Inching Toward a Serogroup B Meningococcal Vaccine for Infants
In the past decade, the introduction of meningococcal conjugate vaccines has led to substantial reductions in meningococcal disease. Monovalent serogroup C vaccines have virtually eliminated serogroup C disease from the United Kingdom and other countries, and serogroup A, C, W, and Y vaccines have reduced disease among adolescents in the United States.1,2 In 2010 and 2011, Burkina Faso, Mali, Niger, and part of Nigeria introduced serogroup A conjugate vaccine, which may eliminate epidemic meningitis from the meningitis belt of Africa. These accomplishments have been dampened by the lack of effective serogroup B meningococcal vaccines. Serogroup B meningococcal disease causes substantial morbidity and mortality globally, especially in young infants.3- 5 Serogroup B disease can be devastating; 5% to 10% of children with the disease do not survive and another 10% to 20% experience long-term sequelae such as hearing loss, limb loss, and neurologic deficits.5 Disease burden is lower in the United States than in other countries; incidence of serogroup B disease is 0.16 per 100 000 population but 3.08 per 100 000 population among infants younger than 12 months.4 In contrast, incidence of serogroup B disease in several countries in Europe, including the United Kingdom, is about 10-fold that in the United States.3
[Show abstract] [Hide abstract] ABSTRACT: Background: College students living in residential halls are at increased risk of meningococcal disease. Unlike that for serogroups prevented by quadrivalent meningococcal vaccines, public health response to outbreaks of serogroup B meningococcal disease is limited by lack of a US licensed vaccine. Methods: In March 2010, we investigated a prolonged outbreak of serogroup B disease associated with a university. In addition to case ascertainment, molecular typing of isolates was performed to characterize the outbreak. We conducted a matched case-control study to examine risk factors for serogroup B disease. Five controls per case, matched by college year, were randomly selected. Participants completed a risk factor questionnaire. Data were analyzed using conditional logistic regression. Results: Between January 2008 and November 2010, we identified 13 meningococcal disease cases (7 confirmed, 4 probable, and 2 suspected) involving 10 university students and 3 university-linked persons. One student died. Ten cases were determined to be serogroup B. Isolates from 6 confirmed cases had an indistinguishable pulsed-field gel electrophoresis pattern and belonged to sequence type 269, clonal complex 269. Factors significantly associated with disease were Greek society membership (matched odds ratio [mOR], 15.0; P = .03), >1 kissing partner (mOR, 13.66; P = .03), and attending bars (mOR, 8.06; P = .04). Conclusions: The outbreak was associated with a novel serogroup B strain (CC269) and risk factors were indicative of increased social mixing. Control measures were appropriate but limited by lack of vaccine. Understanding serogroup B transmission in college and other settings will help inform use of serogroup B vaccines currently under consideration for licensure.0Comments 20Citations
- "If serogroup B outbreaks have a relatively protracted " natural history " compared to serogroup C outbreaks, applying the same outbreak definitions for serogroup C as thresholds for public health interventions might not be appropriate. Serogroup B vaccines [19, 20] under development have potential to control serogroup B outbreaks on college campuses, but these vaccines will likely require a multidose schedule to be effective [21, 22] . Further understanding serogroup B transmission and risk factors in different populations and settings, such as through nasopharyngeal carriage studies, will inform strategies for sero group B vaccine use. "
[Show abstract] [Hide abstract] ABSTRACT: Aim: To describe the dynamics in the incidence of childhood invasive meningococcal disease (IMD) in Israel during a 22-year period (1989-2010). Methods: A longitudinal prospective surveillance in all 27 medical centers with pediatric services in Israel. All cases of children <15 years old with positive blood/cerebrospinal fluid (CSF) culture for Neisseria meningitidis were reported. Demographic, clinical, and bacteriological data were recorded. Meningococcal vaccine was not routinely given to Israeli children during the study period. Results: The mean age ± standard deviation (SD) among the 743 cases was 40.7 ± 40.2 months. The mean yearly incidence/100,000 was 2.0 ± 0.8. Age-specific incidences were 8.7 ± 2.8, 2.9 ± 1.5, and 0.8 ± 0.5 for children <1, 1-4, and >4 years old, respectively. The overall incidence decreased significantly from 3.7 in 1989 to 1.5 in 2010. Meningitis constituted 69.2 % of all cases. The most common serogroups were: B (76.9 %), C (10.9 %), Y (8.0 %), and W(135) (2.9 %). 78.6 % of all serogroup B isolates were from children <5 years old (p < 0.01). Serogroup C was found mainly in children ≥5 years old (63.4 %). The case fatality rates (CFRs) for children <1, 1-4, >4 years old, and the total study population were 9.2, 12.3, 7.7, and 9.9 %, respectively. CFRs were higher for children without meningitis (14.9 %) compared to children with meningitis (7.9 %) (p < 0.01). Conclusions: Overall, and for serogroups B and W135, childhood IMD rates decreased significantly in Israel during the study period, without routine vaccine usage. The most common serogroup in all age groups was B, which was most prevalent in children <5 years old. No change in the trend of the overall CFR was noted during the study period.0Comments 4Citations
- "Thus, the development of meningococcal vaccines for use in infants (particularly those \1 year of age) is essential . In this regard, the development of a broadly protective serogroup B vaccine that is safe and immunogenic in young infants during recent years and the anticipated licensure of this vaccine means that, for the first time, vaccines to prevent all five of the serogroups causing the most meningococcal disease worldwide will be available . "
- [Show abstract] [Hide abstract] ABSTRACT: Meningococcal disease is a life-threatening invasive infection (mainly septicemia and meningitis) that occurs as epidemic or sporadic cases. The causative agent, Neisseria men-ingitidis or meningococcus, is a capsulated Gram-negative bacterium. Current vaccines are prepared from the capsular polysaccharides (that also determine serogroups) and are available against strains of serogroups A, C, Y, and W-135 that show variable distribution worldwide. Plain polysaccharide vaccines were first used and subsequently conjugate vaccines with enhanced immunogenicity were introduced. The capsular polysaccharide of meningococcal serogroup B is poorly immunogenic due to similarity to the human neural cells adhesion molecule. Tailor-made, strain-specific vaccines have been developed to control localized and clonal outbreaks due to meningococci of serogroup B but no "universal" vaccine is yet available. This unmet medical need was recently overcome using several subcapsular proteins to allow broad range coverage of strains and to reduce the risk of escape variants due to genetic diversity of the meningococ-cus. Several vaccines are under development that target major or minor surface proteins. One vaccine (Bexsero ® ; Novartis), under registration, is a multicomponent recombinant vaccine that showed an acceptable safety profile and covers around 80% of the currently circulating serogroup B isolates. However, its reactogenicity in infants seems to be high and the long term persistence of the immune response needs to be determined. Its activity on carriage, and there-fore transmission, is under evaluation. Indirect protection is expected through restricting strain circulation and acquisition. This vaccine covers the circulating strains according to the presence of the targeted antigens in the circulating isolates as well as to their levels of expression. The coverage rate should therefore be updated and the surveillance of circulating isolates should include typing schemes for the antigens of the future vaccines. We review the recent available data for these upcoming protein-based vaccines and particularly Bexsero ® .0Comments 2Citations