The Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention and the American Academy of Pediatrics approved updated recommendations for the use of quadravalent (serogroups A, C, W-135, and Y) meningococcal conjugate vaccines (Menactra [Sanofi Pasteur, Swiftwater, PA] and Menveo [Novartis, Basel, Switzerland]) in adolescents and in people at persistent high risk of meningococcal disease. The recommendations supplement previous Advisory Committee on Immunization Practices and American Academy of Pediatrics recommendations for meningococcal vaccinations. Data were reviewed pertaining to immunogenicity in high-risk groups, bactericidal antibody persistence after immunization, current epidemiology of meningococcal disease, meningococcal conjugate vaccine effectiveness, and cost-effectiveness of different strategies for vaccination of adolescents. This review prompted the following recommendations: (1) adolescents should be routinely immunized at 11 through 12 years of age and given a booster dose at 16 years of age; (2) adolescents who received their first dose at age 13 through 15 years should receive a booster at age 16 through 18 years or up to 5 years after their first dose; (3) adolescents who receive their first dose of meningococcal conjugate vaccine at or after 16 years of age do not need a booster dose; (4) a 2-dose primary series should be administered 2 months apart for those who are at increased risk of invasive meningococcal disease because of persistent complement component (eg, C5–C9, properdin, factor H, or factor D) deficiency (9 months through 54 years of age) or functional or anatomic asplenia (2–54 years of age) and for adolescents with HIV infection; and (5) a booster dose should be given 3 years after the primary series if the primary 2-dose series was given from 2 through 6 years of age and every 5 years for persons whose 2-dose primary series or booster dose was given at 7 years of age or older who are at risk of invasive meningococcal disease because of persistent component (eg, C5–C9, properdin, factor H, or factor D) deficiency or functional or anatomic asplenia.

Neisseria meningitidis is an important cause of invasive bacterial disease in infants, children, adolescents, and young adults. The highest rates occur in children younger than 1 year. Unlike infants in whom serogroup B meningococcus causes the majority of invasive disease, the majority of cases in adolescents and young adults in the United States are caused by serogroups that are included in available vaccines. Adolescents and young adults experience rates of meningococcal disease that exceed those of the general population.1  Increased risk begins at 14 years of age and persists through the age of 22 years (Fig 1).1 

In 2005, the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention and the American Academy of Pediatrics developed recommendations for the use of the quadrivalent meningococcal conjugate vaccine (MCV4) with the objective of protecting adolescents as well as young adults aged 16 through 21 years, the time at which meningococcal disease rates peak.2,,6  Recent information on persistence of antibodies and the occurrence of breakthrough cases indicates that this recommendation for administration of MCV4 at 11 through 12 years of age may not provide protection for more than 5 years or throughout the full period of highest risk.

Certain immunocompromising conditions predispose to invasive meningococcal infection, including persistent complement component (such as C5–C9, properdin, factor H, or factor D) deficiency, functional or anatomic asplenia, and HIV infection. These immunocompromising conditions may reduce immune response to the meningococcal conjugate vaccine or may require higher titers of antibody to provide protection. Thus, people with these conditions are likely to benefit from a 2-dose primary series.

In 2005, when the recommendation was made for routine administration of meningococcal vaccine to 11- through 12-year-olds,2,4  with catch-up immunization through 18 years of age, protective antibody concentrations were expected to persist for 10 years, through the period of increased vulnerability. Recent studies that evaluated antibody persistence after administration of MCV4 demonstrated that approximately 50% of persons vaccinated 5 years earlier will not have protective bactericidal antibody concentrations for serogroups C and Y (Table 1).7,,12  These serologic data demonstrated waning immunity 5 years after MCV4 administration, and serum antibody concentrations returned to levels similar to those detected in vaccine-naive individuals (Sanofi Pasteur [5-year follow-up of 11- to 18-year-olds at first dose], personal communication, sanfi provided slides with the data to the ACIP Meningococcal Working Group. Written communication/unpublished data.).

Additional data suggest that waning antibody concentrations result in increased susceptibility to meningococcal disease in older adolescents and young adults.13  Comparisons of the numbers of estimated annual cases of serogroup C and Y disease in the period before the vaccine recommendation (2000–2004) with those from post–vaccine-recommendation years (2005–2009) revealed a greater reduction in the number of cases among adolescents aged 11 through 14 years (74% reduction) when compared with older adolescents of aged 15 through 18 years (27% reduction).

A case-control study that evaluated vaccine effectiveness of the first licensed MCV4 (Menactra [Sanofi Pasteur, Swiftwater, PA]) noted a decrease in vaccine effectiveness with time since immunization.14  The overall vaccine effectiveness for adolescents immunized 0 to 5 years previously was 78.0% (95% confidence interval [CI]: 29%–93%). The effectiveness of the vaccine for persons vaccinated less than 1 year earlier, 1 year earlier, and 2 through 5 years earlier was 95% (95% CI: 10%–100%), 91% (95% CI: 10%–101%), and 58% (95% CI: 72%–89%), respectively. Although the 95% CIs around the point estimate were wide, the trend supports waning immunity. Data for vaccine effectiveness beyond 5 years since immunization are not available.

Between July 1, 2006, and October 31, 2010, the Centers for Disease Control and Prevention received 30 reports of serogroup C or Y invasive meningococcal disease in persons aged 15 through 22 years who had previously received a meningococcal conjugate vaccine; 12 of the 30 cases of meningococcal disease occurred in 2010. The mean age of people in these cases from 2010 was 18.2 years (range: 16–22 years). The mean time since they had received their meningococcal conjugate vaccine and the development of meningococcal disease was 3.25 years (range: 1.5–4.6 years). Five of these 12 people with breakthrough meningococcal disease had an underlying condition that might have affected their risk of meningococcal disease (Centers for Disease Control and Prevention, personal communication from Amanda Cohn MD, 2010).1 

Cases of breakthrough meningococcal disease in MCV4 recipients seem to have clinical manifestations similar to disease occurring in vaccine-naive persons.14,15  The lack of modification of illness suggests that an anamnestic immune response was not sufficient to modify disease severity. Recent data suggest that the memory response after meningococcal C conjugate vaccine is not rapid enough to protect against disease.15  The incubation period for invasive meningococcal disease is usually less than 3 days. After initial priming with monovalent meningococcal C (MenC) conjugate vaccine, a memory response after a booster dose is not measurable until 5 to 7 days after the booster.9 

Herd immunity seems to be important for long-term protection after widespread use of monovalent meningococcal C conjugate vaccine in the United Kingdom. Immunization coverage with MCV4 has been slow in the United States. In the 2009 National Immunization Survey-Teen, 53.6% of adolescents aged 13 through 17 years had received a dose of meningococcal vaccine.16  To date, there is no evidence that this level of uptake of a single dose of MCV4 provides herd immunity in the United States.

Two studies have assessed the serologic response after a booster dose of MCV4 (Menactra).7,14  When a booster dose was administered either 3 or 5 years after the first dose, the geometric mean titer elicited after the booster dose was substantially higher than that after the primary dose. This finding is consistent with expectations that the first dose of MCV4 primes the immune system and results in a strong response to the booster dose. Local and systemic reactions to the booster dose were comparable to reactions noted in persons who received a first dose. The duration of protective concentrations of antibody after a booster dose is not known. A booster dose administered at 16 through 18 years of age is expected to result in protective antibody concentrations through the age of 21 years.

The cost of a second dose of MCV4 in adolescents was considered in deliberations that led to the new recommendation. When using the cost-effectiveness measure of quality-adjusted life-years (QALYs), the 2-dose schedule had a lower cost per QALY than did the recommendation for a single dose given at 11 through 12 years of age, because the 2-dose series results in a greater reduction in the number of cases, morbidities, and mortalities attributable to invasive meningococcal disease.17  Another option was a single dose of MCV4 at 15 years of age. This had the lowest cost per QALY of the 3 options considered (no change in recommendation; single dose at 15 years of age; and 2 doses: at 11–12 years of age and a booster at 16 years of age).17  However, the cost per QALY for the single dose at 15 years of age and the 2-dose series at 11 and 16 years of age was not significantly different, and the 2-dose series resulted in fewer cases of invasive meningococcal disease and fewer deaths.17 

People with persistent complement component deficiency or properdin deficiency respond similarly to healthy children when immunized with the quadrivalent meningococcal polysaccharide vaccine (MPSV4). However, their antibodies wane more quickly than do those of healthy children. Antibody data from this population after administration of MCV4 are lacking. Maintaining high antibody concentrations is important for people with complement component deficiency, because higher antibody concentrations are needed for other clearance mechanisms, such as opsonophagocytosis, to kill meningococci.18,19 

Asplenic people achieve significantly lower geometric mean serum bactericidal activity than do healthy people immunized with monovalent meningococcal C conjugate vaccine. In 1 study, a protective antibody concentration was not achieved in 20% of asplenic people after vaccination.20  However, the percentage of those in whom protective antibody concentrations did not develop decreased to 7% when a booster dose was given 2 months later, which suggests that a booster dose can increase the proportion of asplenic people who have protective antibody concentrations and might be able to achieve higher circulating antibody concentrations and improve immunologic memory.

Although HIV-infected children may have an increased risk of meningococcal disease, the magnitude of the increased risk has not been established. MCV4 is not routinely recommended for HIV-infected children younger than 11 years. Response rates to MCV4 among HIV-infected adolescents are lower than those in healthy adolescents. In 1 study, seroconversion rates were significantly lower in adolescents with CD4+ T-lymphocyte percentages less than 15% or viral loads greater than 10 000 copies per mL.21 

A 2-dose primary series has not been studied in older children or adolescents. However, immunogenicity and safety of a 2-dose primary series of MCV4 with either Menactra or Menveo (Novartis, Basel, Switzerland) have been evaluated in infants and young children. Infants who received a 2-dose primary series of Menactra at 9 months and 12 through 15 months of age developed high antibody titers after the second dose. Data provided by Sanofi Pasteur has noted decreases in antibody concentrations for some pneumococcal serotypes when Menactra is administered at the same time as Prevnar 7 (Wyeth Pharmaceuticals, Philadelphia, PA) at 9 months and 12 to 15 months of age. The clinical significance of these decreased antibody concentrations is not clear. Because pneumococcal infections are a more common problem in children with asplenia (functional or anatomic), it would be prudent to provide age-appropriate pneumococcal conjugate vaccines to asplenic children and provide MCV4 after completion of the pneumococcal conjugate vaccine series. Adverse events after 2 doses of Menveo given 2 months apart to children 2 through 5 years of age had similar rates as after a single dose.22 

Routine immunization of adolescents with MCV4 is recommended at age 11 through 12 years along with a 1-time booster dose at 16 years of age (Table 2). For adolescents who receive their first dose of MCV4 at age 13 through 15 years, a 1-time booster should be administered, preferably at age 16 through 18 years, to provide additional protection during the period of increased risk. Adolescents who receive their first dose of MCV4 at or after 16 years of age do not need a booster dose. Immunization with the MCV4 vaccine is not recommended after 21 years of age in healthy people because of diminished risk of meningococcal disease after that age.

People with persistent complement deficiencies, functional or anatomic asplenia, or HIV infection should receive a 2-dose primary series given 2 months apart. Children aged 9 months or older with persistent complement deficiencies or functional or anatomic asplenia should receive the 2-dose primary series of MCV4. Children aged 2 years or older with functional or anatomic asplenia should receive the 2-dose primary series of MCV4. HIV-infected adolescents (>11 years) should receive a 2-dose primary series of MCV4 if they have not received any doses of MCV4 previously. HIV-infected children aged 2 through 10 years are likely to be at increased risk of meningococcal disease, but the risk is not as great as for invasive Streptococcus pneumoniae. MCV4 is not routinely recommended for HIV-infected children younger than 11 years. Providers may elect to give HIV-infected children aged 2 through 10 years a 2-dose primary series of MCV4. People with a history of complement component deficiency, asplenia, or HIV infection who have previously received a single dose of meningococcal conjugate vaccine as their primary dose should receive a second dose at least 2 months later. Booster doses should be given 3 years after the primary series if the primary 2-dose series was given from 2 through 6 years of age and 5 years after the primary series if the primary 2-dose series was given at 7 years of age or older. Boosters should then be given every 5 years. People who are at increased risk of meningococcal disease other than those with immunocompromising conditions (microbiologists who work routinely with N meningitidis or travelers to or residents of countries in which meningococcal disease is hyperendemic) should receive a single-dose primary series. If they remain at increased risk, a booster dose should be given 3 years later if the primary dose was given from 2 through 6 years of age and 5 years after the last dose if the previous dose was given at 7 years of age or older. If they continue to remain at risk, additional boosters should be given every 5 years.

Whenever feasible, the same brand of vaccine should be used for all doses of the vaccination series. Data are limited on the interchangeability of meningococcal vaccine products from different manufacturers. A small study revealed similar antibody responses when either Menactra or Menveo was given after a first dose of Menactra. If vaccination providers do not know or do not have available the brand of vaccine product previously administered, any product should be used to continue or complete the series. People who received quadrivalent meningococcal polysaccharide vaccine 5 or more years previously and remain at risk of meningococcal disease should be revaccinated with MCV4. There are no data to provide guidance as to how to address future needs for MCV4 vaccine in children who may have received vaccine products overseas that differ from products available in the United States. If these children remain at risk of meningococcal disease (healthy adolescent aged 11 years or older, complement deficiency, asplenia, etc), it would be prudent to provide MCV4 according to the recommendations for their risk group.

MCV4 is safe and immunogenic among nonpregnant women aged 11 through 55 years. No data are available on the safety of MCV4 during pregnancy. MCV4 should only be given to a pregnant woman if the benefit of providing vaccine during pregnancy outweighs the potential for risk. There is no contraindication to administering any dose of MCV4 to a woman who is breastfeeding.

Some states, secondary schools, colleges, or universities have policies that require immunization against meningococcal disease as a condition of enrollment. A single dose of MCV4 5 or fewer years before matriculation should be considered acceptable. A booster dose should be administered before matriculation if the adolescent was immunized more than 5 years previously.

Michael T. Brady, MD, Chairperson

Henry H. Bernstein, DO

Carrie L. Byington, MD

Kathryn M. Edwards, MD

Margaret C. Fisher, MD

Mary P. Glode, MD

Mary Anne Jackson, MD

Harry L. Keyserling, MD

David W. Kimberlin, MD

Yvonne A. Maldonado, MD

Walter A. Orenstein, MD

Gordon E. Schutze, MD

Rodney E. Willoughby, MD

Robert Bortolussi, MD

Canadian Paediatric Society

Marc A. Fischer, MD

Centers for Disease Control and Prevention

Bruce Gellin, MD

National Vaccine Program Office

Richard L. Gorman, MD

National Institutes of Health

Lucia Lee, MD

Food and Drug Administration

R. Douglas Pratt, MD

Food and Drug Administration

Jane Seward, MBBS, MPH

Centers for Disease Control and Prevention

Jeffrey R. Starke, MD

American Thoracic Society

Jack Swanson, MD

Committee on Practice Ambulatory Medicine

Tina Q. Tan, MD

Pediatric Infectious Diseases Society

Carol J. Baker, MD

Red Book Associate Editor

Sarah S. Long, MD

Red Book Associate Editor

H. Cody Meissner, MD

Red Book Associate Editor

Larry K. Pickering, MD

Red Book Editor

Lorry G. Rubin, MD

Jennifer Frantz, MPH

This document is copyrighted and is property of the American Academy of Pediatrics and its Board of Directors. All authors have filed conflict of interest statements with the American Academy of Pediatrics. Any conflicts have been resolved through a process approved by the Board of Directors. The American Academy of Pediatrics has neither solicited nor accepted any commercial involvement in the development of the content of this publication.

All policy statements from the American Academy of Pediatrics automatically expire 5 years after publication unless reaffirmed, revised, or retired at or before that time.

MCV4

quadrivalent meningococcal conjugate vaccine

CI

confidence interval

1.
Centers for Disease Control and Prevention
.
Updated recommendations for use of meningococcal conjugate vaccines: Advisory Committee on Immunization Practices (ACIP), 2010
.
MMWR Morb Mortal Wkly Rep
.
2011
;
60
(
3
):
72
76
2.
Bilukha
OO
,
Rosenstein
N
;
National Center for Infectious Diseases, Centers for Disease Control and Prevention
.
Prevention and control of meningococcal disease: recommendations of the Advisory Committee on Immunization Practices (ACIP)
.
MMWR Recomm Rep
.
2005
;
54
(
RR-7
):
1
21
3.
Centers for Disease Control and Prevention
.
Updated recommendation from the Advisory Committee on Immunization Practices (ACIP) for revaccination of persons at prolonged increased risk for meningococcal disease
.
MMWR Morb Mortal Wkly Rep
.
2009
;
58
(
37
):
1042
1043
4.
American Academy of Pediatrics, Committee on Infectious Diseases
.
Prevention and control of meningococcal disease: recommendations for use of meningococcal vaccines in pediatric patients
.
Pediatrics
.
2005
;
116
(
2
):
496
505
5.
American Academy of Pediatrics, Committee on Infectious Diseases
.
Meningococcal disease prevention and control strategies for practice-based physicians (addendum: recommendations for college students)
.
Pediatrics
.
2000
;
106
(
6
):
1500
1504
6.
American Academy of Pediatrics, Committee on Infectious Diseases; Canadian Paediatric Society, Infectious Diseases and Immunization Committee
.
Meningococcal disease prevention and control strategies for practice-based physicians
.
Pediatrics
.
1996
;
97
(
3
):
404
412
7.
Vu
DM
,
Welsch
JA
,
Zuno-Mitchell
P
,
Dela Cruz
JV
,
Granoff
DM
.
Antibody persistence 3 years after immunization of adolescents with quadrivalent meningococcal conjugate vaccine
.
J Infect Dis
.
2006
;
193
(
6
):
821
828
8.
Gill
CJ
,
Baxter
R
,
Anemona
A
,
Ciavarro
G
,
Dull
P
.
Persistence of immune responses after a single dose of Novartis meningococcal serogroup A, C, W-135 and Y CRM-197 conjugate vaccine (Menveo) or Menactra among healthy adolescents
.
Hum Vaccin
.
2010
;
6
(
11
):
881
887
9.
Snape
M
,
Kelly
D
,
Salt
P
, et al
.
Serogroup C meningococcal glycoconjugate vaccine in adolescents: persistence of bactericidal antibodies and kinetics of the immune response to a booster vaccine more than 3 years after immunization
.
Clin Infect Dis
.
2006
;
43
(
11
):
1387
1394
10.
Perrett
KP
,
Winter
AP
,
Kibwana
E
, et al
.
Antibody persistence after serogroup C meningococcal conjugate immunization of United Kingdom primary-school children in 1999–2000 and response to a booster: a phase 4 clinical trial
.
Clin Infect Dis
.
2010
;
50
(
12
):
1601
1610
11.
Snape
MD
,
Kelly
DF
,
Green
B
,
Moxon
ER
,
Borrow
R
,
Pollard
AJ
.
Lack of serum bactericidal activity in preschool children two years after a single dose of serogroup C meningococcal polysaccharide-protein conjugate vaccine
.
Pediatr Infect Dis J
.
2005
;
24
(
2
):
128
131
12.
Cohn
A
.
Centers for Disease Control and Prevention, Advisory Committee on Immunization Practices
.
Proceedings of the Advisory Committee on Immunization Practices (ACIP) meeting
,
Atlanta
.
June 24, 2009
13.
Macneil
JR
,
Cohn
AC
,
Zell
ER
,
Schmink
S
,
Miller
E
,
Clark
T
,
Messonnier
NE
;
Active Bacterial Core surveillance (ABCs) Team and MeningNet Surveillance Partners
.
Early estimate of the effectiveness of quadravalent meningococcal vaccine
.
Pediatr Infect Dis J
.
2011
;
30
(
6
):
451
455
14.
Cohn
A
.
Centers for Disease Control and Prevention, Advisory Committee on Immunization Practices
.
Proceedings of the Advisory Committee on Immunization Practices (ACIP) meeting
,
Atlanta
.
October 27, 2010
15.
Auckland
C
,
Gray
S
,
Borrow
R
, et al
.
Clinical and immunologic risk factors for meningococcal C conjugate vaccine failure in the United Kingdom
.
J Infect Dis
.
2006
;
194
(
12
):
1745
1752
16.
Rand
CM
,
Schaffer
SJ
,
Humiston
SG
, et al
.
Patient-provider communication and human papillomavirus vaccine acceptance
.
Clin Pediatr (Phila)
.
2011
;
50
(
2
):
106
113
17.
Ortega-Sanchez
I
.
Cost-effectiveness of Meningococcal Vaccination Strategies for Adolescents in the United States
.
Atlanta, GA
:
Advisory Committee on Immunization Practices, Centers for Disease Control and Prevention
;
2010
. . Accessed March 29, 2011
18.
Platonov
AE
,
Vershinina
IV
,
Kuijper
EJ
,
Borrow
R
,
Käyhty
H
.
Long term effects of vaccination of patients deficient in a late complement component with a tetravalent meningococcal polysaccharide vaccine
.
Vaccine
.
2003
;
21
(
27–30
):
4437
4447
19.
Fijen
CA
,
Kuijper
EJ
,
Drogari-Apiranthitou
M
,
Van Leeuwen
Y
,
Daha
MR
,
Dankert
J
.
Protection against meningococcal serogroup ACYW disease in complement-deficient individuals vaccinated with the tetravalent meningococcal capsular polysaccharide vaccine
.
Clin Exp Immunol
.
1998
;
114
(
3
):
362
369
20.
Balmer
P
,
Falconer
M
,
McDonald
P
, et al
.
Immune response to meningococcal serogroup C conjugate vaccine in asplenic individuals
.
Infect Immun
.
2004
;
72
(
1
):
332
337
21.
Siberry
GK
,
Williams
PL
,
Lujan-Zilbermann
J
, et al
;
IMPAACT P1065 Protocol Team
.
Phase I/II, open-label trial of safety and immunogenicity of meningococcal (groups A, C, Y and W-135) polysaccharide diphtheria toxoids conjugate vaccine in human immunodeficiency virus-infected adolescents
.
Pediatr Infect Dis J
.
2010
;
29
(
5
):
391
396
22.
Halperin
S
,
Gupta
A
,
Jeanfreau
R
, et al
.
Comparison of the safety immunogenicity of an investigational and a licensed quadrivalent meningococcal conjugate vaccine in children 2–10 years of age
.
Vaccine
.
2010
;
28
(
50
):
7865
7872