Follow recommendations for specific vaccine used.^{1 2}

Data not available regarding interchangeability of MenB-4C and MenB-FHbp.^{1 2} ACIP and AAP state that MenB-4C and MenB-FHbp are not interchangeable;^{3 20 199 200} the MenB vaccine used for initial doses should be used to complete the vaccination series.^{3 20 199 200}

Pediatric Patients

Prevention of Meningococcal Group B Infection

Children and Adolescents 10 through 18 Years of Age (MenB-4C; Bexsero)

IM

Primary immunization consists of a series of 2 doses.^{1 3 4 20 199} Each dose consists of entire contents (0.5 mL) of commercially available single-dose prefilled syringe.¹

Children and adolescents 10 through18 years of age at increased risk because of certain medical conditions (e.g., persistent complement component deficiencies, anatomic or functional asplenia) or potential exposure (e.g., community or institutional outbreaks of meningococcal serogroup B disease): Give 2 doses at least 1 month apart.^{1 3 4 20 199}

Otherwise healthy adolescents: Give 2 doses at least 1 month apart to provide short-term protection.^{3 20 199} Preferred age for vaccination in such adolescents is 16 through 18 years of age.^{3 20 199}

Children and Adolescents 10 through 18 Years of Age (MenB-FHbp; Trumenba)

IM

Primary immunization consists of a series of 2 or 3 doses.^{2 3 4 6 20 199} Each dose consists of entire contents (0.5 mL) of commercially available single-dose prefilled syringe.²

Children and adolescents 10 through 18 years of age at increased risk because of certain medical conditions (e.g., persistent complement component deficiencies, anatomic or functional asplenia) or potential exposure (e.g., community or institutional outbreaks of meningococcal serogroup B disease): Use 3-dose regimen;^{2 3 4 6 20 199} give second dose 1–2 months after first dose and give third dose 6 months after first dose.^{2 3 4 6 20 199} If a 2-dose regimen is used in such patients, given second dose 6 months after first dose.²

Otherwise healthy adolescents: Use 2-dose regimen to provide short-term protection;^{6 20} give second dose 6 months after first dose.^{6 20} Preferred age for vaccination in such adolescents is 16 through 18 years of age.^{3 20 199}

Adults

Prevention of Meningococcal Group B Infection

Adults 19 through 25 Years of Age (MenB-4C; Bexsero)

IM

Primary immunization consists of a series of 2 doses.^{1 3 4 200} Each dose consists of entire contents (0.5 mL) of commercially available single-dose prefilled syringe.¹

Adults 19 through 25 years of age at increased risk because of certain medical conditions (e.g., persistent complement component deficiencies, anatomic or functional asplenia) or potential exposure (e.g., laboratory personnel routinely exposed to N. meningitidis, community or institutional outbreaks of meningococcal serogroup B disease): Give 2 doses at least 1 month apart.^{1 3 4 200}

Otherwise healthy adults 19 through 23 years of age: Give 2 doses at least 1 month apart to provide short-term protection.^{3 200}

Adults 19 through 25 Years of Age (MenB-FHbp; Trumenba)

IM

Primary immunization consists of a series of 2 or 3 doses.^{2 3 4 6 200} Each dose consists of entire contents (0.5 mL) of commercially available single-dose prefilled syringe.²

Adults 19 through 25 years of age at increased risk because of certain medical conditions (e.g., persistent complement component deficiencies, anatomic or functional asplenia) or potential exposure (e.g., laboratory personnel routinely exposed to N. meningitidis, community or institutional outbreaks of meningococcal serogroup B disease): Use a 3-dose regimen;^{2 3 4 6 200} give second dose 1–2 months after first dose and give third dose 6 months after first dose.^{2 3 4 6 200} If a 2-dose regimen is used in such patients, given second dose 6 months after first dose.²

Otherwise healthy adults 19 through 23 years of age: Use 2-dose regimen to provide short-term protection;⁶ give second dose 6 months after first dose.^{2 6}

Adults ≥26 Years of Age† [off-label] (MenB-4C; Bexsero)

IM

Primary immunization consists of a series of 2 doses.^{4 200} Each dose consists of entire contents (0.5 mL) of commercially available single-dose prefilled syringe.¹

Adults ≥26 years of age^† at increased risk because of certain medical conditions (e.g., persistent complement component deficiencies, anatomic or functional asplenia) or potential exposure (e.g., laboratory personnel routinely exposed to N. meningitidis, community or institutional outbreaks of meningococcal serogroup B disease): Give 2 doses at least 1 month apart.^{4 200}

Adults ≥26 Years of Age† (MenB-FHbp; Trumenba)

IM

Primary immunization consists of a series of 3 doses.^{4 6 200} Each dose consists of entire contents (0.5 mL) of commercially available single-dose prefilled syringe.²

Adults ≥26 years of age^† at increased risk because of certain medical conditions (e.g., persistent complement component deficiencies, anatomic or functional asplenia) or potential exposure (e.g., community or institutional outbreaks of meningococcal serogroup B disease): Use a 3-dose regimen;^{4 6 200} give second dose 1–2 months after first dose and give third dose 6 months after first dose.^{4 6 200}

Special Populations

Hepatic Impairment

No specific dosage recommendations.^{1 2}

Renal Impairment

No specific dosage recommendations.^{1 2}

Cautions for Meningococcal Group B Vaccine

Contraindications

• MenB-4C (Bexsero): Hypersensitivity, including severe allergic reactions, to any vaccine component or previous dose of the vaccine.¹

• MenB-FHbp (Trumenba): Severe allergic reaction after previous dose of the vaccine.²

Warnings/Precautions

Sensitivity Reactions

Hypersensitivity Reactions

MenB-4C: Hypersensitivity reactions (e.g., anaphylaxis, rash, eye swelling) reported.¹

Appropriate treatment (e.g., epinephrine) should be readily available in case an anaphylactic reaction occurs with MenB-4C or MenB-FHbp.^{1 2}

Latex Sensitivity

MenB-4C (Bexsero): Some packaging components (i.e., tip cap) contain natural rubber latex.¹ Some individuals may be hypersensitive to natural latex proteins.¹

ACIP states that vaccines supplied in vials or syringes containing dry natural rubber or natural rubber latex may be administered to individuals with latex allergies other than anaphylactic allergies (e.g., history of contact allergy to latex gloves), but should not be used in those with a history of severe (anaphylactic) allergy to latex unless the benefits of vaccination outweigh the risk of a potential allergic reaction.¹³⁴ Contact-type allergy is the most common type of latex sensitivity.¹³⁴

Syncope

Syncope reported following administration of vaccines, including MenB-4C.¹

Syncope occurs most frequently following vaccination in adolescents and young adults.^{105 134}

Observe vaccinee for 15 minutes following vaccination with MenB-4C or MenB-FHbp;^{105 134} have procedures in place to avoid falling injury and restore cerebral perfusion if syncope occurs.^{1 105 134} (See Administration under Dosage and Administration.)

Individuals with Altered Immunocompetence

Like other inactivated vaccines, MenB-4C or MenB-FHbp may be administered to individuals immunosuppressed as the result of disease or medical therapy.^{4 199 200} Consider possibility that immune response to the vaccine may be reduced.^{1 2}

Limitations of Vaccine Effectiveness

MenB vaccine (MenB-4C, MenB-FHbp) may not protect all vaccine recipients against meningococcal serogroup B infection.^{1 3}

MenB-4C and MenB-FHbp contain antigens representing several strains of meningococcal serogroup B circulating in the US.^{1 2 3} However, effectiveness of the vaccines against diverse serogroup B strains has not been confirmed;^{1 2} neither vaccine is expected to provide protection against all meningococcal serogroup B strains.³

Duration of Immunity

MenB-4C: In a study evaluating 2-dose regimen in adolescents 11 through 17 years of age (doses given 1, 2, or 6 months apart), 90–94% of vaccinees had composite response to all 3 N. meningitidis serogroup B strains tested at 1 month after second dose; 77–94% had serum bactericidal activity with human complement (hSBA) titer ≥1:4 against all 3 strains tested at 18–24 months after second dose.^{3 13}

MenB-FHbp: In a study evaluating 3-dose regimen, there was an initial rapid decline in antibodies after vaccination, followed by a flattening out of the antibody curve at approximately 6 months after third dose.³ At 48 months, >50% of vaccinees still had hSBA titers greater than or equal to lower limit of quantification against 3 of the 4 N. meningitidis serogroup B strains tested.³

Improper Storage and Handling

Improper storage or handling of vaccines may reduce vaccine potency resulting in reduced or inadequate immune response in vaccinees.¹³⁴

Inspect all vaccines upon delivery and monitor during storage to ensure that the appropriate temperature is maintained.¹³⁴

Do not administer vaccine that has been mishandled or has not been stored at the recommended temperature.¹³⁴ (See Storage under Stability.)

If there are concerns about mishandling, contact the manufacturer or state or local immunization or health departments for guidance on whether the vaccine is usable.¹³⁴

Specific Populations

Pregnancy

MenB-4C (Bexsero): Category B.¹ Pregnancy registry at 877-413-4759.¹

MenB-FHbp (Trumenba): Category B.²

Manufacturers state use MenB vaccine during pregnancy only if clearly needed.^{1 2}

ACIP states defer administration of MenB vaccine during pregnancy, unless the woman is at increased risk for meningococcal serogroup B disease and benefits of vaccination outweigh potential risks.³

Report any exposures to MenB vaccine that occur during pregnancy to the Vaccine Adverse Event Reporting System (VAERS) at 800-822-7967 or http:// www.vaers.hhs.gov/.^{1 2}

Lactation

Not known whether MenB vaccine is distributed into milk.^{1 2} Manufacturers recommend caution.^{1 2}

ACIP states defer administration of MenB vaccine in nursing women, unless the woman is at increased risk for meningococcal serogroup B disease and benefits of vaccination outweigh potential risks.³

Pediatric Use

MenB-4C (Bexsero): Safety and efficacy not established in infants and children <10 years of age.¹

MenB-FHbp (Trumenba): Safety and efficacy not established in infants and children <10 years of age.² In a clinical study in infants <12 months of age^† using a reduced dosage of MenB-FHbp, fever occurred in 90% of vaccinees.²

Geriatric Use

MenB-4C and MenB-FHbp: Safety and efficacy not established in adults ≥65 years of age.^{1 2}

Common Adverse Effects

MenB-4C: Injection site reactions (e.g., pain, induration, erythema), fatigue, headache, nausea, myalgia, arthralgia, fever.¹

MenB-FHbp: Injection site reactions (e.g., pain, swelling, erythema), fatigue, headache, vomiting, diarrhea, myalgia, arthralgia, chills, fever.²

Drug Interactions

Other Vaccines

Manufacturers state data are insufficient to date to evaluate concurrent use of MenB vaccine with other vaccines.^{1 2} Although specific studies may not be available,^{1 2} ACIP and AAP state that MenB vaccine may be given simultaneously with other age-appropriate vaccines;^{4 20} administer each parenteral vaccine using a different syringe and different injection site.^{3 20}

Specific Drugs

Stability

Storage

Solution, for IM Use

MenB-4C (Bexsero): 2–8°C;¹ protect from light.¹ Do not freeze;¹ if freezing occurs, discard vaccine.¹

MenB-FHbp (Trumenba): 2–8°C.² Store syringes horizontally (laying flat) to minimize redispersion time.² Do not freeze;² if freezing occurs, discard vaccine.²

Actions

• MenB-4C (Bexsero) contains 3 recombinant surface proteins (NadA, NHBA, FHbp) and outer membrane vesicles (OMV) containing outer membrane protein PorA (serosubtype P1.4) of N. meningitidis serogroup B.^{1 3} The 3 surface protein components are produced using recombinant DNA technology in Escherichia coli followed by column chromatography purification.¹ The OMV protein (PorA P1.4) is produced by fermentation of a strain of N. meningitidis that expresses PorA P1.4 followed by deoxycholate inactivation.¹

• MenB-FHbp (Trumenba) contains 2 recombinant lipidated FHbp antigens (FHbp A05 and FHbp B01) produced using recombinant DNA technology in E. coli followed by column chromatography purification.^{2 14}

• Antigens present in MenB vaccines stimulate active immunity to meningococcal serogroup B infection by promoting production of specific antibodies.^{1 2 3 11 14 15} These antibodies activate complement-mediated killing of meningococci to provide protection against infection by strains of N. meningitidis represented in the vaccine.^{1 2 3 11 14 15}

• Following IM administration of MenB vaccine (MenB-4C or MenB-FHbp), complement-mediated antibody response to the vaccine antigens is measured as serum bactericidal activity with human complement (hSBA).^{1 2 3 4 11 14} An hSBA titer of at least 4 (serum dilution of 1:4) in response to MenB vaccine antigens is generally accepted as correlating with protection against N. meningitidis serogroup B.^{11 15} However, susceptibility of N. meningitidis serogroup B to complement-mediated antibody-dependent killing following vaccination with a 2-dose regimen of MenB-4C or a 2- or 3-dose regimen of MenB-FHbp depends on the degree of similarity between the vaccine antigens and the invading strain of N. meningitidis serogroup B and the amount of antigen expressed on the surface of the invading strain.^{1 14}

Advice to Patients

• Prior to administration of each vaccine dose, provide a copy of the appropriate CDC Vaccine Information Statement (VIS) to the patient or patient’s parent or guardian (VISs are available at [Web]).^{1 2 5}

• Advise patient and/or patient’s parent or guardian of the risks and benefits of vaccination with MenB vaccine.^{1 2}

• Importance of completing vaccination series using the recommended number of doses of MenB-4C or MenB-FHbp, unless contraindicated.^{1 2}

• Advise patient and/or patient’s parent or guardian that MenB vaccine may not provide protection in all vaccinees.¹

• Advise patient and/or patient’s parent or guardian that fainting (sometimes resulting in falling with injury) reported following vaccination, especially in adolescents and young adults;^{1 105 134} patient should sit or lie down during and for 15 minutes after vaccine administration.^{1 105 134}

• Importance of informing clinicians of a history of allergic reactions to MenB vaccine, any vaccine component, or packaging component (e.g., latex).¹

• Importance of informing clinicians if any adverse reactions (including allergic reactions) occur with MenB vaccine.^{1 2} Clinicians or individuals can report any adverse reactions that occur following vaccination to VAERS at 800-822-7967 or [Web].^{1 2}

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, and any concomitant illnesses.^{1 2}

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.^{1 2}

• Importance of informing patients of other important precautionary information.^{1 2} (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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