Quadrivalent Meningococcal Polysaccharide Vaccine Research Articles

1157. Immune Persistence and Booster Response of a Quadrivalent Meningococcal Conjugate Vaccine (MenACYW-TT) 5 Years After Primary Vaccination of Adults ≥59 Years of Age

Abstract Background MenACYW-TT (MenQuadfi®, Sanofi) is a quadrivalent (serogroups A, C, W, and Y) meningococcal tetanus toxoid conjugate vaccine. It is approved for use in persons aged ≥2 years in the US and persons aged ≥1 year in Europe and certain other countries; trials in infants as young as 6 weeks are ongoing. The second stage of a 2-stage study of MenACYW-TT, reported herein, evaluated immune persistence among older adults who received primary vaccination with either quadrivalent meningococcal polysaccharide vaccine (MSPV4) or MenACYW-TT five years earlier at age ≥ 56 years. The immunogenicity and safety of a MenACYW-TT booster dose given to this population were also evaluated. Methods This was a Phase 3, 2-stage, randomized, open-label, multi-center study (NCT04142242) of adults aged ≥59 years who participated in previous studies of MenACYW-TT vs MPSV4 (NCT01732627 and NCT02842866). The study was conducted in the US and Puerto Rico. Immune persistence and response were assessed with a serum bactericidal assay using human complement (hSBA). Safety data were collected for up to 30 days after booster vaccination. All analyses were descriptive. Results Of the initial study population (N=471), 70 adults participated in Stage II of the study. At 5 years post-primary vaccination, seroprotection (hSBA ≥ 1:8) rates (SPRs) and hSBA geometric mean titers (GMTs) declined in both MenACYW-TT- and MPSV4-primed subjects, with SPRs and hSBA GMTs for serogroups A, C, W, and Y trending higher in MenACYW-TT- vs MPSV4-primed subjects (Table 1). Thirty days after booster vaccination, hSBA GMTs and SPRs increased from pre-booster for all serogroups and were, along with seroresponse rates, higher in MenACYW-TT-primed subjects compared to MPSV4-primed subjects (Table 2). Rates of AEs following booster vaccination were similar regardless of priming vaccine. No safety concerns were identified. Conclusion Five years after primary vaccination, immune persistence tended to be greater for MenACYW-TT vs MPSV4. A MenACYW-TT booster was well tolerated and immunogenic in adults ≥ 61 years, when administered 5 years after primary vaccination with either MPSV4 or MenACYW-TT. Disclosures Corwin A. Robertson, MD, MPH, FACP, Sanofi: Sanofi employee|Sanofi: Sanofi's Employee|Sanofi: Stocks/Bonds Katherine Galarza, MD, Sanofi: Sanofi employee|Sanofi: Stocks/Bonds Alexandre Selmani, PhD, Sanofi: Sanofi employee|Sanofi: Stocks/Bonds Philipp Oster, MD, Sanofi: Sanofi employee

Safety and immunogenicity of quadrivalent meningococcal polysaccharide vaccine (MPV ACYW135) compared with quadrivalent meningococcal conjugate vaccine (Menactra®) in Malian children

ABSTRACT Affordable, polyvalent meningococcal vaccines are needed for use in emergency reactive immunization campaigns. A phase IV randomized, observer-blind, controlled study compared the safety and immunogenicity of a quadrivalent meningococcal polysaccharide vaccine (MPV-4, MPV ACYW135) and quadrivalent meningococcal ACWY conjugate vaccine (MCV-4, Menactra®). Healthy, 2- to 10-year-old children in Bamako, Mali, were randomized 1:1 to receive one dose of MPV-4 or MCV-4. Safety outcomes were evaluated for 6 months post-immunization. Immunogenicity for all serogroups was assessed for non-inferiority between MPV-4 and MCV-4 30 days post immunization by serum bactericidal antibody assay using baby rabbit complement (rSBA). From December 2020 to July 2021, 260 healthy subjects were consented and randomized. At Day 30 post-immunization, the proportions of subjects with rSBA titers ≥ 128 for all serogroups in the MPV-4 group were non-inferior to those in MCV-4 group. The proportions of subjects with rSBA ≥ 4-fold increase and rSBA titers ≥ 8 for all serogroups were similar among vaccine groups (P > .05). Geometric Mean Titers and Geometric Mean Fold Increases for all serogroups in both vaccine groups were similar (P > .05). Few local and systemic post-immunization reactions of similar severity and duration were observed within 7 days and were similar in both groups (P > .05). All resolved without sequelae. Unsolicited adverse events were similar in both groups regarding relationship to study vaccine, severity and duration. No serious adverse events were reported during the study period. MPV ACYW135 showed a non-inferior immunogenicity profile and a comparable reactogenicity profile to MCV-4 in Malian children aged 2–10 years. Clinical Trial Registration: NCT04450498.

Immunogenicity and safety of a quadrivalent meningococcal conjugate vaccine (MenACYW-TT) administered as a booster to adults aged ≥59 years: A phase III randomized study

ABSTRACT This 2-stage Phase III study (NCT04142242) of a recently licensed quadrivalent meningococcal tetanus toxoid-conjugate vaccine (MenACYW-TT) assessed the safety and immunogenicity of a booster dose in older adults (≥59 years) primed with either MenACYW-TT or a quadrivalent meningococcal polysaccharide vaccine (MPSV4). Immune persistence of MenACYW-TT and MPSV4 after primary vaccination was also evaluated. During Stage I, the participants administered MPSV4 (n = 165) or MenACYW-TT (n = 236) 3 years previously were randomized 9:2 to receive either a MenACYW-TT booster or to have blood drawn for persistence only. Participants primed with MPSV4 or MenACYW-TT 6–7 years previously had blood drawn for antibody persistence only. A serum bactericidal assay using human complement was used to measure functional antibodies against each serogroup at baseline and, for those receiving a booster, 30 days post-vaccination (D30). Proportions of participants with seroresponse (post-vaccination titers ≥1:16 when baseline titers <1:8 or ≥ 4-fold increase when baseline titers ≥1:8) were determined. Safety data were collected up to D30. Seroresponse rates for all serogroups at D30 ranged from 49.2% to 60.8% in the MPSV4-primed group, and 79.3–93.1% in the MenACYW-TT-primed group. MenACYW-TT induced sufficient seroresponses in each primed group. Geometric mean titers (GMTs) for serogroups C, W, and Y remained or trended higher than pre-vaccination levels at both 3 and 6–7 years after primary vaccination, indicating immune persistence. Safety outcomes were comparable between groups. A MenACYW-TT booster was immunogenic and well tolerated in participants aged ≥59 years regardless of previous quadrivalent meningococcal vaccine received. The greatest immune responses occurred in those primed with MenACYW-TT.

1046. Immunogenicity and Safety of a Quadrivalent Meningococcal Conjugate Vaccine (MenACYW-TT) Administered as a Booster to Adults ≥ 59 Years of Age

Abstract Background MenACYW-TT (MenQuadfi®, Sanofi) is a quadrivalent (serogroups A, C, W, and Y) meningococcal tetanus toxoid conjugate vaccine. It was recently approved for use in persons aged ≥ 2 years in the US and persons aged ≥ 1 year in Europe and certain other countries; trials in infants as young as 6 weeks are ongoing. This study evaluated seroresponse after a MenACYW-TT booster given to adults who received either quadrivalent meningococcal polysaccharide vaccine (MSPV4) or MenACYW-TT three years earlier at age ≥ 56 years. Immune persistence up to 7 years after primary vaccination was also evaluated. Methods This was a Phase 3 randomized, open-label study (NCT04142242) of adults aged ≥ 59 years who participated in previous studies of MenACYW-TT vs MPSV4 (NCT01732627 and NCT02842866). The study was conducted in the US and Puerto Rico. Immune response and persistence were assessed with a serum bactericidal assay using human complement (hSBA). Sufficiency of the vaccine seroresponse was considered demonstrated if the lower limit of the 1-sided 97.5% CI for the percentage of subjects with an hSBA vaccine seroresponse against serogroups A, C, W and Y was &amp;gt; 40%. Safety data were collected up to 30 days after booster vaccination. Results A total of 471 persons were enrolled. Sufficiency of a MenACYW-TT booster was demonstrated for MPSV4- and for MenACYW-TT-primed subjects. hSBA seroresponse rates were higher among MenACYW-TT- vs MPSV4-primed subjects (79.3%–93.1% vs 49.2%–60.8%, respectively). Three to 7 years after primary vaccination, hSBA geometric mean titers (GMTs) and seroprotection rates (SPRs) declined in both MenACYW-TT- and MPSV4-primed subjects, with hSBA GMTs and SPRs for serogroups C, W, and Y generally remaining higher for MenACYW-TT- vs MPSV4-primed subjects; those for serogroup A were similar regardless of priming vaccine. Rates of adverse events following a MenACYW-TT booster were similar between MenACYW-TT- and MPSV4-primed subjects. No safety concerns were identified. Conclusion A MenACYW-TT booster was well tolerated and immunogenic when administered to either MPSV4- or MenACYW-primed adults aged ≥ 59 years. Up to 7 years after primary vaccination, immune persistence for serogroups C, W, and Y tended to be greater for MenACYW-TT vs MPSV4. Disclosures Corwin A. Robertson, MD, MPH, FACP, Sanofi Pasteur (Employee, Other Financial or Material Support, Stockholder) Alexandre Selmani, PhD, Sanofi Pasteur (Employee) Katherine Galarza, MD, Sanofi Pasteur (Employee) Philipp Oster, MD, Sanofi Pasteur (Employee, Stockholder)

Ten-Year Antibody Persistence and Booster Response to MenACWY-TT Vaccine After Primary Vaccination at 1-10 Years of Age

ABSTRACT This phase 3B, open-label, extension study (NCT01962207) evaluated long-term persistence of antibodies induced by the quadrivalent meningococcal vaccine conjugated to tetanus toxoid (MenACWY-TT) compared with the meningococcal serogroup C vaccine conjugated to CRM (MenC-CRM) and the quadrivalent meningococcal polysaccharide vaccine (MenACWY-PS) 6 to 10 y after primary vaccination in toddlers (aged 1–<2 y; MenACWY-TT and MenC-CRM) and children (aged 2–<11 y; MenACWY-TT and MenACWY-PS). Antibody responses against meningococcal serogroups A, C, W, and Y were assessed by serum bactericidal antibody assays using rabbit (rSBA) or human (hSBA) complement. A MenACWY-TT booster dose at Year 10 was given to all eligible subjects regardless of the primary vaccine received. At Year 10, the percentages of subjects with rSBA titers ≥1:8 for serogroups A, C, W, and Y were as follows: MenACWY-TT (toddlers), 65.6%, 82.8%, 31.3%, 43.8%, respectively; MenC-CRM, 88.2% for serogroup C; MenACWY-TT (children), 88.9%, 84.1%, 67.1%, 65.9%; and MenACWY-PS, 28.6%, 81.0%, 23.8%, and 23.8%. Corresponding percentages for hSBA titers ≥1:4 were as follows: MenACWY-TT (toddlers), 31.1%, 91.9%, 44.4%, 41.4%; MenC-CRM, 93.8% for serogroup C; MenACWY-TT (children), 34.8%, 91.1%, 61.2%, 72.6%; and MenACWY-PS, 33.3%, 100.0%, 26.3%, and 44.4%. One month after the MenACWY-TT booster, the percentage of subjects with vaccine response ranged from 75.7% to 100.0% across serogroups in all study groups. Postbooster vaccine responses were generally comparable between groups across serogroups. No new safety signals were identified. Antibody responses persisted 10 y after MenACWY-TT vaccination. The MenACWY-TT booster dose was well tolerated and elicited robust immune responses.

Efficacy and safety of a booster dose of the meningococcal A, C, W, Y-tetanus toxoid conjugate vaccine administered 10 years after primary vaccination and long-term persistence of tetanus toxoid conjugate or polysaccharide vaccine

ABSTRACT A previous phase 3, randomized, multicenter study showed the immunogenicity of a primary vaccination of subjects aged 11 to 17 years with the quadrivalent meningococcal vaccine conjugated to tetanus toxoid (MenACWY-TT) or the quadrivalent meningococcal polysaccharide vaccine (MenACWY-PS). This extension study evaluated the safety and immunogenicity of a MenACWY-TT booster 10 years after receiving a primary dose of either MenACWY-TT or MenACWY-PS. The primary immunogenicity endpoint was booster response, evaluated using serum bactericidal antibody assays with rabbit complement (rSBA), 1 month postbooster. Safety endpoints included the percentage of subjects experiencing local and general adverse events (AEs) ≤4 days after MenACWY-TT booster. Of 229 subjects enrolled, 169 and 58 in the MenACWY-TT and MenACWY-PS groups, respectively, completed the booster phase. The 1 month postbooster response for each serogroup ranged from 81.5% to 95.7% for MenACWY-TT and 66.7% to 94.1% for MenACWY-PS. Similar percentages of MenACWY-TT and MenACWY-PS recipients had a booster response to serogroups A, W, and Y, whereas more MenACWY-TT recipients than MenACWY-PS recipients had a booster response to serogroup C. For the MenACWY-TT and MenACWY-PS groups, respectively, the MenACWY-TT booster elicited rSBA titers ≥1:8 in 100% and ≥98.0% of subjects across all serogroups; 100% and ≥96.1% of all subjects had titers ≥1:128. No new safety signals were observed during the booster phase. In conclusion, a MenACWY-TT booster dose after receiving either a primary dose of MenACWY-TT or MenACWY-PS elicited robust immune responses and was well tolerated. Functional antibody responses last up to 10 years after primary MenACWY-TT vaccination.

Immunogenicity and safety of a quadrivalent meningococcal tetanus toxoid-conjugate vaccine (MenACYW-TT) in adults 56 years of age and older: a Phase II randomized study

ABSTRACT MenACYW-TT is an investigational quadrivalent meningococcal conjugate vaccine intended for the prevention of invasive meningococcal disease (IMD) caused by serogroups A, C, W, and Y in individuals aged 6 weeks and above. This Phase II, randomized, open-label, multicenter, exploratory study assessed the safety and immunogenicity of MenACYW-TT compared with a quadrivalent meningococcal polysaccharide vaccine (MPSV4) in 301 healthy adults aged ≥56 y in the US (NCT01732627). Participants were randomized 2:1 to receive MenACYW-TT or MPSV4. Serum bactericidal assays using human (hSBA) or baby rabbit (rSBA) complement were used to measure functional antibodies against meningococcal serogroups A, C, W, and Y at baseline and 30 d post-vaccination. Safety data were collected up to 30 d post-vaccination. Proportions of study participants with hSBA titers ≥1:8 against serogroups A, C, W, and Y were increased at Day 30 compared with baseline in both vaccine groups. The proportions of participants with hSBA titers ≥1:8 after MenACYW-TT vaccination were comparable to those after MPSV4 vaccination for serogroups A and C (A: 93.8% vs. 85.1%; C: 74.9% vs. 62.8%) and distinctly higher than after MPSV4 for serogroups W and Y (W: 79.5% vs. 60.6%; Y: 80.5% vs. 59.6%). Proportions of participants with rSBA titers ≥1:8 were comparable between vaccine groups for all four serogroups. The reactogenicity profiles of both vaccines were similar. Most unsolicited adverse events (AEs) were of Grade 1 or Grade 2 intensity, and no serious AEs were reported. The MenACYW-TT conjugate vaccine was well tolerated and immunogenic in adults aged ≥56 y.

2462. Immunogenicity and Safety of a Quadrivalent Meningococcal Conjugate Vaccine (MenACYW-TT) Administered in Individuals 56 Years of Age and Older

BackgroundThe MenACYW-TT conjugate vaccine is a quadrivalent meningococcal vaccine candidate intended for global use in all age groups. This Phase III study evaluated the safety and immunogenicity of the vaccine when compared with a licensed quadrivalent meningococcal polysaccharide vaccine (MPSV4) in adults ≥56 years of age.MethodsA randomized, modified double-blind, multicenter study (NCT02842866) was conducted in 907 healthy adults in the United States. Participants were randomized to receive a single dose of either MenACYW-TT conjugate vaccine or MPSV4, stratified according to age into 2 subsets: 56 to 64 and ≥65 years. Descriptive analyses were also planned for age subsets 65–74 years and ≥75 years. Serum bactericidal assay with human (hSBA) and baby rabbit (rSBA) complement was used to measure antibodies against serogroups A, C, Y, and W test strains at baseline and 30 days after vaccination. Safety data were collected up to six months post-vaccination.ResultsNon-inferiority of immune responses was demonstrated between MenACYW-TT conjugate vaccine and MPSV4 based on percentages of subjects achieving hSBA vaccine seroresponse for serogroups A, C, Y, and W at Day 30 compared with baseline. The proportions of individuals with hSBA ≥ 1:8 obtained after MenACYW-TT conjugate vaccine were higher than those after MPSV4 for all four serogroups (A: 89.4% vs. 84.2%; C: 90.1% vs. 70.9%; W: 77.4% vs. 63.0%; Y: 91.7% vs. 67.7%). Overall, the results were similar in the three age substrata. Percentages of participants with post vaccination rSBA ≥ 1:128 were numerically higher for all serogroups in subjects vaccinated with MenACYW-TT conjugate vaccine. A difference in the local reactogenicity profiles was observed between the two vaccine groups, possibly influenced by the different routes of administration. Most unsolicited adverse events were of Grade 1 or Grade 2 intensity. No vaccine related serious adverse events were reported.ConclusionMenACYW conjugate vaccine was immunogenic and well tolerated when administered to individuals ≥56 years of age. Such a vaccine will offer an alternative for the prevention of invasive meningococcal disease in areas of the world where only polysaccharide vaccines are currently available for immunization of older adults.Disclosures A. Esteves-Jaramillo, Sanofi Pasteur: Employee, Educational support and Salary. D. Neveu, Sanofi Pasteur: Employee, Salary. M. S. Dhingra, Sanofi Pasteur: Employee, Educational support and Salary.

Trends and variations in the epidemiology of meningococcal disease in Kuwait 1987-2013.

The introduction of Haemophilus influenzae type b (Hib) conjugate vaccine and conjugate pneumococcal vaccine into routine childhood vaccination in Kuwait has resulted in the emergence of Neisseria meningitidis as the leading cause of invasive bacterial infection in children. Currently, a quadrivalent ACYW-135 meningococcal polysaccharide vaccine is administered as part of routine childhood vaccination in Kuwait at the age of 2 years. Conjugate meningococcal vaccines have been shown to be more effective in preventing meningococcal infection in young children. The objective of this study was to describe the epidemiology of meningococcal disease (MD) in Kuwait and evaluate the need for conjugate vaccine in routine childhood immunization. We have reviewed the MD surveillance data from the communicable disease unit, Ministry of Health, Kuwait during the period from 1987 to 2013. The analysis included microbiologically confirmed cases of N. meningitidis in the blood and cerebrospinal fluid. There were 293 cases of confirmed MD during the study period. Two hundred and four cases (70%) were in children ≤ 14 years of age. The mean incidence rate was 0.5/100,000 persons. The dominant serogroups were W-135 and B, accounting for 80 cases (32%) each. Serogroup B accounted for 69/204 (34%) of all cases in children ≤ 14 years and serogroup A accounted for 36/89 40% of all adult cases. There were three outbreaks: 1987 (caused by serogroup A), 1989 (caused by serogroup W-135) and 2002 (caused by serogroup B). The mean case fatality rate was 13.5%. In conclusion, despite childhood routine vaccination with ACYW-135 polysaccharide vaccine, infants and young children remain at high risk for MD, which supports the introduction of conjugate meningococcal vaccine to the routine childhood vaccination schedule.

Meningococcal serogroup C serum and salivary antibody responses to meningococcal quadrivalent conjugate vaccine in Saudi Arabian adolescents previously vaccinated with bivalent and quadrivalent meningococcal polysaccharide vaccine

Following repeated polysaccharide vaccination, reduced immune responses have been reported, but there are limited data on the mucosal response of meningococcal polysaccharide vaccine (PSV) or meningococcal conjugate vaccination. Saudi Arabian adolescents (aged 16–19 years) who had previously been vaccinated with ≥1 dose of bivalent meningococcal polysaccharide vaccine and 1 dose of quadrivalent meningococcal polysaccharide (MPSV4) were enrolled in a controlled, randomised, and modified observer-blind study (collectively termed the PSV-exposed group). The PSV-exposed group was randomised to receive either quadrivalent meningococcal conjugate vaccine (MCV4) (PSV-exposed/MCV4 group) or MPSV4 (PSV-exposed/MPSV4 group), and a PSV-naïve group received MCV4. Serum and saliva samples were collected pre-vaccination and 28 days post-vaccination. Serum serogroup-specific A, C, W and Y IgG were quantified as were salivary serogroup-specific C IgG and IgA together with total salivary IgG and IgA. For each serogroup, the post-vaccination serum geometric mean concentrations (GMCs) were significantly higher in the PSV-naïve and the PSV-exposed/MCV4 group than in the PSV-exposed/PSV4 group. For serogroup C, serum serogroup-specific IgG for the PSV-naïve group was significantly higher than both the PSV exposed groups. Higher levels of salivary serogroup C-specific IgG were found in the PSV-naïve group than those who had received two doses of polysaccharide but no significant differences were noted with regards to serogroup-specific IgA.

Persistence of antibodies in laboratory staff immunized with quadrivalent meningococcal polysaccharide vaccine

BackgroundOccupational exposure to live meningococci can potentially cause invasive meningococcal disease in laboratory staff. While, until recently, immunization with quadrivalent polysaccharide vaccine represented one cornerstone of protection, data on long-term persistence of antibodies in adults remain scarce.MethodsWe analyzed the relationship of antibody levels and time following quadrivalent polysaccharide vaccination (Mencevax® ACWY, GlaxoSmithKline) in a cross-sectional sample of 20 laboratory workers vaccinated at ages between 16.4 to 40.7 years from Germany. Sera were obtained 0.4 to 158.5 (median 35.3) months after vaccination. At the time of sampling, laboratory workers had been regularly exposed to meningococci for periods between 3.2 to 163.8 (median 41.2) months. Serum bactericidal assay (SBA) with rabbit complement and a microsphere-based flow analysis method were used to determine bactericidal titers and concentrations of IgG, respectively, against serogroups A, C, W135, and Y. Decay of antibodies was modeled using linear regression. Protective levels were defined as SBA titers ≥ 8.ResultsHalf-lives of SBA titers against serogroups A, C, W135, and Y were estimated at 27.4, 21.9, 18.8, and 28.0 months, respectively. Average durations of protection were estimated at 183.9, 182.0, 114.6, and 216.4 months, respectively. Inter-individual variation was high; using lower margins of 95% prediction intervals, minimal durations of protection against serogroups A, C, W135 and Y were estimated at 33.5, 24.6, 0.0, and 55.1 months, respectively. The proportion of staff with protective SBA titers against W135 (65.0%) was significantly lower than proportions protected against A (95.0%), C (94.7%), and Y (95.0%). Consistently, geometric mean titer (97.0) and geometric mean concentration of IgG (2.1 μg/ml) was lowest against serogroup W135. SBA titers in a subset of individuals with incomplete protection rose to ≥ 128 (≥ 8 fold) after reimmunization with a quadrivalent glycoconjugate vaccine.ConclusionsThe average duration of protection following immunization with a quadrivalent polysaccharide vaccine in adults was ≥ 115 months regardless of serogroup. A substantial proportion (approximately 23% according to our decay model) of adult vaccinees may not retain protection against serogroup W135 for five years, the time suggested for reimmunization.

Acquisition of Meningococcal Serogroup W-135 Carriage in Turkish Hajj Pilgrims Who Had Received the Quadrivalent Meningococcal Polysaccharide Vaccine

Invasive meningococcal disease is a recognized public health problem worldwide, with a dynamic and changeable epidemiology. In Turkey, the second most common pathogenic meningococcal serogroup (after serogroup B) is W-135, including an epidemic in 2005, which has been strongly associated with Hajj pilgrims and their close contacts. In two studies conducted in 2010, we assessed meningococcal carriage in intending Turkish pilgrims to the Hajj when they attended to receive a plain polysaccharide vaccine against serogroups A, C, W-135, and Y and, upon their return, to determine the acquisition of meningococcal carriage by the pilgrims themselves and subsequently their household contacts. Nasopharyngeal swabs were obtained from pilgrims before the Hajj and upon their return. Swabs were then obtained from 39 household contacts of pilgrims who were shown to have acquired carriage during the Hajj. Of the 472 pilgrims before the Hajj, 63 (13%) were positive for meningococcal carriage, of which 52 cases (83%) were serogroup W-135. In the 296 pilgrims tested after the Hajj, 81 (27%) were positive for meningococcal carriage, including 74 (91%) with W-135. In 11 family members of pilgrims who acquired W-135 carriage at the Hajj, 10 (91%) had acquired carriage of serogroup W-135. This study illustrates the acquisition of meningococcal carriage, predominantly of serogroup W-135 by pilgrims attending the Hajj, and the transmission of this carriage to their family members on their return, explaining the source of W-135 meningococcal disease in Turkey.

Immunogenicity and safety of a new meningococcal A conjugate vaccine in Indian children aged 2–10 years: A Phase II/III double-blind randomized controlled trial

This study compares the immunogenicity and safety of a single dose of a new meningococcal A conjugate vaccine (PsA-TT, MenAfriVac™, Serum Institute of India Ltd., Pune) against the meningococcal group A component of a licensed quadrivalent meningococcal polysaccharide vaccine (PsACWY, Mencevax ACWY®, GSK, Belgium) 28 days after vaccination in Indian children. This double-blind, randomized, controlled study included 340 Indian children aged 2–10 years enrolled from August to October 2007; 169 children received a dose of PsA-TT while 171 children received a dose of PsACWY. Intention-to-treat analysis showed that 95.2% of children in PsA-TT group had a ≥4-fold response in serum bactericidal titers (rSBA) 28 days post vaccination as compared to 78.2% in the PsACWY group. A significantly higher rSBA GMT (11,209, 95%CI 9708–12,942) was noted in the PsA-TT group when compared to PsACWY group (2838, 95%CI 2368–3401). Almost all children in both vaccine groups had a ≥4-fold response in group A-specific IgG concentration but the IgG GMC was significantly greater in the PsA-TT group (89.1μg/ml, 95%CI 75.5–105.0) when compared to the PsACWY group (15.3μg/ml, 95%CI 12.3–19.2). Local and systemic reactions during the 4 days after immunization were similar for both vaccine groups except for tenderness (30.2% in PsA-TT group vs 12.3% in PsACWY group). None of the adverse events or serious adverse events was related to the study vaccines. We conclude that MenAfriVac™ is well tolerated and significantly more immunogenic when compared to a licensed polysaccharide vaccine, in 2-to-10-year-old Indian children.

Recommended Adult Immunization Schedule: United States, 2012*

Recommended Adult Immunization Schedule: United States, 2012*

Early clinical experience with a candidate meningococcal B recombinant vaccine (rMenB) in healthy adults

Background: The development of a broadly protective vaccine against meningococcal serogroup B is a well-recognized public health need. Whole-genome sequencing was used to identify meningococcal surface proteins that are conserved across strains. These proteins were incorporated into two investigational vaccines.Methods: Three randomized studies were performed to evaluate a three-component recombinant meningococcal serogroup B vaccine (rMenB) and rMenB plus outer membrane vesicles from the Norwegian outbreak strain 44/76 (rMenB+OMVNW). Participants were randomized to receive 3 or 4 doses of rMenB or rMenB+OMVNW or control vaccines and provided sera for exploratory immunogenicity testing against a panel of meningococcal serogroup B strains. A booster dose was administered 12 months after the initial primary series in one of the studies. The control cohort received a licensed quadrivalent meningococcal polysaccharide vaccine against serogroups A, C, W-135 and Y as well as hepatitis B vaccine as safety comparators. Solicited reactions within 7 days of any vaccination and adverse events throughout the studies were recorded.Results: One hundred four participants enrolled into the clinical trials. Both rMenB and rMenB+OMVNW induced immune responses to multiple serogroup B strains in the majority of participants. Compared with rMenB, rMenB+OMVNW appeared somewhat more immunogenic and reactogenic; the study was not adequately powered for statistical assessment of these small differences. Both investigational vaccines were more reactogenic than the licensed vaccines. Few vaccinees discontinued any study due to reactogenicity to any study vaccine administered.Conclusion: Based on the immunogenicity and reactogenicity results in these participants, both rMenB and rMenB+OMVNW were promising candidates for further investigation.

Neisseria meningitidis Serogroup X Sequence Type 767 in Turkey

Neisseria meningitidis is a common inhabitant of the nasopharyngeal tracts of healthy humans and is a significant cause of invasive infections such as meningitis in young children and adolescents worldwide (14). N. meningitidis has been classified into 13 serogroups on the basis of antigenic variation of the capsule, but only serogroups A, B, C, Y, and W-135 have commonly caused invasive infections (8). In Turkey, W-135 has been the most frequently reported serogroup since an international outbreak was reported following the annual Hajj seasons in Saudi Arabia in 2000 and 2001 (10). During the years 2003 to 2008, 17 serogroup W-135 strains (from eight meningitis cases) were isolated from Turkish recruits vaccinated with A+C polysaccharide meningococcal vaccine (10-12). We describe here the first meningococcal meningitis case caused by a serogroup X N. meningitidis strain in Turkey. The patient was a 22-year-old male soldier, working in a military unit, who was admitted to the emergency department with complaints of a 1-week history of fever (39°C), cough, and vomiting on 10 January 2010. There was little petechiate rash on his chest and a lower leg. The laboratory evaluation at that time revealed a leukocyte count of 3,700/mm3, a hemoglobin level of 13.4 g/dl, and an erythrocyte sedimentation rate of 5 mm/h. The patient was then admitted to the infectious disease service with a diagnosis of meningococcal meningitis based on the clinical symptoms and results of confirmatory laboratory tests, including blood culture and cerebrospinal fluid analysis. He was given ceftriaxone (4 g/day) for 10 days and then discharged from the hospital in good condition. Oropharyngeal swab specimens were obtained from the patient's close military personnel contacts, and one person was found to be positive for an N. meningitidis serogroup X strain. He was given a single dose of 500 mg ciprofloxacin immediately. Clinical and oropharyngeal swab specimens were inoculated immediately onto BBL-modified Thayer-Martin medium plates (MTM II; Becton Dickinson Microbiology Systems) and Thayer-Martin medium with VCAT selective supplement (SR10B; Oxoid, Hampshire, England). After incubation, suspect colonies were identified by Gram staining and oxidase reactivity testing and the identification was confirmed by the API NH system (bioMerieux) (4). An antibiotic susceptibility test was performed by the Etest method (AB BIODISK, Solna, Sweden) for ciprofloxacin, ceftriaxone, cefotaxime, penicillin, rifampin, and chloramphenicol (3). The strains were susceptible to the antibiotics tested, except penicillin, with a MIC of 0.75 μg/ml. Serogrouping of the meningococcal isolates was performed by a slide agglutination technique as recommended by Difco Laboratories (Detroit, MI). porA variant region sequencing was performed using the standard primers and identified by querying the respective databases hosted at http://neisseria.org. Multilocus sequence typing (MLST) was performed using the standard primers listed at the Neisseria MLST website (http://pubmlst.org/neisseria/). The isolates had the strain designation X: P1.5-1,10-1: sequence type 767 (ST-767) (cc167). ST-767 meningococci have been found previously among N. meningitidis serogroup A and Y strains in Europe and Africa between 1999 and 2008 (http://pubmlst.org/neisseria/). PFGE typing of NheI-digested DNA was performed by a modification of a previously described method (12). The clinical and carrier isolates had the same genotypic pattern. N. meningitidis serogroup X strains were first described in the 1960s and have been isolated from a few cases of invasive meningococcal diseases in North America, Europe, Australia, and China (2, 6, 7). Outbreaks of N. meningitidis serogroup X strains have been reported in Niger (1), western Kenya (13), and northern Ghana (5). N. meningitidis serogroup X strains were reported to be very efficient in colonization among military recruits in the United Kingdom (9). Before May 2009, eight invasive meningococcal disease cases caused by serogroup W-135 were reported in Turkish soldiers who had been vaccinated with A+C polysaccharide meningococcal vaccine; four of these were fatal. Since that time, a quadrivalent meningococcal polysaccharide vaccine (against A/C/Y/W-135) has been successfully introduced into the Turkish recruit expanded immunization program. We describe here the first meningococcal meningitis case caused by a serogroup X strain in our recruits since the introduction of the quadrivalent vaccine. It was reported that repeated mass vaccination in many African countries might have contributed to colonization by and meningococcal diseases due to serogroup X strains and might result in a changed profile of meningococcal disease (5). We suggest that comprehensive conjugate vaccines including X polysaccharides should be developed. In addition, these data highlight the need for further epidemiological surveillance to carefully monitor the pattern of incidence of meningococcal diseases caused by serogroup X strains and to inform future public health strategies.

Immunogenicity and tolerability of a quadrivalent meningococcal glycoconjugate vaccine in children 2–10 years of age

Meningococcal disease incidence is highest in infants, but a significant burden of disease also occurs in children. In this Phase II, single-centre US study, 619 healthy children (2–10 years of age) received one dose of an investigational quadrivalent meningococcal CRM 197-conjugated vaccine (MenACWY-CRM) or a licensed quadrivalent meningococcal polysaccharide vaccine (MPSV4). Immunogenicity was assessed using the serum bactericidal assay with human complement (hSBA) at 1 and 12 months post-vaccination. Local and systemic reactions were recorded for 7 days, all adverse events (AEs) for 1 month, and medically significant and serious AEs (SAEs) for 12 months post-vaccination. For all four serogroups, more MenACWY-CRM recipients achieved an hSBA titre ≥1:4 at 1 month post-vaccination (A: 82%; C: 83%; W-135: 95%; Y: 91%) compared with the group that received MPSV4 (A: 45%; C: 66%; W-135: 71%; Y: 61%); this difference persisted through to 12 months post-vaccination. Both vaccines were well tolerated. In children 2–10 years of age, MenACWY-CRM induced a higher immune response than that of MPSV4, and was well tolerated.

The new meningococcal conjugate vaccine

PREVIEWMeningococcal disease is a serious illness affecting all age-groups. Infants under 1 year of age, adolescents, and young adults are also especially susceptible. An effective quadrivalent meningococcal plain polysaccharide vaccine has been available for decades. However, inherent limitations of plain polysaccharide vaccines include limited duration of immunity, the potential for hyoporesponsiveness with repeated vaccinations, and ineffectiveness in children under age 2 years. The recently developed and licensed quadrivalent meningococcal conjugate vaccine should prove to provide important advantages over the plain polysaccharide vaccine. In this article, Dr Pichichero discusses these advantages, current recommendations for administration, and prospects for broader vaccine coverage.

Comparative Trial of the Safety and Immunogenicity of Quadrivalent (A, C, Y, W-135) Meningococcal Polysaccharide-Diphtheria Conjugate Vaccine Versus Quadrivalent Polysaccharide Vaccine in Two- to Ten-Year-Old Children

A quadrivalent meningococcal diphtheria conjugate vaccine (MCV-4) has been developed to provide T-cell dependent immune responses against 4 major disease-causing serogroups (A, C, Y, W-135). In a comparative, randomized, modified double blind, controlled study in healthy 2- to 10-year-old U.S. children, safety and immunogenicity profiles of MCV-4 (n = 696) were compared with those of a licensed quadrivalent polysaccharide vaccine, Menomune A/C/Y/W-135 (PSV-4, n = 702). Vaccine-related adverse reactions were assessed for 28-day and 6-month follow-up periods. Serum bactericidal activity (SBA) was assayed in prevaccination, day 28 and 6-month postvaccination sera samples. Both vaccines were well-tolerated, with no vaccine-related serious adverse events and similar rates of mostly mild local and systemic reactions. Functional antibody (SBA) seroconversion percentages were significantly higher for all 4 serogroups in the MCV-4 group. The SBA geometric mean titers against serogroups A, C, Y and W-135 with MCV-4 were 1700, 354, 637 and 750, respectively, compared with PSV-4 (893, 231, 408 and 426) 28 days postvaccination (P < 0.001 for all comparisons). This significant difference persisted through 6 months. In 2- to 10-year-old children MCV-4 had a safety profile similar to that of PSV-4 and elicited significantly higher and more persistent serum bactericidal antibody responses against meningococcal serogroups A, C, Y and W-135 than did the licensed polysaccharide vaccine.

Anticapsular polysaccharide meningococcal antibodies in Israeli military recruits: immune status and the effect of simultaneous administration of immune globulin on the response to polysaccharide vaccine

The effect of the administration of immune globulin (Ig), given during summer months to prevent hepatitis A, on the immune response to a simultaneously administered quadrivalent meningococcal polysaccharide vaccine (QMPV) was studied in Israeli military recruits. Data were obtained for the first time regarding the immune status of an Israeli population. Anticapsular polysaccharide antibodies were determined using a standardized ELISA assay before, 2 weeks and 3 months after QMPV immunization with or without Ig in two groups of recruits chosen to span the date determining seasonal administration or non-administration of Ig. Pre-vaccination antibody concentrations were ≥2 μg/ml in 98.4 and 38.9% of subjects against serogroups A and C meningococci, respectively. These levels are consistent with the extremely low incidence of disease due to serogroup A in Israel, and with the previously documented occurrence of serogroup C disease in servicemen and women. Co-administration of Ig was associated with some reduction in antibody concentrations 3 months after vaccination, especially against serogroup A meningococci ( P<0.05), but not to an extent likely to be of clinical significance.