Prevalence of Serum Bactericidal Antibody to Serogroup C Neisseria meningitidis in England a Decade after Vaccine Introduction

ABSTRACTSerogroup C meningococcal disease incidence and carriage declined rapidly in the United Kingdom after infant serogroup C conjugate vaccination was introduced in 1999, with catch-up vaccination for children under 18 years. Antibody levels and effectiveness waned quickly in children vaccinated at 2, 3, and 4 months of age. Therefore, in 2006, the current revised schedule of doses at 3, 4, and 12 months was introduced. This study assessed age-specific protection in 2009 compared with data from historical prevaccination and early postvaccination studies. Rabbit complement serum bactericidal antibody (SBA) was measured in anonymously banked serum samples collected in England in 2009 (n= 1,174), taking titers of ≥8 as protective. Age-stratified proportions of SBA titers that were ≥8 and geometric mean titers were compared. SBA titers varied markedly by birth cohort and time since vaccination. Overall, 35% of samples (95% confidence interval [CI], 33 to 38%) had titers that were ≥8. Only in cohorts eligible for catch-up vaccination did the majority of individuals have protective antibody levels. Antibody levels were higher in children eligible for vaccination at primary and secondary school ages, compared to those eligible below the age of 5 years. In those eligible for completed vaccination under the current schedule, protective levels were very modest and there was no evidence of superiority to cohorts that were eligible for the previous schedule. This supports a need for older childhood or adolescent booster vaccination in those previously eligible for vaccination during the infant, toddler, or preschool periods, to maintain direct protection and potentially enhance population immunity.

Download Full-text

Seroprevalence of Antibodies against Serogroup C Meningococci in England in the Postvaccination Era

Clinical and Vaccine Immunology ◽

10.1128/cvi.00279-08 ◽

2008 ◽

Vol 15 (11) ◽

pp. 1694-1698 ◽

Cited By ~ 57

Author(s):

Caroline L. Trotter ◽

Ray Borrow ◽

Jamie Findlow ◽

Ann Holland ◽

Sarah Frankland ◽

...

Keyword(s):

Similar Pattern ◽

Geometric Mean ◽

Herd Immunity ◽

Age Groups ◽

Serum Samples ◽

The United Kingdom ◽

Specific Igg ◽

Catch Up ◽

Antibody Levels ◽

Mean Concentration

ABSTRACT The United Kingdom introduced meningococcal serogroup C conjugate (MCC) vaccines in 1999, resulting in substantial declines in serogroup C disease and carriage. Here, we measured the age-specific prevalence of serum bactericidal antibodies (SBA) to Neisseria meningitidis serogroup C and immunoglobulin G (IgG) concentrations to serogroups A, C, W-135, and Y in 2,673 serum samples collected in England between 2000 and 2004. We compared the seroprevalence of SBA titers of ≥8 in the postvaccination era with results from an earlier prevaccination study conducted using the same methods. We found that the percentages of individuals with protective SBA titers were higher in 2000 to 2004 in all of the age groups targeted for MCC vaccination. In the postvaccine era, the prevalence of protective titers was high (75%) in children who had recently been offered routine immunization, but this fell to 36% more than 18 months after scheduled immunization. In the cohorts targeted in the catch-up campaign, the percentage achieving SBA titers of ≥8 was higher in children offered the vaccine at ages 5 to 17 years than in children offered the vaccine at ages 1 to 4 years. The geometric mean concentration (GMC) IgG for serogroup C followed a similar pattern, corresponding to the age at and time since scheduled MCC vaccination. Serogroup-specific IgG GMCs for W-135 and Y were low and showed little variation by age. Serogroup A IgG GMCs were higher, possibly reflecting exposure to cross-reacting antigens. Although the incidence of serogroup C disease remains low due to persisting herd effects, population antibody levels to serogroup C meningococci should be monitored so that potentially susceptible age groups can be identified should herd immunity wane.

Download Full-text

Maintenance of Immune Response throughout Childhood following Serogroup C Meningococcal Conjugate Vaccination in Early Childhood

Clinical and Vaccine Immunology ◽

10.1128/cvi.05354-11 ◽

2011 ◽

Vol 18 (12) ◽

pp. 2038-2042 ◽

Cited By ~ 22

Author(s):

A. Khatami ◽

A. Peters ◽

H. Robinson ◽

N. Williams ◽

A. Thompson ◽

...

Keyword(s):

Early Childhood ◽

Longitudinal Study ◽

Geometric Mean ◽

Booster Vaccination ◽

Nasopharyngeal Colonization ◽

Bactericidal Antibody ◽

Antibody Decline ◽

Conjugate Vaccination ◽

Kinetics Of ◽

Rabbit Complement

ABSTRACTThe objectives of this study were to evaluate the kinetics of antibody decline through childhood in a longitudinal study of a single cohort following serogroup C meningococcal (MenC) vaccine immunization in early childhood and to calculate the proportion of 11 to 13 year olds with protective levels of bactericidal antibody 10 years after immunization. United Kingdom children aged 11 to 13 years in 2010 who had previously taken part in a longitudinal study at the Oxford Vaccine Group had blood samples drawn between 2001 and 2010. Sera from each time point were analyzed for the MenC serum bactericidal antibody titer using a baby rabbit complement (rSBA) assay. The median age at MenC immunization was 21 months (range, 1 year 3 months to 3 years 9 months). The MenC rSBA geometric mean titer (GMT) at age 3.5 to 5 years was 8.0 (95% confidence interval, 6.5 to 9.9;n= 287). By age 11.5 to 13.5 years, the rSBA GMT had declined to 3.3 (2.5 to 4.4;n= 98). The percentage of children with rSBA titers of ≥1:8 (the threshold for protection) also declined from 38% (35% to 41%) to 15% (12% to 19%). We concluded that MenC rSBA titers wane rapidly following vaccination in early childhood and continue to decline into the second decade of life. Since nasopharyngeal colonization in adolescents probably provides the major reservoir for MenC in the population, declining immunity in this cohort is of concern. Sustaining high levels of antibody through booster vaccination in this cohort is likely necessary to avoid a resurgence of disease in the decade ahead.

Download Full-text

Serological Immunity to Smallpox in New South Wales, Australia

Viruses ◽

10.3390/v12050554 ◽

2020 ◽

Vol 12 (5) ◽

pp. 554

Author(s):

Valentina Costantino ◽

Mallory J. Trent ◽

John S. Sullivan ◽

Mohana P. Kunasekaran ◽

Richard Gray ◽

...

Keyword(s):

Vaccinia Virus ◽

New South ◽

Geometric Mean ◽

New South Wales ◽

Cell Mediated Immunity ◽

Preparedness Planning ◽

Population Immunity ◽

South Wales ◽

Primary Object ◽

Antibody Levels

The re-emergence of smallpox is an increasing and legitimate concern due to advances in synthetic biology. Vaccination programs against smallpox using the vaccinia virus vaccine ceased with the eradication of smallpox and, unlike many other countries, Australia did not use mass vaccinations. However, vaccinated migrants contribute to population immunity. Testing for vaccinia antibodies is not routinely performed in Australia, and few opportunities exist to estimate the level of residual population immunity against smallpox. Serological data on population immunity in Australia could inform management plans against a smallpox outbreak. Vaccinia antibodies were measured in 2003 in regular plasmapheresis donors at the Australian Red Cross Blood Service from New South Wales (NSW). The data were analysed to estimate the proportion of Australians in NSW with detectable serological immunity to vaccinia. The primary object of this study was to measure neutralising antibody titres against vaccinia virus. Titre levels in donor samples were determined by plaque reduction assay. To estimate current levels of immunity to smallpox infection, the decline in geometric mean titres (GMT) over time was projected using two values for the antibody levels estimated on the basis of different times since vaccination. The results of this study suggest that there is minimal residual immunity to the vaccinia virus in the Australian population. Although humoral immunity is protective against orthopoxvirus infections, cell-mediated immunity and immunological memory likely also play roles, which are not quantified by antibody levels. These data provide an immunological snapshot of the NSW population, which could inform emergency preparedness planning and outbreak control, especially concerning the stockpiling of vaccinia vaccine.

Download Full-text

Effects of Prior Polysaccharide Vaccination on Magnitude, Duration, and Quality of Immune Responses to and Safety Profile of a Meningococcal Serogroup C Tetanus Toxoid Conjugate Vaccination in Adults

Clinical and Diagnostic Laboratory Immunology ◽

10.1128/cdli.11.6.1100-1104.2004 ◽

2004 ◽

Vol 11 (6) ◽

pp. 1100-1104 ◽

Cited By ~ 36

Author(s):

Jo Southern ◽

Sarah Deane ◽

Lindsey Ashton ◽

Ray Borrow ◽

David Goldblatt ◽

...

Keyword(s):

Confidence Interval ◽

Immune Responses ◽

Geometric Mean ◽

Geometric Mean Titer ◽

Laboratory Staff ◽

Specific Immunoglobulin ◽

Bactericidal Antibody ◽

Conjugate Vaccination ◽

Time Point

ABSTRACT Extensive use of meningococcal AC polysaccharide (MACP) vaccines has raised concerns about induction of immunologic hyporesponsiveness to C polysaccharide. We investigated the immunogenicity and safety of a meningococcal C-tetanus conjugate (MCC-TT) vaccine in naïve adults and prior MACP vaccinees. Laboratory staff (n = 113) were recruited; 73 were naïve to meningococcal vaccination, and 40 had previously received ≥1 dose of MACP vaccine. Blood was taken prior to MCC-TT vaccination and 1 week, 1 month, and 6 months later. At each time point, proportions of subjects with serum bactericidal antibody (SBA) titers of ≥8 or ≥128 were similar (P > 0.46); >94% of subjects achieved titers of ≥128 at 1 month. However, the geometric mean titer (GMT) of SBA at 1 month was higher in the naïve (1,757; 95% confidence interval [95% CI], 1,102 to 2,803) than in the previously vaccinated (662; 95% CI, 363 to 1,207) group (P = 0.02), and similarly at 6 months (P < 0.001). Conversely, geometric mean concentrations (GMCs) of serogroup C-specific immunoglobulin G (IgG) were significantly higher in the previously vaccinated group pre-MCC-TT and at 1 week; the groups were similar at 1 month, and there was some evidence that the GMC for the previously vaccinated group was higher at 6 months. Qualitative differences in antibodies between groups were demonstrated by using the SBA/IgG ratio, though avidity measures were similar for the two groups throughout the study. MCC-TT was well tolerated, with similar safety profiles in the two groups. Pain in the arm and headache were the most frequently reported events following vaccination. The study shows that MCC-TT is safe and immunogenic in naïve and previously MACP-vaccinated adults, though the magnitude and persistence of postvaccination SBA responses in the latter group were lower.

Download Full-text

Vaccine waning and mumps re-emergence in the USA

Open Forum Infectious Diseases ◽

10.1093/ofid/ofx162.063 ◽

2017 ◽

Vol 4 (suppl_1) ◽

pp. S25-S25

Author(s):

Joseph Lewnard ◽

Yonatan H Grad

Keyword(s):

Vaccine Coverage ◽

Age Distribution ◽

Booster Vaccination ◽

Vaccine Effectiveness ◽

Vaccine Introduction ◽

Mumps Vaccine ◽

Population Immunity ◽

Clinical Protection ◽

The Usa ◽

History Of

Abstract Background Following decades of declining mumps incidence amid widespread vaccination, the US has experienced a resurgence in mumps cases since 2006 driven largely by outbreaks on college campuses. The occurrence of cases among previously-vaccinated individuals and in communities with high vaccine coverage has prompted concerns about performance of the live attenuated mumps vaccine (Jeryl Lynn strain) currently included in the measles-mumps-rubella (MMR) series. It is unclear whether the resurgence is due to antigenic changes in circulating mumps virus, which would warrant consideration of a new vaccine, or to waning vaccine-derived protection, necessitating additional booster doses. Methods We pooled data from studies of vaccine effectiveness to test for waning of protection. We used mathematical models to measure changes in population immunity since mumps vaccine introduction and to assess whether recent mumps transmission dynamics are consistent with hypotheses of waning immunity or vaccine escape. Results We estimate that vaccine-derived protection persists, on average, 29 (95% CI: 17–54) years after receipt of the last dose (Fig. 1). This waning accounts for 66.4% of unexplained variation in estimates of mumps vaccine effectiveness across published studies. Changes in age-specific susceptibility due to vaccine waning and declining transmission track with the current resurgence in cases among young adults in the USA, and explain outbreaks reported among vaccinated adolescents during the late 1980s (Fig. 2). In contrast, vaccine escape would not be expected to result in cases following the observed age distribution (Fig. 3). Routine adult booster vaccination is needed to sustain mumps elimination. Conclusion The resurgence of mumps in the USA since 2006 is attributable to waning of vaccine-derived immunity, suggesting the need for booster doses in adulthood. Trials are needed to assess clinical protection afforded by booster doses in individuals with a history of MMR vaccination. Disclosures J. Lewnard, Pfier: Grant Investigator, Research grant

Download Full-text

Evaluation of De-O-Acetylated Meningococcal C Polysaccharide-Tetanus Toxoid Conjugate Vaccine in Infancy: Reactogenicity, Immunogenicity, Immunologic Priming, and Bactericidal Activity against O-Acetylated and De-O-Acetylated Serogroup C Strains

Infection and Immunity ◽

10.1128/iai.69.4.2378-2382.2001 ◽

2001 ◽

Vol 69 (4) ◽

pp. 2378-2382 ◽

Cited By ~ 67

Author(s):

Peter Richmond ◽

Ray Borrow ◽

Jamie Findlow ◽

Sarah Martin ◽

Carol Thornton ◽

...

Keyword(s):

Tetanus Toxoid ◽

Vaccine Development ◽

Geometric Mean ◽

Booster Vaccination ◽

Immunologic Memory ◽

Primary Series ◽

Fourth Dose ◽

Polio Immunization ◽

Bactericidal Activities ◽

Antibody Levels

ABSTRACT The polysaccharide capsule of serogroup C Neisseria meningitidis (MenC) has been integral to vaccine development. Licensed MenC vaccines contain the O-acetylated (OAc+) form of polysaccharide. Some MenC strains have de-O-acetylated (OAc−) polysaccharide, which may affect antibody specificity and functional activity when used in a vaccine. We evaluated an OAc-MenC conjugate-tetanus toxoid conjugate (MCC-TT) vaccine given concomitantly with whole-cell diphtheria-tetanus-pertussis, Haemophilus influenzae type b, and oral polio immunization in 83 infants at 2, 3, and 4 months of age. Serum bactericidal activities (SBA) against OAc+ and OAc− MenC strains and OAc+ and OAc− polysaccharide-specific immunoglobulin G (IgG) levels were evaluated. MCC-TT vaccine was well tolerated. All infants produced SBA titers of ≥8 after a single dose at 2 months of age. The SBA geometric mean titer for OAc+ strain C11 increased from 2.7 (95% confidence interval [CI] 2.2 to 3.2) to 320 (95% CI, 237 to 432), 773 (95% CI, 609 to 982), and 1,063 (95% CI, 856 to 1319) after one, two, and three doses of MCC-TT, respectively. OAc− IgG levels were twice as high as OAc+ IgG levels after the primary series of MCC-TT vaccine, and the SBA was significantly higher against the OAc− MenC strain. Antibody responses to booster vaccination with either OAc+ MenC polysaccharide vaccine (MACP) or a fourth dose of MCC-TT at 14 months of age provided evidence of immunologic memory. The acetylation status of the booster vaccine influenced the specificity of the response, with significantly higher OAc− IgG levels and SBA after MCC-TT vaccine compared to MACP vaccine but similar OAc+ antibody levels. MCC-TT vaccine is highly immunogenic and primes for immunologic memory against OAc+ and OAc− MenC strains in infancy.

Download Full-text

Seroprevalence of Antibody-Mediated, Complement-Dependent Opsonophagocytic Activity against Neisseria meningitidis Serogroup B in England

Clinical and Vaccine Immunology ◽

10.1128/cvi.00100-15 ◽

2015 ◽

Vol 22 (5) ◽

pp. 503-509 ◽

Cited By ~ 5

Author(s):

Holly E. Humphries ◽

Charlotte Brookes ◽

Lauren Allen ◽

Eeva Kuisma ◽

Andrew Gorringe ◽

...

Keyword(s):

Neisseria Meningitidis ◽

Bactericidal Activity ◽

Disease Incidence ◽

Age Group ◽

Serum Samples ◽

Complex Situation ◽

Content Type ◽

Serum Bactericidal Activity ◽

Bactericidal Antibody ◽

Antibody Titers

ABSTRACTThe correlate of protection for the licensure of meningococcal vaccines is serum bactericidal activity. However, evidence indicates that a complex situation and other mechanisms, such as antibody-mediated, complement-dependent opsonophagocytosis (OP), may play a role in protection and should be investigated in order to understand immunity to this disease. In this study, a high-throughput flow cytometric opsonophagocytic assay (OPA) was optimized. The assay measures the presence of killed fluorescently labeledNeisseria meningitidiswithin human granulocytes (differentiated HL60 cells) by flow cytometry, using IgG-depleted pooled human plasma as an exogenous source of complement. This method was found to be reliable and correlated with the results of an opsonophagocytic killing assay. The OPA was used to measure OP activity in 1,878 serum samples from individuals ranging from 0 to 99 years of age againstN. meningitidisstrain NZ98/254 (B:4:P1.7-2,4). The levels of OP activity in individual serum samples varied greatly. OP activity showed an initial peak in the 6- to 12-month age group corresponding to a peak in disease incidence. The OP activity dropped in childhood until the late teenage years, although there was still a higher percentage of individuals with OP activity than with protective bactericidal antibody titers. OP activity reached a peak in the 30- to 39-year age group and then declined. This later peak in OP activity did not coincide with the young adults in whom peak serum bactericidal activity and disease incidence occurred. The demonstration of OP activity when disease incidence is low and when protective bactericidal antibody titers are not detected may indicate a role for OP in protection from meningococcal disease in these age groups.

Download Full-text

Optimization and Application of a Multiplex Bead-Based Assay To Quantify Serotype-Specific IgG against Streptococcus pneumoniae Polysaccharides: Response to the Booster Vaccine after Immunization with the Pneumococcal 7-Valent Conjugate Vaccine

Clinical and Vaccine Immunology ◽

10.1128/cvi.00408-09 ◽

2010 ◽

Vol 17 (4) ◽

pp. 674-682 ◽

Cited By ~ 46

Author(s):

Karin E. M. Elberse ◽

Irina Tcherniaeva ◽

Guy A. M. Berbers ◽

Leo M. Schouls

Keyword(s):

Conjugate Vaccine ◽

Geometric Mean ◽

Booster Vaccination ◽

Cross Reactivity ◽

Serum Samples ◽

Primary Series ◽

Reference Serum ◽

Specific Igg ◽

Protective Threshold ◽

Multiplex Bead

ABSTRACT We describe the optimization and application of a multiplex bead-based assay (Luminex) to quantify antibodies against polysaccharides of 13 pneumococcal serotypes. In the optimized multiplex immunoassay (MIA), intravenous immune globulin was introduced as an in-house reference serum, and nonspecific reacting antibodies were adsorbed with the commercial product pneumococcal C polysaccharides Multi. The antibody concentrations were assessed in 188 serum samples obtained pre- and post-booster vaccination at 11 months after administration of a primary series of the pneumococcal seven-valent conjugate vaccine (PCV-7) at 2, 3, and 4 months of age. The results of the MIA were compared with those of the ELISA for the serotypes included in the seven-valent conjugated polysaccharide vaccine and for a non-vaccine serotype, serotype 6A. The geometric mean concentrations of the antibodies determined by MIA were slightly higher than those determined by ELISA. The correlations between the assays were good, with R 2 values ranging from 0.84 to 0.91 for all serotypes except serotype 19F, for which R 2 was 0.70. The concentrations of antibody against serotype 6A increased after the administration of PCV-7 due to cross-reactivity with serotype 6B. The differences between the results obtained by ELISA and MIA suggest that the internationally established protective threshold of 0.35 μg/ml should be reevaluated for use in the MIA and may need to be amended separately for each serotype.

Download Full-text

Immunogenicity and Safety of a Meningococcal Quadrivalent Conjugate Vaccine in Saudi Arabian Adolescents Previously Vaccinated with One Dose of Bivalent and Quadrivalent Meningococcal Polysaccharide Vaccines: a Phase III, Controlled, Randomized, and Modified Blind-Observer Study

Clinical and Vaccine Immunology ◽

10.1128/cvi.00039-12 ◽

2012 ◽

Vol 19 (7) ◽

pp. 999-1004 ◽

Cited By ~ 6

Author(s):

Yagob Al-Mazrou ◽

Mohamed Khalil ◽

Helen Findlow ◽

Helen Chadha ◽

Valerie Bosch Castells ◽

...

Keyword(s):

Conjugate Vaccine ◽

Geometric Mean ◽

Saudi Arabian ◽

Polysaccharide Vaccine ◽

Exposed Group ◽

Phase Iii ◽

Rabbit Serum ◽

Serum Samples ◽

Naive Group ◽

Bactericidal Antibody

ABSTRACTReduced immune responses to repeated polysaccharide vaccination have been previously reported, but there are limited immunogenicity data on the use of meningococcal polysaccharide vaccine (PSV) followed by meningococcal conjugate vaccine. Saudi Arabian adolescents (aged 16 to 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, randomized, and modified observer-blind study (collectively termed the PSV-exposed group). The PSV-exposed group was randomized to receive either quadrivalent meningococcal conjugate vaccine (MCV4) (n= 145 PSV-exposed/MCV4 group) or MPSV4 (n= 142 PSV-exposed/MPSV4 group), and a PSV-naïve group received MCV4 (n= 163). Serum samples collected prevaccination and 28 days postvaccination were measured by baby rabbit serum bactericidal antibody (rSBA) assay, and vaccine tolerability and safety were also evaluated. For each serogroup, the postvaccination geometric mean titers (GMTs) were significantly higher in the PSV-naïve group than in either group comprised of the PSV-exposed participants. The postvaccination serogroup C rSBA GMT was significantly higher in the PSV-MCV4 group than in the PSV-MPSV4 group after adjusting for prevaccination GMTs. Although not statistically significant, similar differences were observed for serogroups A, Y, and W-135. No worrisome safety signals were detected. This study demonstrated MCV4 to be safe and immunogenic in those who had previously received polysaccharide vaccination, and it suggests that conjugate vaccine can partially compensate for the hyporesponsiveness seen with repeated doses of polysaccharide vaccine.

Download Full-text

Kinetics of Meningococcal Serogroup C-Specific Functional Antibody Levels Up to 15 Years after a Single Immunization with a Meningococcal Serogroup C Conjugate Vaccine during Adolescence

Clinical and Vaccine Immunology ◽

10.1128/cvi.00429-16 ◽

2016 ◽

Vol 24 (2) ◽

Author(s):

Susanne P. Stoof ◽

Mariëtte B. van Ravenhorst ◽

Debbie M. van Rooijen ◽

Richarda M. de Voer ◽

Fiona R. M. van der Klis ◽

...

Keyword(s):

Mixed Model ◽

Linear Mixed Model ◽

Primary Vaccination ◽

Serum Samples ◽

Cross Sectional ◽

Key Factor ◽

Bactericidal Antibody ◽

Adolescent Vaccination ◽

Antibody Levels ◽

Antibody Kinetics

ABSTRACT Adolescent vaccination is now considered the key factor for offering direct protection against meningococcal disease but also for reducing carriage and transmission and, in this way, establishing herd protection. This study estimated age-dependent patterns in functional meningococcal serogroup C (MenC) antibody kinetics after primary MenC conjugate (MenCC) vaccination in adolescents. Serum samples (n = 1,676) were drawn from 2006 to 2011 from individuals aged 9 to 18 years at the time of primary MenCC vaccination in 2002. Functional antibody levels were measured with a serum bactericidal antibody assay (SBA) using rabbit complement. SBA titers gradually declined with time. Up to 9 years after primary vaccination, SBA titers were estimated to be higher in individuals who were aged 13 to 18 years at priming than in those who were aged 9 to 10 years at priming. Based on a linear mixed model, the higher functional antibody levels with age seem to be due to the achievement of higher peak levels upon vaccination rather than to lower rates of decline. It is estimated that 35 to 50% of individuals who received a single primary MenCC vaccination at an age of 9 to 18 years in 2002 will still have sufficient protective antibody levels 15 years later. Using a linear mixed model based on cohort data for a single dated serum sample per person, we were able to estimate the level of protection against MenC up to 15 years after a single vaccination. The current study shows that analysis of antibody kinetics can be done using cross-sectional serology data and is therefore relevant for future serosurveillance studies.

Download Full-text