Meningococcal vaccination in children and adults

INTRODUCTION — Meningococcal disease is a devastating infection, an important cause of meningitis, sepsis, and, less often, pneumonia, pericarditis, and septic arthritis; Neisseria meningitidis tends to strike young, previously well individuals and can progress to death in a matter of hours. Survivors may have serious long-term sequelae (eg, loss of limbs, hearing loss, neurocognitive dysfunction).

The use of meningococcal vaccines to prevent meningococcal disease in children and adults will be discussed here. The microbiology, epidemiology, clinical features, diagnosis, treatment, and prevention of meningococcal infections are discussed separately:

●(See "Microbiology and pathobiology of Neisseria meningitidis".)

●(See "Epidemiology of Neisseria meningitidis infection".)

●(See "Clinical manifestations of meningococcal infection".)

●(See "Diagnosis of meningococcal infection".)

●(See "Treatment and prevention of meningococcal infection".)

AVAILABLE VACCINE FORMULATIONS — All available formulations of meningococcal vaccine are inactivated.

●Quadrivalent vaccines (serogroups A, C, W, and Y)

•Formulations in the United States – Available quadrivalent meningococcal conjugate vaccine (MenACWY) formulations in the United States include [1]:

-Meningococcal groups A, C, W, and Y oligosaccharide diphtheria CRM197 conjugate vaccine (MenACWY-CRM, Menveo), which was licensed in 2010. There are two presentations of MenACWY-CRM [2]:

A two-vial presentation, which requires reconstitution and is licensed for use in individuals two months through 55 years of age.

A one-vial presentation, which does not require reconstitution and is licensed for use in individuals 10 through 55 years of age.

-Meningococcal groups A, C, W, and Y polysaccharide tetanus toxoid conjugate vaccine (MenACWY-TT, MenQuadfi), which was licensed in 2020 and is approved for individuals ≥2 years of age.

Meningococcal groups A, C, W, and Y polysaccharide diphtheria toxoid conjugate vaccine (MenACWY-D, Menactra) was licensed in 2005 for individuals nine months through 55 years of age. It was discontinued in 2022 [3].

•Formulations outside of the United States – In addition to Menveo and MenQuadfi, quadrivalent meningococcal vaccines available outside the United States include [4]:

-Meningococcal groups A, C, W, and Y polysaccharide tetanus toxoid conjugate vaccine (Men-C-ACYW-TT, Nimenrix), which appears to have immunogenicity and safety similar to Menveo [5-7].

-Quadrivalent polysaccharide vaccines (unconjugated), which are available in limited international markets and were generally used for outbreak response and travelers [8]. The quadrivalent meningococcal polysaccharide vaccine (Menomune, MPSV4), previously available in the United States and elsewhere, was discontinued in 2017 [9].

●Monovalent vaccines – Available monovalent vaccines include:

•Serogroup A – Serogroup A meningococcal polysaccharide-tetanus toxoid conjugate vaccine (PsA-TT, MenAfriVac) is used in Africa [10,11] to control serogroup A epidemics and disease.

•Serogroup B – Two meningococcal serogroup B vaccine formulations (MenB-FHbp [Trumenba] and MenB-4C [Bexsero]) were licensed in the United States in 2014 and 2015 for use in individuals 10 through 25 years of age [1] and are recommended in groups at high risk for meningococcal disease.

MenB vaccines are also used in various age groups in other countries, including in Europe, Australia, Canada (MenB-fHBP [Trumenba] and 4CMenB [Bexsero]), and the United Kingdom [4,12,13]. As an example, MenB-4C is used in the United Kingdom and Europe in infants and young children [13].

•Serogroup C – Meningococcal serogroup C conjugate vaccine formulations (eg, Men-C-C-CRM [Menjugate], Men-C-C-TT [NeisVac-C]) are used in Europe, Canada, and other countries [4,12].

●Other formulations – Other available meningococcal vaccines outside the United States include [14,15]:

•Bivalent serogroups A and C polysaccharide vaccine

•Combination Haemophilus influenzae type b and N. meningitidis serogroup C vaccine (HibMecC)

A pentavalent conjugate vaccine (NmCV-5) targeting the A, C, W, Y, and X serogroups has been developed but has not yet been licensed for use. In a randomized trial of healthy 2- to 29-year-olds in Gambia and Mali, this vaccine was found to have similar immunogenicity to the MenACWY-D vaccine for the four serotypes they had in common [16]. The NmCV-5 vaccine also elicited immune responses to serogroup X. No safety concerns were evident.

INDICATIONS AND SCHEDULES IN THE UNITED STATES — In the United States, vaccination to prevent meningococcal disease is routinely recommended for adolescents and young adults (table 1). It is also recommended for persons ≥2 months of age who are at increased risk for meningococcal disease (algorithm 1 and table 2A-B) [1].

Our approach to meningococcal vaccination is generally consistent with recommendations from the United States Advisory Committee on Immunization Practices (ACIP) and the American Academy of Pediatrics (AAP) [1,17]. Some of the recommendations in our approach are considered off-label (eg, repeated booster doses, use of meningococcal vaccines outside the licensed age groups).

Routine immunization of adolescents and young adults

Quadrivalent meningococcal conjugate vaccine

●Preferred schedule – For healthy adolescents age 11 through 18 years, we recommend routine immunization with MenACWY, (MenACWY-CRM [Menveo] or MenACWY-TT [MenQuadfi]). Routine immunization of adolescents has been associated with decreased incidence of meningococcal disease in adolescents [18].

The recommended schedule is as follows (table 1) [1]:

•First dose at age 11 through 12 years

•Booster dose at age 16 years

The booster dose is necessary because the antibody response wanes within five years [19-22]. Individuals immunized at age 11 or 12 years may have decreased protective immunity by age 16 through 21 years, when their risk of disease is greatest. Although the same vaccine formulation is preferred for all doses, the available quadrivalent meningococcal conjugate vaccines are interchangeable in persons ≥2 years of age [1].

This schedule is appropriate for children who received MenACWY before age 10 years (eg, because of an outbreak or for travel). Those who received MenACWY at age 10 years do not need a dose at age 11 through 12 years but should receive a booster dose at age 16 years.

●Catch-up schedule – Adolescents who receive the first dose at age 13 through 15 years should receive a booster dose at age 16 through 18 years; the booster dose can be administered at any time ≥8 weeks after the first dose.

Adolescents who receive their first dose at ≥16 years of age do not require a booster dose unless they become at increased risk for meningococcal disease (eg, travel to an endemic area, undergo splenectomy); the booster dose should be administered ≥5 years after the previous dose; the antibody response to MenACWY wanes within five years [19-22]. (See 'Target groups' below.)

Persons age 19 through 21 years who did not receive a dose at ≥16 years of age should receive a single dose of MenACWY (even if they received a dose at age 11 through 12 years). This is particularly important for those who are going to attend college and is applicable to other congregate living settings. College students ≤21 years of age should have a documented dose of MenACWY ≤5 years before enrollment [1]. (See 'Age greater than or equal to 2 years and increased risk of exposure' below.)

●Effectiveness – MenACWY are effective in preventing meningococcal disease in adolescents and young adults in the first years after immunization, but protection decreases over time, necessitating the booster dose. In a case-control study after licensure, the overall effectiveness of MenACWY-D (Menactra) in preventing meningococcal disease was 69 percent (95% CI 51-80 percent) within eight years of vaccination [23]. Effectiveness waned from approximately 80 percent one year after vaccination, to 70 percent one to three years after vaccination, to 60 percent three to eight years after vaccination.

Although data regarding the effectiveness of MenACWY-CRM (Menveo) and MenACWY-TT (MenQuadfi) are lacking, the immunogenicity of MenACWY-CRM is similar to MenACWY-D [24]. MenACWY-TT is highly immunogenic and elicits a booster response when administered to adolescents and adults who received MenACWY-D or MenACWY-CRM [25-28].

The effectiveness of routine adolescent immunization is demonstrated by the continuing decline in the average annual incidence of meningococcal disease among adolescents and young adults after MenACWY vaccination was added to the routine adolescent immunization schedule in 2005 (from 0.57 to 0.19 per 100,000 among those age 11 to 15 years and from 1.0 to 0.56 per 100,000 among those age 16 through 22 years) and by further decline after the booster dose was recommended in 2010 (from 0.19 to 0.05 per 100,000 among those age 11 to 15 years and from 0.56 to 0.23 per 100,000 among those age 16 through 22 years) [18].

Although repeat immunization after five years has minimal adverse effects, data about the long-term duration of the response to the booster dose are limited [1,19,25-27,29].

Serogroup B meningococcal vaccine — For most healthy adolescents and young adults (age 16 through 23 years) in the United States, particularly those who are going to attend college, we suggest immunization with serogroup B meningococcal vaccine given the seriousness of meningococcal disease and the efficacy/effectiveness and safety of the available vaccine formulations [30-33]. The preferred age for vaccination is 16 through 18 years of age (eg, at the time of the MenACWY booster dose) (table 1) [1]. (See "Clinical manifestations of meningococcal infection", section on 'Meningitis and acute meningococcemia' and 'Serogroup B vaccines' below.)

Our suggestion for immunization differs from that of the ACIP, which encourages shared clinical decision-making for persons age 16 through 23 years of age because of the low incidence of serogroup B meningococcal disease in this age group in the United States (average annual incidence of 0.17 cases per 100,000 population) [1,34]. (See "Clinical manifestations of meningococcal infection", section on 'Meningitis and acute meningococcemia' and 'Serogroup B vaccines' below.)

Immunization of persons at increased risk — For persons at risk, meningococcal vaccine schedules vary with age, risk factor, previous immunization history, and vaccine formulation (table 2A-B) [1]. (See 'Age greater than or equal to 2 years and immunodeficiency that increases risk' below and 'Age greater than or equal to 2 years and increased risk of exposure' below.)

Target groups — Persons at increased risk for meningococcal disease may be loosely categorized into two groups: those with an immunodeficiency that increases the risk of meningococcal disease and those with increased risk of exposure to N. meningitidis (algorithm 1). Persons in each group may be targeted for both MenACWY and serogroup B meningococcal vaccines (MenB), MenACWY only, or MenB only (during an outbreak) (table 2A-C).

●Immunodeficiencies – Immunodeficiencies that increase the risk of meningococcal disease include (see "Epidemiology of Neisseria meningitidis infection"):

•Anatomic or functional asplenia (including sickle cell disease) [35,36]; the timing of meningococcal immunization for patients undergoing splenectomy is discussed separately. (See "Prevention of infection in patients with impaired splenic function", section on 'Timing of vaccination'.)

•HIV infection. (See "Immunizations in persons with HIV", section on 'Meningococcal vaccine'.)

•Complement component deficiency (eg, properdin, factor D, factor H, and late complement component [C5 through C9]). (See "Inherited disorders of the complement system", section on 'C5-C9 deficiency'.)

•Use of C5 inhibitors (eg, eculizumab, ravulizumab). Meningococcal vaccines should be administered ≥2 weeks before the first dose of complement inhibitor, unless the risk for delaying complement therapy outweighs the risk for developing meningococcal disease.

●Increased risk of exposure – Persons at increased risk of exposure to meningococcus include:

•Microbiologists routinely exposed to N. meningitidis.

•Persons who travel to or live in countries where meningococcal disease is hyperendemic or epidemic (eg, the meningitis belt of sub-Saharan Africa during the dry season [December through June] (figure 1), Hajj pilgrimage). Individuals who received routine vaccination with MenACWY may need a booster if it has been more than five years since their last dose.

•Those exposed during an outbreak caused by serogroup A, B, C, W, or Y.

•Previously unimmunized or underimmunized military recruits.

•Previously unimmunized or underimmunized college freshmen living in residence halls.

In addition, some experts may discuss administration of MenACWY to children older than six weeks who had complicated serotype B meningococcal infection but are not in one of the above target groups. The administration of MenACWY to such children may help prevent future infections with other serogroups.

Age 2 through 23 months — For children age 2 through 23 months, the schedules for primary and booster doses of MenACWY vary with age, risk factor, previous immunization history, and vaccine formulation (table 2A) [1]. Although MenB is not licensed for use in children <10 years of age in the United States [1], MenB-4C (Bexsero) has been used in this population in other countries, and some experts choose to vaccinate children at substantial risk for meningococcal disease (eg, those receiving C5 inhibitors) with MenB-4C (Bexsero). In this scenario, MenB-4C should be used rather than MenB-FHbp (Trumenba) because there are less data with MenB-FHbp and it was originally abandoned in infants because of reactogenicity [37]. Data describing the use of MenB in children <10 years of age are presented below. (See 'Immunogenicity and effectiveness' below.)

●Age 2 through 6 months (any risk factor) – For infants age 2 through 6 months who are at increased risk of meningococcal disease, MenACWY-CRM (Menveo) is the only available quadrivalent meningococcal conjugate vaccine.

The primary immunization series consists of [1]:

•Three doses, ≥8 weeks apart.

•A fourth dose at age 12 months.

●Age 7 through 8 months (any risk factor) – For infants age 7 through 8 months who are at increased risk of meningococcal disease, MenACWY-CRM (Menveo) is the only available quadrivalent meningococcal conjugate vaccine.

The primary immunization series consists of [1]:

•Two doses of MenACWY-CRM (Menveo), ≥12 weeks apart; the second dose should be given at age ≥12 months.

●Age 9 through 23 months

•Anatomic or functional asplenia or HIV infection – For children age 9 through 23 months with anatomic or functional asplenia or HIV, the primary immunization series consists of [1]:

-Two doses of MenACWY-CRM (Menveo), ≥12 weeks apart; the second dose should be given at age ≥12 months.

•Complement component deficiency, use of C5 inhibitors, or travel – For children age 9 through 23 months of age with complement component deficiency, treated with C5 inhibitors, or who travel to or live in countries where meningococcal disease is hyperendemic or epidemic, the primary immunization series consists of [1]:

-Two doses of MenACWY-CRM (Menveo), ≥12 weeks apart; the second dose should be given at age ≥12 months

Age greater than or equal to 2 years and immunodeficiency that increases risk — The ACIP recommends meningococcal immunization for previously unimmunized persons ≥2 years of age with an immunodeficiency that increases the risk of meningococcal disease, including (table 2B) [1]:

●Anatomic or functional asplenia (including sickle cell disease)

●HIV infection

●Complement component deficiency (eg, properdin, factor D, factor H, and late complement component [C5 through C9])

●Use of C5 inhibitors (eg, eculizumab, ravulizumab)

The ACIP makes no specific recommendations for other immunocompromised persons (eg, related to immunosuppressive medications).

●MenACWY primary series – For previously unvaccinated immunocompromised persons at increased risk for meningococcal disease, the primary MenACWY immunization series consists of two doses of any MenACWY vaccine (MenACWY-CRM [Menveo] or MenACWY-TT [MenQuadfi]), ≥8 weeks apart (table 2B) [1].

MenACWY-CRM and MenACWY-TT can be given at any time in relation to routine vaccines [38,39]. (See 'Administration in relation to other vaccines' below.)

Healthy persons ≥2 years of age who received a single dose of MenACWY (eg, for travel) and subsequently develop a condition that requires a two-dose primary series (eg, asplenia, HIV, complement component deficiency) should receive a second dose to complete the primary series as soon as possible, provided that the two doses are ≥8 weeks apart [1].

●MenACWY booster doses – Immunocompromised persons who remain at increased risk of meningococcal disease should receive booster doses of MenACWY [1]. The booster schedule varies with age (table 2B):

•Age <7 years – Initial booster three years after completion of the primary series and every five years thereafter.

•Age ≥7 years – Booster doses every five years.

If MenACWY-TT (MenQuadfi) is not available for those ≥56 years of age, MenACWY-CRM (Menveo) may be used off-label [1].

●MenB primary series – Persons ≥10 years of age with anatomic or functional asplenia, complement component deficiency, and use of C5 inhibitors should be immunized against serogroup B meningococcal disease (table 2B) [1]. (See 'Vaccine schedules' below.)

Although MenB is not licensed for use in children <10 years of age in the United States [1], MenB-4C (Bexsero) has been used in this population in other countries, and some experts choose to vaccinate children at substantial risk for meningococcal disease (eg, those receiving C5 inhibitors) with MenB-4C. In this scenario, MenB-4C should be used rather than MenB-FHbp (Trumenba) because there are less data with MenB-FHbp and it was originally abandoned in infants because of reactogenicity [37]. Data describing the use of MenB in children <10 years of age are presented below. (See 'Immunogenicity and effectiveness' below.)

The ACIP makes no recommendation for MenB in persons with HIV unless it is otherwise indicated (eg, age 16 through 23 years based on shared decision-making, outbreak). Most meningococcal cases reported among persons living with HIV infection in the United States are caused by serogroups C, W, or Y [40].

●Men B booster doses – Persons ≥10 years of age with anatomic or functional asplenia, complement component deficiency, or use of C5 inhibitors should receive booster doses of the same MenB formulation that was given for the primary series one year after completion of the primary series and every two to three years thereafter (table 2B) [1]. Antibody titers to MenB vaccines begin to wane within one to two years of immunization. (See 'Immunogenicity and effectiveness' below.)

Age greater than or equal to 2 years and increased risk of exposure — The ACIP recommends meningococcal immunization for previously unimmunized persons who are at increased risk for exposure to meningococcal disease, including microbiologists who routinely work with N. meningitidis, college freshmen, military recruits, persons who travel to or live in countries where meningococcal disease is hyperendemic or epidemic (table 2B) [1]. (See "Epidemiology of Neisseria meningitidis infection".)

●MenACWY primary series – For immunocompetent persons ≥2 years of age who are at increased risk of exposure to meningococcal disease, the MenACWY primary series consists of a single dose of any MenACWY (MenACWY-CRM [Menveo] or MenACWY-TT [MenQuadfi]). MenACWY-CRM and MenACWY-TT may be given at any time in relation to DTaP. (See 'Administration in relation to other vaccines' below.)

College students who did not receive a dose of MenACWY at ≥16 years of age or whose most recent dose of MenACWY was ≥5 years ago should receive a single dose of any MenACWY vaccine [1].

●MenACWY booster doses

•Microbiologists – Microbiologists who continue to work routinely with N. meningitidis should receive a booster dose of MenACWY every five years. If MenACWY-TT (MenQuadfi) is not available, for those ≥56 years of age, MenACWY-CRM (Menveo) may be used off-label [1].

•College students – MenACWY booster doses are not recommended for college students unless otherwise indicated (eg, they require treatment with a C5 inhibitor) [1].

•Military recruits – In the United States, the Department of Defense determines the need for booster doses for military recruits according to their assignments [1].

•Travel – Persons who plan to travel to an endemic region and previously completed a primary series of MenACWY (eg, for an outbreak) should receive a booster dose [1]:

-Three years after the primary series for those age <7 years

-Five years after the primary series for those age ≥7 years

If the increased risk remains (eg, longstanding employment overseas or child of caregiver with longstanding employment overseas), persons should receive a booster dose every five years thereafter.

●MenB primary series and booster doses

•Microbiologists – Microbiologists who routinely work with N. meningitidis should be immunized against serogroup B meningococcal disease (table 2B) [1]. If they continue to work with N. meningitidis, they should receive a booster dose with the same formulation of MenB that was used for the primary series one year after completion of the primary series and every two to three years thereafter.

•College students – We suggest MenB for college students aged 16 to 23 years, as discussed above. (See 'Serogroup B meningococcal vaccine' above.)

•Military recruits and travelers – MenB is not routinely recommended for military recruits or travelers unless it is otherwise indicated (eg, during an outbreak, age 16 through 23 years) [1].

Outbreak control — Meningococcal vaccination is used to reduce the number of secondary cases when an outbreak of meningococcal disease is caused by a vaccine serogroup (eg, A, C, W, Y, or B) [41]. The goal of vaccination is to achieve a level of herd protection in the target population, which reduces spread of infection via the nasopharyngeal route [42].

The decision to vaccinate during an outbreak is determined on a case-by-case basis in consultation with public health officials. We follow the guidance of the United States Centers for Disease Control and Prevention [41]:

●Organization-based outbreak – When cases are linked by a common affiliation (eg, university, school, correctional facility) other than a geographic location, vaccination is typically warranted when there are two to three outbreak-associated cases during a three-month period.

●Community-based outbreak – When cases are linked by a shared, geographically defined community (eg, neighborhood, town) or population (eg, men who have sex with men) with shared characteristics without affiliation to a specific organization, vaccination is indicated if there are multiple outbreak-associated cases with an incidence of meningococcal disease that is above the expected incidence in that community during a three-month period. The expected incidence can be determined by:

•A similar three-month time period in previous years

•Annual incidence in the previous three to five years (if community incidence is low or unstable)

•State or national incidence (if community incidence has historically been near zero)

The choice of vaccine depends upon the serogroup responsible for the outbreak. Dosing recommendations are presented in the table (table 2C).

A number of regional vaccination campaigns undertaken to control outbreaks of meningococcus serogroup B infection have been associated with decreased rates of infection [43-45]. Serogroup B meningococcal vaccines appear to provide limited protection in the setting of outbreaks caused by strains not included in the vaccine (ie, strains with capsular B antigen but differing noncapsular proteins, including outer membrane vesicles) [46-49].

Serogroup C conjugate vaccination has also been observed to be effective in control of an emerging epidemic [50,51].

INDICATIONS AND SCHEDULES IN OTHER COUNTRIES — The approach to meningococcal vaccination varies by country [52].

●Europe – Schedules for countries in Europe are available through the European Centre for Disease Prevention and Control [53] and the World Health Organization (WHO) [12].

Most cases of meningococcal disease in Europe are caused by serogroups B, W, and C; vaccination against these serogroups is part of the routine immunization schedule in many European countries [54,55].

●Other regions – Schedules for countries in other regions are available through the WHO [12].

Recommendations issued by the WHO for meningococcal vaccination in Africa include large-scale meningococcal vaccination for individuals 1 to 29 years of age in countries with high (>10 cases/100,000 population/year) and intermediate (2 to 10 cases/100,000 population/year) endemic rates [11]. In African countries where the incidence is lower (<2 cases/100,000 population/year), meningococcal vaccination is warranted for groups at known risk of meningococcal exposure.

Quadrivalent meningococcal conjugate vaccines may be used for routine vaccination; monovalent vaccines (serogroup A or C) may be used to control outbreaks. Serogroup B vaccines have not been widely available but are increasingly used in Europe, North America, South America, and Australasia.

VACCINE INFORMATION

MenACWY — Quadrivalent meningococcal conjugate vaccines (MenACWY) are inactivated vaccines that consist of capsular polysaccharide antigens from serogroups A, C, W, and Y conjugated to a protein carrier (eg, CRM197 [MenACWY-CRM, Menveo] or tetanus toxoid [MenACWY-TT, MenQuadfi]).

Compared with polysaccharide vaccines without a protein carrier, conjugation to the protein carrier elicits a T cell-dependent memory response, which results in improved primary response to vaccination in infants, a strong anamnestic response at re-exposure, and reduced nasopharyngeal carriage (herd protection) compared with polysaccharide vaccines without a carrier protein (which are no longer available in the United States but are available in other countries) [4,14,56,57].

Immunogenicity — When the incidence of meningococcal disease is low, as in the United States, immune correlates of protection (eg, serum bactericidal antibody activity) are used to estimate vaccine efficacy [1]. The immunogenicity of licensed quadrivalent meningococcal conjugate vaccines has been evaluated in various age groups.

In a multicenter randomized trial that compared MenACWY-D (Menactra) with quadrivalent meningococcal polysaccharide vaccine (MPSV4) in healthy adolescents, 80 to 97 percent of participants in both groups had fourfold or greater increases in serum bactericidal antibody [56]. At the three-year follow-up, recipients of MenACWY-D had persistent antibody and booster response to a second dose of MenACWY-D. The immunogenicities of MenACWY-CRM (Menveo) and MenACWY-TT (MenQuadfi) are comparable to that of MenACWY-D [24-28].

In a similar randomized trial that compared MenACWY-D with MPSV4 in children 2 to 10 years of age, MenACWY-D elicited higher antibody titers for all four serogroups and antibody persisted for 23 to 36 months [57,58]. Other randomized trials have demonstrated that MenACWY-CRM is immunogenic [59], and the immunogenicity is similar to that of MenACWY-D [60].

In three randomized trials including >4900 infants immunized with MenACWY-D, 86 to 100 percent achieved protective serum antibody titers to serogroups A, C, W, and Y 30 days after vaccination [61]. In another study, children who were two to three years of age at the time of initial MenACWY-D vaccination had persistence of bactericidal antibody 23 to 36 months later [58]. MenACWY-CRM has also been evaluated in randomized trials and found to be immunogenic in infants [62-66].

Effectiveness — The effectiveness of MenACWY is discussed above. (See 'Quadrivalent meningococcal conjugate vaccine' above.)

Contraindications and precautions

●Contraindications – Severe allergic reaction to a previous dose or to any component of the vaccine is a contraindication to MenACWY-CRM (Menveo) and MenACWY-TT (MenQuadfi) [24,27,67]. This encompasses severe allergic reaction to any vaccine that contains diphtheria toxoid or CRM197 for MenACWY-CRM and severe allergic reaction to any vaccine that contains tetanus toxoid for MenACWY-TT.

●Precautions – Precautions are conditions that may increase the risk of adverse reactions, diminish the immune response, or make it difficult to differentiate between a clinical manifestation of the condition and a vaccine adverse effect (eg, fever, seizure) [68]. In persons with precautions, the risks and benefits of immunization (versus postponing the immunization) should be considered on a case-by-case basis.

Moderate to severe illness with or without fever is a precaution for administration of all vaccines. For infants younger than nine months, preterm birth is a precaution for MenACWY-CRM [68]. The Advisory Committee on Immunization Practices (ACIP) does not consider a history of Guillain-Barré syndrome to be a precaution for administration of quadrivalent meningococcal conjugate vaccines [1], although it is included as a precaution in the prescribing information [24,27,67].

Syncope following immunization appears to be more common among adolescents and young adults than other age groups [69]. Having the recipient sit or lie down for 15 minutes after vaccination may prevent syncopal episodes and secondary injuries. If syncope occurs, patients should be observed until symptoms resolve. (See "Standard immunizations for children and adolescents: Overview", section on 'Local and systemic reactions'.)

Dose and route — MenACWY-CRM (Menveo) and MenACWY-TT (MenQuadfi) are all administered intramuscularly (IM) at a dose of 0.5 mL. Although the same vaccine formulation is preferred for all doses, the available quadrivalent meningococcal vaccines are interchangeable [1].

For the two-vial presentation of MenACWY-CRM, the lyophilized MenA component must be reconstituted with the liquid MenCWY component immediately before administration. If the liquid MenCWY component is inadvertently administered alone without the lyophilized MenA component, revaccination is not required for persons in the United States who are not planning to travel internationally, since serogroup A meningococcal disease is rarely reported in the United States [1]. However, revaccination as soon as is feasible is necessary if the person plans to travel internationally, particularly to a region where serogroup A meningococcal disease is endemic, or when vaccination is required (eg, the Hajj pilgrimage).

For patients who inadvertently receive MenACWY subcutaneously rather than IM, ACIP guidance indicates that the dose need not be repeated [70].

Administration in relation to other vaccines

●Routine administration – For routine administration in otherwise healthy adolescents and young adults, MenACWY can be administered at the same visit as other routinely recommended vaccines (eg, tetanus and reduced diphtheria toxoids and acellular pertussis vaccine [Tdap], human papillomavirus vaccine) [1,71,72].

Simultaneous administration is supported by a randomized trial including more than 1300 adolescents immunized with Tdap and MenACWY-D (Menactra), which noted similar safety and immune responses against meningococcus, pertussis, diphtheria, and tetanus, whether the vaccines were administered on the same day or 30 days apart [71]. Similarly, in an observational study, the risk of adverse events was comparably low whether Tdap and MenACWY-D were administered simultaneously or sequentially [72].

●For individuals at increased risk – For individuals at increased risk, MenACWY-CRM (Menveo) and MenACWY-TT (MenQuadfi) may be administered at any time in relation to other vaccines [1,38,39,63].

Adverse events

●Common adverse events – The most commonly reported adverse reactions to quadrivalent meningococcal conjugate vaccines are erythema, injection site swelling, myalgia, fever, fatigue, and headache [1] among adolescents and adults. Irritability and drowsiness are the most common systemic adverse events among infants and children.

Syncope, sometimes associated with severe injury, has been reported in postmarketing surveillance for MenACWY-D (Menactra) and MenACWY-CRM (Menveo) [1]. Syncope may occur after any immunization and is more common in adolescents than in other age groups [69]. (See "Allergic reactions to vaccines", section on 'Vasovagal reactions'.)

●Unproven association with Guillain-Barré syndrome – Although cases of Guillain-Barré syndrome (GBS) were reported following receipt of MenACWY-D (Menactra) in early postmarketing surveillance, and a previous history of GBS was listed as a precaution for MenACWY-D in the package insert [73-75], subsequent large safety studies did not demonstrate an increased risk of GBS after MenACWY-D [76,77].

No cases of GBS have been reported in association with MenACWY-CRM (Menveo); postmarketing surveillance for MenACWY-TT (MenQuadfi) is limited.

The clinical features and diagnosis of GBS are discussed separately. (See "Guillain-Barré syndrome in children: Epidemiology, clinical features, and diagnosis" and "Guillain-Barré syndrome in adults: Pathogenesis, clinical features, and diagnosis".)

In the United States, adverse events such as GBS after quadrivalent meningococcal conjugate vaccine should be reported to the Vaccine Adverse Event Reporting System (VAERS; www.vaers.hhs.gov or 1-800-822-7967; fax 1-877-721-0366). (See "Guillain-Barré syndrome in children: Epidemiology, clinical features, and diagnosis" and "Guillain-Barré syndrome in adults: Pathogenesis, clinical features, and diagnosis".)

Serogroup B vaccines — Two serogroup B meningococcal vaccines (MenB-FHbp [Trumenba], MenB-4C [Bexsero]) are available for use in the United States, Europe, and other countries [1,4,15].

Vaccine schedules — Serogroup B meningococcal vaccines are not interchangeable. The same vaccine formulation should be given for all doses. Valid completion of a series for individuals who receive different MenB vaccine formulations is discussed below. (See 'Receipt of different MenB formulations' below.)

●Schedules in the United States

•MenB-4C (Bexsero) – For routine vaccination of healthy individuals and persons at increased risk for serogroup B meningococcal disease, the primary series for MenB-4C consists of two doses, separated by ≥1 month [1].

Individuals at increased risk for serogroup B meningococcal disease may require booster doses (table 2B). (See 'Age greater than or equal to 2 years and immunodeficiency that increases risk' above and 'Age greater than or equal to 2 years and increased risk of exposure' above.)

•MenB-FHbp (Trumenba) – The schedule for the primary series of MenB-FHbp varies with the indication [1]:

-For routine vaccination of healthy individuals – Two doses, separated by ≥6 months; if the second dose is administered <6 months after the first dose, a third dose should be given ≥4 months after the second.

-For individuals at increased risk for serogroup B meningococcal disease and during outbreaks – Three doses: at 0, 1 to 2, and 6 months; if the third dose is administered <4 months after the second dose, a fourth dose should be given ≥4 months after the third dose.

Individuals at increased risk for serogroup B meningococcal disease may require booster doses (table 2B). (See 'Age greater than or equal to 2 years and immunodeficiency that increases risk' above and 'Age greater than or equal to 2 years and increased risk of exposure' above.)

●Schedule in other countries – The recommended schedule for MenB vaccines in countries outside the United States is available through the European Centre for Disease Prevention and Control [53] and the World Health Organization (WHO) [12].

Immunogenicity and effectiveness — In randomized trials in adolescents and young adults, MenB vaccines are immunogenic and well tolerated [30-32]. Following an appropriate primary series, immunogenic responses were achieved in >80 percent of adolescents and young adults [30,31]. For both MenB-FHbp (Trumenba) and MenB-4C (Bexsero), antibody titers after initial primary series decline one to two years after vaccination [78-81]. Booster doses elicit a robust immune response that appears to last for at least two years [1,81]. In contrast to the MenACWY conjugate vaccines, MenB vaccines do not appear to substantially reduce disease causing meningococcal carriage in adolescents and young adults [82,83].

MenB vaccines have also been demonstrated to be immunogenic, effective, and well tolerated in healthy infants and children and in children with asplenia or splenic dysfunction [13,32,84-91]. Although they are not licensed in the United States for children <10 years of age, MenB-4C is licensed in Europe and other countries for children ≥2 months of age and is used either routinely or for at-risk children [53,92]. In a case-control study from Spain where MenB-4C is available for private purchase, complete vaccination with MenB-4C was 71 percent effective against invasive serogroup B meningococcal disease in children younger than 60 months; receipt of ≥1 dose was 64 percent effective [90]. In studies of MenB-4C from other countries using differing vaccine schedules, vaccine effectiveness ranges from 53 to 94 percent [13,86,93]. MenB-4C protection against meningococcal serogroup B disease appears to be sustained for at least two years [13,90].

Because MenB-4C contains antigens that are shared with non-B meningococcal serogroups, it may also provide indirect protection against non-B meningococcal serogroups [49,90,94,95]. In the case-control study from Spain described above, complete vaccination with MenB-4C was 76 percent effective against invasive meningococcal disease caused by any serogroup in children younger than 60 months; receipt of ≥1 dose was 68 percent effective [90]. In addition, in observational studies, administration of MenB-4C has been associated with protection against Neisseria gonorrhoeae [96-99].

Receipt of different MenB formulations — Serogroup B meningococcal vaccines are not interchangeable. For patients who inadvertently receive two doses using different MenB formulations, either MenB-FHbp (Trumenba) or MenB-4C (Bexsero) should be chosen to complete the series. The patient should receive another dose at the appropriate interval for that product and ≥4 weeks after the most recent dose of MenB [1]. The chosen product should be used to complete the primary series and for any necessary booster doses. As examples, for persons without a high-risk condition:

●If MenB-FHbp is chosen, the second (final) dose of MenB-FHbp should be given ≥6 months after the previous dose of MenB-FHbp and ≥4 weeks after the invalid dose of MenB-4C.

●If MenB-4C is chosen, the second (final dose) of MenB-4C should be given one month after the previous dose of MenB-4C and ≥4 weeks after the invalid dose of MenB-FHbp.

Other aspects of administration

●Contraindications and precautions – Severe allergic reaction to a previous dose or to any component is a contraindication to MenB [68,100,101].

Precautions for administration for MenB include [68,100]:

•Moderate to severe illness with or without fever

•Pregnancy (see "Immunizations during pregnancy")

•Latex sensitivity (for MenB-4C [Bexsero]) because the tip caps of some prefilled MenB-4C syringes contain natural rubber latex

●Dose and route – MenB are administered intramuscularly (IM) at a dose of 0.5 mL.

●Administration with other vaccines – MenB may be given at the same visit with quadrivalent meningococcal conjugate vaccines and other vaccines routinely administered to adolescents and young adults [1]. They should be administered at different anatomic sites if feasible.

●Adverse events – The most common adverse reactions with MenB include pain at the injection site, fatigue, headache, myalgia, and arthralgia [1].

Serogroup A vaccines — Serogroup A historically was the most common cause of epidemic meningococcal disease in the meningitis belt of sub-Saharan Africa. (See "Epidemiology of Neisseria meningitidis infection".)

Serogroup A meningococcal polysaccharide-tetanus toxoid conjugate vaccine (PsA-TT, MenAfriVac) has been highly effective in preventing serogroup A invasive meningococcal disease and eliminating carriage in sub-Saharan Africa [10,102-105]. In a vaccination campaign in Burkina Faso that included more than 11 million people ages 1 to 29 years, PsA-TT was associated with decreased rates of meningitis, elimination of epidemics, and elimination of pharyngeal carriage (in vaccinated and unvaccinated individuals) for at least 13 months [104,105].

In a randomized trial, PsA-TT elicited a stronger immune response than the quadrivalent polysaccharide vaccine (PsACWY) [106]. The duration of protective immune response is age dependent. Among children one to four years of age, a decline in serum bactericidal antibody titers at six to eight years after immunization has been observed, suggesting that a booster dose eight years after the initial dose is warranted [107]. The antibody responses in individuals older than four years persist for longer periods.

Serogroup C vaccines — Vaccination against serogroup C is part of the routine immunization schedule in many European countries. Some countries continue to use monovalent serogroup C vaccines while others have switched to quadrivalent vaccines for routine immunization, depending upon local epidemiology [108].

In a meta-analysis of four observational studies in individuals age two months to 24 years, the effectiveness of conjugate meningococcal serogroup C vaccines in preventing invasive meningococcal disease was 87 percent (95% CI 77-93) [82].

A randomized trial including more than 180 infants demonstrated that the meningococcal C conjugate vaccine is safe and immunogenic when given with other routinely administered vaccines at two, three, and four months of age [109]. A subsequent study including 250 children aged 6 to 12 years demonstrated that antibody wanes, leaving inadequate seroprotection in most individuals, but a booster was highly effective [110].

Substantial reductions in the incidence of serogroup C disease after large-scale vaccination campaigns have been observed in several countries; these reductions have been due to individual seroprotection as well as herd immunity [42,50,51,111-118].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Immunizations in children and adolescents" and "Society guideline links: Immunizations in adults" and "Society guideline links: Meningococcal infection" and "Society guideline links: Travel medicine".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Vaccines for adults (The Basics)" and "Patient education: Vaccines for children age 7 to 18 years (The Basics)")

●Beyond the Basics topics (see "Patient education: Vaccines for adults (Beyond the Basics)" and "Patient education: Vaccines for children age 7 to 18 years (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Introduction – Meningococcal disease is a devastating infection; Neisseria meningitidis tends to strike young, previously well individuals and can progress to death in a matter of hours. Survivors may have serious long-term sequelae (eg, loss of limbs, hearing loss, neurocognitive dysfunction). (See 'Introduction' above.)

●Available vaccine formulations – Available meningococcal vaccine formulations include quadrivalent meningococcal conjugate vaccines for serogroups A, C, W, and Y (MenACWY) and monovalent vaccines (eg, serogroup B). All available formulations are inactivated. (See 'Available vaccine formulations' above.)

●Approach to vaccination in the United States – The approach to vaccination depends upon the predominant serogroup in a geographic area, as well as the patient's age and risk of developing meningococcal infection. MenACWY and serogroup B meningococcal vaccines (MenB) are immunogenic and associated with a very low risk of serious adverse reactions. (See 'Indications and schedules in the United States' above and 'Vaccine information' above.)

•Healthy adolescents and young adults

-For healthy adolescents age 11 through 18 years in the United States, we recommend routine immunization with MenACWY (Grade 1B). Routine immunization of adolescents has been associated with decreased incidence of meningococcal disease (table 1).

-For most healthy adolescents and young adults (age 16 through 23 years), we also suggest routine immunization with MenB (Grade 2C). Although the absolute incidence of meningococcal disease is low, invasive meningococcal disease is associated with serious long-term sequelae. (See 'Routine immunization of adolescents and young adults' above.)

•Persons at increased risk – For other patients ≥2 months of age who are at increased risk for meningococcal disease in the United States, our approach to immunization with MenACWY and MenB depends upon age, the intensity of exposure risk (eg, microbiologists, college students, those who travel to hyperendemic areas), and the type of immunodeficiency (algorithm 1 and table 2A-B). As examples:

-For persons with anatomic or functional asplenia (including sickle cell disease), complement component deficiency, and use of C5 inhibitors, we recommend MenACWY (Grade 1B); for those ≥10 years of age in this group, we also provide MenB vaccine. (See 'Immunization of persons at increased risk' above.)

-For persons with HIV, we suggest MenACWY immunization (Grade 2C). (See "Immunizations in persons with HIV", section on 'Meningococcal vaccine'.)

•Meningococcal outbreak – Meningococcal vaccination is used to reduce the number of secondary cases when an outbreak of meningococcal disease is caused by a vaccine serogroup (eg, A, C, W, Y, or B). The decision to vaccinate during an outbreak is determined on a case-by-case basis in consultation with public health officials. The choice of vaccine depends upon the serogroup responsible for the outbreak (table 2C). (See 'Outbreak control' above.)

●Approach to vaccination outside the United States – Outside of the United States, the approach to vaccination varies by country. Schedules are available through the European Centre for Disease Prevention and Control and the World Health Organization (WHO). (See 'Indications and schedules in other countries' above.)

●Vaccine administration

•MenACWY – For MenACWY, the same vaccine formulation is preferred for all doses of the primary series; however, if this is not possible, MenACWY-CRM (Menveo) and MenACWY-TT (MenQuadfi) are considered interchangeable for persons ≥2 years of age. MenACWY can be given at any time in relation to other routinely administered vaccines. (See 'MenACWY' above.)

•Serogroup B vaccines – Serogroup B meningococcal vaccines (MenB) are not interchangeable; the same formulation must be used for all primary and booster doses. MenB can be given at any time in relation to other routine immunizations. (See 'Serogroup B vaccines' above.)