Kimmel antibody response to group C polysaccharide in children and adults (Granoff et al 1998; MacDonald et al 1998; Danzig 2004). It has been posited that repeated stimulation of B cells with the T-cell independent plain polysaccharide vaccine results in terminal differentiation of B cells to pro- duce plasma cells and depletes the pool of speciﬁc B cells (Granoff and Pollard 2007). The serogroup B meningococcal polysaccharide is poorly immunogenic and the resulting IgG antibodies have poor complement bactericidal activity. In addition, the serogroup B capsular polysaccharide is structurally similar to a nerve cell molecule present in developing neural tissue and small amounts of adult tissue (Danzig 2004). Vaccines for serogroup B that utilize the outer membrane vesicle (OMV) of N. meningitidis are under trial in a number of countries (Borrow et al 2005). Their use is beyond the scope of this article. The United Kingdom (UK) experience with conjugate meningococcal C vaccine Polysaccharides conjugated to carrier proteins induce T-cell dependent immunity (Granoff 2004). In November, 1999, the UK initiated a program to vaccinate all children with conjugate meningococcal C vaccine. Two vaccine brands used CRM197 as the carrier protein (Wyeth and Novartis, Canada, QC) and one used tetanus toxoid (Baxter Biosci- ence, IL, USA) (Borrow and Miller 2006). The vaccine was given to infants at 2, 3, and 4 months of age, with a single dose catch-up to all children ages 1–18 years old and two doses for infants 5–11 months old (Borrow and Miller 2006). These vaccines were demonstrated to be immunogenic and efﬁcacious in infants, children, and adolescents. The number of cases of serogroup C IMD in adolescents 15–17 years old decreased by 76% from Jan 1 to Sept 30, 2000 compared with the corresponding period in 1999 and vaccine efﬁcacy was estimated at 97% in teenagers (Ramsay et al 2001). Cases of serogroup C IMD in toddlers decreased by 34% during this period, but vaccine efﬁcacy was estimated at 92% (Ramsay et al 2001). More than 1 year later, vaccine effectiveness decreased signiﬁcantly in infants 2–4 months at initial immu- nization while effectiveness in older children and especially adolescents persisted (Trotter et al 2004). The nasopharyngeal carriage of meningococcal serogroup C bacteria in students aged 15–17 years was found to decrease by 66% 1 year later (Maiden and Stuart 2002). The attack rate of serogroup C IMD subsequently decreased by 67% overall in un-immunized children and adolescents from July 2001 to June 2002 compared with July 1998 to June 1999 (Ramsay 742 et al 2003). Consequently, there is evidence of herd immunity in unvaccinated members of the population or those in whom antibody levels have waned if a high enough proportion of the population is vaccinated. Safety and efﬁcacy of the tetravalent meningococcal conjugate vaccine Three separate groups of 30 healthy US adults ages 18–55 years were given a single dose of tetravalent meningococcal conjugate vaccine containing either 1, 4, or 10 μg of each capsular polysaccharide conjugated to diphtheria toxoid. Twenty-eight days after immunization, the percentage of recipients with SBA titers of 8 was 100%, 89%–100%, 88%, and 91% for serogroups A, C, Y, and W-135, respec- tively (Campbell et al 2002). Mild to moderate local reactions such as injection site erythema and swelling occurred in over 50%–90% of subjects and in each dose group, 41%–50% reported at least one systemic reaction such as headache and malaise. One subject experienced severe pain, chills, and malaise with local tenderness and vomiting that resolved within 2 days (Campbell et al 2002). Another study random- ized over 800 adolescents (ages 11–18 years) to MPSV4 or the meningococcal conjugate vaccine containing 4 μg of capsular polysaccharide each from serogroups A, C, Y, W-135 (MCV4). Both vaccines were highly immunogenic to all four serogroups, although the MCV4 recipients reported more local reactions than the MPSV4 group (69% vs 30%) (Keyserling et al 2005). Follow-up at 3 years demonstrated persistence of SBA and booster responses to MCV4 consis- tent with immune memory that was not present in the MPSV4 group (Keyserling et al 2005). In January 2005, the US Food and Drug Administration (FDA) licensed Meningococcal Polysaccharide (serogroups A, C, Y, and W-135) Diphthe- ria Toxoid Conjugate Vaccine (MCV4, Menactra®, Sanoﬁ Pasteur, Inc., Swiftwater, PA, US) for the immunization of adolescents and adults aged 11–55 years age (Bilukha and Rosenstein 2005). A US study compared safety and immunogenicity of MCV4 with MPSV4 in 2- to 10-year-old children. The percentage of children with SBA titers 1/128 ranged from 81%–97% across the 4 serogroups in the MCV4 group versus 73%–93% for the MPSV4 group (Pichichero et al 2005). Mild to moderate local and systemic reactions of short duration were common and comparable in both groups (Pichichero et al 2005). A subgroup of children vac- cinated with MCV4 were given a challenge dose of MPSV4 23–36 months later. They demonstrated an increase in IgG Therapeutics and Clinical Risk Management 2008:4(4)