Propositive follow-up: Long-term immune responses to the 4CMenB and MenACWY vaccines in people living with HIV.

BACKGROUND: People living with HIV have an increased risk of meningococcal disease. The Propositive trial evaluated co-administration of two doses of a four-component recombinant protein-based MenB vaccine (4CMenB) and a quadrivalent conjugate polysaccharide MenACWY vaccine (MenACWY-CRM197) given 1 month apart in people with HIV. The follow-up trial assessed the immunogenicity of these vaccines at 1.5 and 2.5 years after primary vaccination. METHODS: Participants who completed the parent Propositive trial were invited to the follow-up study. Immunogenicity analysis was performed at 18 and 30 months after primary vaccination. Primary outcome measures were serum bactericidal antibody (SBA) geometric mean titres (GMTs) against three MenB reference strains and the proportion of participants maintaining a protective SBA titre of ≥4 at 18 and 30 months. Secondary outcome measures were SBA GMTs against MenA, C, W, and Y serogroups and the proportion of participants maintaining a protective SBA titre of ≥8 at 18 and 30 months. The trial is registered with Clinicaltrials.gov (NCT042394300). RESULTS: A total of 40 participants aged 22-47 years were enrolled. Geometric mean titres waned by 18 and 30 months but remained higher than pre-vaccination for all MenB strains and MenA, C, W, and Y. In total, 75%-85% of participants retained protective SBA titres by 30 months against individual MenB strains, whereas 68.8% of patients retained protective antibody titres against all three MenB strains. Antibodies against MenC waned more rapidly than did those against MenA, W, and Y. The proportion of participants with protective titres against MenC at 30 months was also lower (46.9%) than that with protective titres against MenA (87.5%), W (78.1%), and Y (87.5%). CONCLUSIONS: Immune responses against MenB in our cohort of people living with HIV at 2.5 years of follow-up were reassuring, with 68.8% of participants retaining protection against all three reference strains. However, responses against MenC were lower than those against MenA, W, and Y serogroups.

Immunogenicity of a single 4CMenB vaccine booster in adolescents 11 years after childhood immunisation.

The clinical development of the meningococcal vaccine, 4CMenB, included 2 doses in vaccine-naïve adolescents, which was considered unlikely to be cost-effective for implementation. Theoretically, priming with 4CMenB in early childhood might drive strong immune responses after only a single booster dose in adolescents and reduce programmatic costs. To address this question, children over 11 years old who took part in previous trials involving the administration of 3-5 doses of 4CMenB at infant/preschool age from 2006 were recruited into a post licensure single-centre trial, and were divided into two groups: those who received their last dose at 12 months old (infant group) and those who received their last dose at 3 years old (infant + preschool group). Naïve age-matched controls were randomised to receive one (adolescent 1 group) or two doses at days 0 and 28 (adolescent 2 group) of 4CMenB. Serum bactericidal antibody (SBA) assays using human complement were performed against three reference strains prior to vaccination, and at 1, 6 and 12 months. Previous vaccination was associated with a higher response to a single booster dose at 11 years of age, one-month post-vaccination, when compared with a single dose in naïve age-matched controls. At day 180, the highest responses were observed in participants in the infant + preschool group against strain 5/99 (GMT 316.1 [CI 158.4 to 630.8]), as compared with naïve adolescents who received two doses (GMTs 84.5 [CI 57.7 to 123.6]). When the last dose was received at 12-months of age, responses to a single adolescent dose were not as robust (GMT 61.1 [CI 14.8 to 252.4] to strain 5/99). This descriptive study indicates that the highest SBA responses after a single dose in adolescence were observed in participants who received a preschool dose, suggesting that B cell memory responses are not sufficiently primed at less than 12 months of age. Trial registration EudraCT 2017-004732-11, ISRCTN16774163.

If all planning is local, how are we going to save tomorrow? Ten pragmatic lessons from the field.

This monograph presents practical lessons learned from more than 40 years of professional and academic experience in ecological and community land use planning within the New York's Adirondack-Champlain-Catskills Regions, the Northern Forest of Maine, Vermont, New Hampshire and New York, and the Northern Appalachian/Acadian Ecoregion. The intention is to share catalytic, synergistic, and interdisciplinary field lessons from the author's firsthand experiences for the benefit of renaissance communities, researchers, and practitioners seeking new beginnings and stimulation of new thinking beyond their sightlines. Lessons are presented in ten areas [1] integrating legal, ethical, and natural considerations; [2] recognizing diverse types of land ownership; [3] discovering shared ethics and values; [4] modernizing planning practice; [5] using Participatory Action Research (PAR); [6] working with limited access to science, technology, and planning resources; [7] using science to inform and enlighten the planning process; [8] riding the coattails of popular movements; [9] recognizing human relationships with natural environments; and [10] educating and informing citizens as a force for nature. These ten lessons, contextualized within Critical Theory and Participatory Action Research (PAR), lead the author to an "inflective" PAR paradigm for land use planning that links planning, participation, and science. Perhaps, just perhaps, through a shared context of place-tomorrow can be saved.

Invasive serogroup B meningococci in England following three years of 4CMenB vaccination - First real-world data.

OBJECTIVES: In 2015 the UK became the first country to implement the meningococcal B (MenB) vaccine, 4CMenB, into the national infant program. 4CMenB is expected to cover meningococci expressing sufficient levels of cross-reactive proteins. This study presents clonal complex, 4CMenB antigen genotyping, and 4CMenB coverage data for all English invasive MenB isolates from 2014/15 (1 year pre-vaccine) through 2017/18 and compares data from vaccinated and unvaccinated ≤3 year olds. METHODS: Vaccine coverage of all invasive MenB isolates from 2014/15 to 2017/18 (n = 784) was analysed using the Meningococcal Antigen Typing System. Genotyping utilised the Meningococcus Genome Library. RESULTS: Among ≤3 year olds, proportionally fewer cases in vaccinees (1, 2 or 3 doses) were associated with well-covered strains e.g. cc41/44 (20.5% versus 36.4%; P<0.01) and antigens e.g. PorA P1.4 (7.2% versus 17.3%; P = 0.02) or fHbp variant 1 peptides (44.6% vs 69.1%; P<0.01). Conversely, proportionally more cases in vaccinees were associated with poorly-covered strains e.g. cc213 (22.9% versus 9.6%; P<0.01) and antigens e.g. variant 2 or 3 fHbp peptides (54.2% versus 30.9%; P<0.01). CONCLUSIONS: 4CMenB reduces disease due to strains with cross-reactive antigen variants. No increase in absolute numbers of cases due to poorly covered strains was observed in the study period.

Immunogenicity of the UK group B meningococcal vaccine (4CMenB) schedule against groups B and C meningococcal strains (Sched3): outcomes of a multicentre, open-label, randomised controlled trial.

BACKGROUND: The use of the multicomponent meningococcal vaccine 4CMenB in the UK schedule at 2, 4, and 12 months of age has been shown to be 59·1% effective at preventing invasive group B meningococcal disease. Here, we report the first data on the immunogenicity of this reduced-dose schedule to help to interpret this effectiveness estimate. METHODS: In this multicentre, parallel-group, open-label, randomised clinical trial, infants aged up to 13 weeks due to receive their primary immunisations were recruited via child health database mailouts in Oxfordshire and via general practice surgeries in Gloucestershire and Hertfordshire. Infants were randomly assigned (1:1) with permuted block randomisation to receive a 2 + 1 (2, 4, and 12 months; group 1) or 1 + 1 (3 and 12 months; group 2) schedule of the 13-valent pneumococcal conjugate vaccine (PCV13). All infants also received 4CMenB at 2, 4, and 12 months of age, and had blood samples taken at 5 and 13 months. Participants and clinical trial staff were not masked to treatment allocation. Proportions of participants with human complement serum bactericidal antibody (hSBA) titres of at least 4 were determined for group B meningococcus (MenB) reference strains 5/99 (Neisserial Adhesin A [NadA]), NZ98/254 (porin A), and 44/76-SL (factor H binding protein [fHbp]). Geometric mean titres (GMTs) with 95% CIs were also calculated, and concomitant vaccine responses (group C meningococcus [MenC], Haemophilus influenzae b [Hib], tetanus, diphtheria, and pertussis) were compared between groups. The primary outcome was PCV13 immunogenicity, with 4CMenB immunogenicity and reactogenicity as secondary outcomes. All individuals by randomised group with a laboratory result were included in the analysis. The study is registered on the EudraCT clinical trials database, 2015-000817-32, and ClinicalTrials.gov, NCT02482636, and is complete. FINDINGS: Between Sept 22, 2015, and Nov 1, 2017, of 376 infants screened, 213 were enrolled (106 in group 1 and 107 in group 2). 204 samples post-primary immunisation and 180 post-boost were available for analysis. The proportion of participants with hSBA of at least 4 was similar in the two study groups. For strain 5/99, all participants developed hSBA titres above 4 in both groups and at both timepoints. For strain 44/76-SL, these proportions were 95·3% (95% CI 88·5-98·7) or above post-priming (82 of 86 participants in group 1), and 92·4% (84·2-97·2) or above post-boost (73 of 79 participants in group 1). For strain NZ98/254, these proportions were 86·5% (78·0-92·6) or above post-priming (83 of 96 participants in group 2) and 88·6% (79·5-94·7) or above post-boost (70 of 79 participants in group 1). The MenC rabbit complement serum bactericidal antibody (rSBA) titre in group 1 was significantly higher than in group 2 (888·3 vs 540·4; p=0·025). There was no significant difference in geometric mean concentrations between groups 1 and 2 for diphtheria, tetanus, Hib, and pertussis post-boost. A very small number of children did not have a protective response against 44/76-SL and NZ98/254. Local and systemic reactions were similar between the two groups, apart from the 3 month timepoint when one group received an extra dose of PCV13 and recorded more systemic reactions. INTERPRETATION: These data support the recent change to the licensed European schedule for 4CMenB to add an infant 2 + 1 schedule, as used in the routine UK vaccine programme with an effectiveness of 59·1%. When compared with historical data, our data do not suggest that effectiveness would be higher with a 3 + 1 schedule, however a suboptimal boost response for bactericidal antibodies against vaccine antigen fHbp suggests a need for ongoing surveillance for vaccine breakthroughs due to fHbp-matched strains. Changing from a 2 + 1 to a 1 + 1 schedule for PCV13 for the UK is unlikely to affect protection against diphtheria, tetanus, and Hib, however an unexpected reduction in bactericidal antibodies against MenC seen with the new schedule suggests that ongoing surveillance for re-emergent MenC disease is important. FUNDING: Bill & Melinda Gates Foundation and the National Institute for Health Research.

The Effect of Evaluator Training on Inter- and Intrarater Reliability in High-Stakes Assessment in Simulation.

AIM: The aim of this study was to evaluate the effectiveness of a training intervention in achieving inter- and intrarater reliability among faculty raters conducting high-stakes assessment of clinical performance in simulation. BACKGROUND: High-stakes assessment of simulation performance is being adopted in nursing education. However, limited research exists to guide best practices in training raters, which is essential to ensure fair and defensible assessment. METHOD: A nationwide sample of 75 prelicensure RN program faculty participated in an experimental, randomized, controlled study. RESULTS: Participants completing a training intervention achieved higher inter- and intrarater reliability than control group participants when using a checklist evaluation tool. Mixed results were achieved by participants when completing a global competency assessment. CONCLUSION: The training intervention was effective in helping participants to achieve a shared mental model for use of a checklist, but more time may be necessary to achieve consistent global competence decisions.

Developing a revised definition of the Bobath concept: Phase three.

OBJECTIVE: To develop a revised definition of the Bobath concept that incorporates the perspectives of members of the International Bobath Instructors Training Association (IBITA). METHODS: A three-phase consensus building design utilizing (i) focus groups; (ii) survey methods; and, (iii) real-time Delphi. This paper presents the findings from the real-time Delphi, an iterative process to collect and synthesize expert opinions anonymously, provide controlled feedback, with the overall goal of achieving consensus. RESULTS: One hundred and twenty-one IBITA members participated in the real-time Delphi. Over three Delphi Rounds, consensus was reached on six overarching conceptual statements and 11 statements representing unique aspects of Bobath clinical practice. One statement that aimed to describe the Bobath clinical term of "placing" was eliminated in Round One due to participant reservations that a text description was insufficient for this term. Seven statements underwent minor wording revisions in Round Two and Three to improve sentence clarity. CONCLUSION: Using the real-time Delphi, we were successful in gaining consensus in an expert group on a series of statements on which a revised definition of the Bobath concept could be based.

The Bobath concept - a model to illustrate clinical practice.

Background and purpose: The model of Bobath clinical practice provides a framework identifying the unique aspects of the Bobath concept in terms of contemporary neurological rehabilitation. The utilisation of a framework to illustrate the clinical application of the Bobath concept provides the basis for a common understanding with respect to Bobath clinical practice, education, and research. The development process culminating in the model of Bobath clinical practice is described. Case description: The use of the model in clinical practice is illustrated using two cases: a client with a chronic incomplete spinal cord injury and a client with a stroke. Discussion: This article describes the clinical application of the Bobath concept in terms of the integration of posture and movement with respect to the quality of task performance, applying the Model of Bobath Clinical Practice. Facilitation, a key aspect of Bobath clinical practice, was utilised to positively affect motor control and perception in two clients with impairment-related movement problems due to neurological pathology and associated activity limitations and participation restrictions - the outcome measures used to reflect the individual clinical presentation. Implications for Rehabilitation The model of Bobath clinical practice provides a framework identifying the unique aspects of the Bobath-concept. The model of Bobath clinical practice provides the basis for a common understanding with respect to Bobath clinical practice, education, and research. The clinical application of the Bobath-concept highlights the integration of posture and movement with respect to the quality of task performance. Facilitation, a key aspect of Bobath clinical practice, positively affects motor control, and perception.

Developing a revised definition of the Bobath concept.

OBJECTIVE: This study was developed as a consensus-building exercise within the International Bobath Instructors Training Association (IBITA) to develop a revised definition of the Bobath concept. METHODS: A three-phase design utilizing (a) focus groups, (b) survey methods, and, (c) real-time Delphi. This paper details Phase 1 and 2. RESULTS: Forty IBITA members participated in five focus groups. Eight broad themes were developed from the focus groups from which the survey statements were developed. There was a high level of agreement on all nine survey statements identifying overarching constructs and on 12 of the 13 statements identifying unique aspects of Bobath clinical practice. Lower scores were attributed to lack of understanding of the term humanistic, Bobath clinical practice addressing multiple domains such as impairments, activities, and participation and limited agreement on the description of the term "placing." CONCLUSION: Focus groups and a web-based survey were successful in soliciting the opinions of IBITA members on themes and statements of importance for the development of a revised Bobath definition. The results of Phase 1 and 2 will inform Phase 3, a real-time Delphi, to gain consensus within IBITA on statements on which a revised Bobath definition is to be based.

Influence of a Patient-Centered Care Coordination Clinical Module on Student Learning: A Multimethod Study.

BACKGROUND: This article reports the results of a study that investigated the influence of an integrated patient centered care coordination (PCCC) clinical curricular module on nursing student learning outcomes. Baccalaureate nursing education must increase its emphasis on the professional nursing role of care coordination to meet changing health care needs, including the ability to practice in community and ambulatory care settings. Little research has been conducted to examine the effect of curricular change for teaching care coordination on student learning outcomes. METHOD: This study used a quasi-experimental mixed-methods design at a university school of nursing, collecting data with a pre-postsurvey, a skills performance instrument, and focus groups. RESULTS: The PCCC curricular module significantly and positively affected student learning outcomes, as evidenced by the pre-postsurvey and focus group results. CONCLUSION: Intentional curricular change can make a significant impact on students' knowledge, attitudes, and behaviors related to PCCC. [J Nurs Educ. 2017;56(1):6-11.].

Consensus on Exercise Reporting Template (CERT): Modified Delphi Study.

BACKGROUND: Exercise interventions are often incompletely described in reports of clinical trials, hampering evaluation of results and replication and implementation into practice. OBJECTIVE: The aim of this study was to develop a standardized method for reporting exercise programs in clinical trials: the Consensus on Exercise Reporting Template (CERT). DESIGN AND METHODS: Using the EQUATOR Network's methodological framework, 137 exercise experts were invited to participate in a Delphi consensus study. A list of 41 items was identified from a meta-epidemiologic study of 73 systematic reviews of exercise. For each item, participants indicated agreement on an 11-point rating scale. Consensus for item inclusion was defined a priori as greater than 70% agreement of respondents rating an item 7 or above. Three sequential rounds of anonymous online questionnaires and a Delphi workshop were used. RESULTS: There were 57 (response rate=42%), 54 (response rate=95%), and 49 (response rate=91%) respondents to rounds 1 through 3, respectively, from 11 countries and a range of disciplines. In round 1, 2 items were excluded; 24 items reached consensus for inclusion (8 items accepted in original format), and 16 items were revised in response to participant suggestions. Of 14 items in round 2, 3 were excluded, 11 reached consensus for inclusion (4 items accepted in original format), and 7 were reworded. Sixteen items were included in round 3, and all items reached greater than 70% consensus for inclusion. LIMITATIONS: The views of included Delphi panelists may differ from those of experts who declined participation and may not fully represent the views of all exercise experts. CONCLUSIONS: The CERT, a 16-item checklist developed by an international panel of exercise experts, is designed to improve the reporting of exercise programs in all evaluative study designs and contains 7 categories: materials, provider, delivery, location, dosage, tailoring, and compliance. The CERT will encourage transparency, improve trial interpretation and replication, and facilitate implementation of effective exercise interventions into practice.

Enhancing Clinical Reasoning Through Simulation Debriefing: A Multisite Study.

AIM: The aim of this research was to replicate Dreifuerst's 2012 findings of enhanced clinical reasoning scores using a structured debriefing: Debriefing for Meaningful Learning (DML). BACKGROUND: The direct effect of debriefing on clinical reasoning is not well studied. The nursing education literature supports debriefing as a reflective dialogue necessary to enhance clinical reasoning. METHOD: A quasi-experimental, pretest-posttest, repeated measure research design was used to evaluate nursing students' clinical reasoning using the Health Sciences Reasoning Test (HSRT). RESULTS: The change in HSRT mean scores was determined to be significant for the intervention group at the .05 level and insignificant for the control group. The change in HSRT mean scores between the intervention and control groups was determined to be significant at the .10 level. CONCLUSION: Nursing students who had the DML debriefing scored significantly higher in their clinical reasoning than nursing students who had usual and customary debriefing.

The lived experience of teaching about race in cultural nursing education.

PURPOSE: Some nursing scholars assert that race and racism require a more explicit focus in cultural nursing education if the profession is to positively impact health care disparities. This study explored what White BSN cultural educators think, believe, and teach about race, racism, and antiracism. METHOD: Phenomenological methods were used to analyze interview data from 10 White BSN faculty members who taught cultural content. FINDINGS: Four themes were identified: living and learning in White spaces, a personal journey toward antiracism, values transformed through personal relationship, and race at the margins. DISCUSSION/CONCLUSIONS: Whiteness obscured the participants' understanding and teaching of race; White nursing faculty were not well prepared to teach about race and racism; learning about these topics occurs best over time and through personal relationships. IMPLICATIONS: Faculty development regarding race and racism is needed to facilitate student, curricular, and institutional change.

Evaluation of the safety and immunogenicity in United Kingdom laboratory workers of a combined Haemophilus influenzae type b and meningococcal capsular group C conjugate vaccine.

BACKGROUND: Although a combined Haemophilus influenzae type b (Hib)/meningococcal capsular group C (MenC) conjugate vaccine with a tetanus toxoid carrier protein (Hib/MenC-TT) is not licensed for use in those above 2 years of age due to lack of data on safety and efficacy, certain patient groups at high risk of MenC and/or Hib disease are recommended to receive it. Laboratory workers working with Hib and/or MenC cultures may be at a potentially increased risk of acquiring infectious diseases and vaccination is therefore an important safety consideration. We undertook a clinical trial to investigate the safety and immunogenicity of Hib/MenC-TT vaccine in this cohort. METHODS: A total of 33 subjects were recruited to the trial, all of whom were vaccinated. Serology was completed on samples taken at baseline and four weeks following vaccination to determine MenC specific IgG, MenC serum bactericidal antibody (SBA), anti-Hib polyribosylribitol phosphate (PRP) IgG and anti-tetanus toxoid IgG responses. RESULTS: At baseline, high proportions of subjects had protective antibody concentrations against MenC, Hib and tetanus due to previous vaccination and/or natural exposure. Vaccination induced > 3, 10 and 220 fold increases in geometric mean concentrations for MenC SBA, anti-tetanus toxoid IgG and anti-Hib PRP IgG, respectively. Following vaccination, 97% of subjects had putative protective SBA titres ≥ 8, 100% had short term protective anti-Hib PRP IgG concentrations ≥ 0.15 µg/mL and 97% had protective anti-tetanus toxoid concentrations ≥ 0.1 IU/mL. No safety concerns were reported with minor local reactions being reported by 21% of subjects. CONCLUSIONS: Immunological responses determined in this trial are likely a combination of primary and secondary responses due to previous vaccination and natural exposure. Subjects were a representative cross-section of laboratory workers, enabling us to conclude that a single dose of Hib/MenC-TT was safe and immunogenic in healthy adults providing the evidence that this vaccine may be used for providing protection in an occupational setting.

Multicenter, open-label, randomized phase II controlled trial of an investigational recombinant Meningococcal serogroup B vaccine with and without outer membrane vesicles, administered in infancy.

BACKGROUND: In the absence of an efficacious broadly protective vaccine, serogroup B Neisseria meningitidis (MenB) is the leading cause of bacterial meningitis and septicemia in many industrialized countries. An investigational recombinant vaccine that contains 3 central proteins; Neisserial adhesin A (NadA), factor H binding protein (fHBP) and Neisserial heparin binding antigen (NHBA) has been developed. These antigens have been formulated with and without outer membrane vesicles (rMenB+OMV and rMenB, respectively) from the New Zealand epidemic strain (B:4:P1.7-2,4). In this trial, we assessed the immunogenicity of these formulations in infants, who are at greatest risk of contracting MenB disease. METHODS: A total of 147 infants from the United Kingdom were enrolled and randomly assigned to receive rMenB or rMenB+OMV at 2, 4, 6, and 12 months of age or a single dose at 12 months of age. Serum samples taken before and after vaccination were assayed in a standardized serum bactericidal antibody assay against 7 MenB strains. Local and systemic reactogenicity were recorded for 7 days after each vaccination. Analysis was according to protocol. RESULTS: After 3 doses, both vaccines were immunogenic against strains expressing homologous or related NadA and fHBP. rMenB+OMV demonstrated greater immunogenicity than did rMenB and was immunogenic against strains expressing homologous PorA. Both vaccines elicited anamnestic responses after the fourth dose. For both vaccines, responses were lower against strains expressing heterologous fHBP variants and after a single dose at 12 months. CONCLUSIONS: The rMenB+OMV vaccine has the potential to protect infants from MenB disease, although the breadth of protection afforded to heterologous antigens requires additional investigation.

Seroprevalence of antibodies against serogroup C meningococci in England in the postvaccination era.

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 > or =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 > or =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.

Comparison of phenotypically indistinguishable but geographically distinct Neisseria meningitidis Group B isolates in a serum bactericidal antibody assay.

The "gold standard" assay for measuring serologic protection against Neisseria meningitidis group B (MenB) is the serum bactericidal antibody (SBA) assay. Of vital importance to the outcome of the SBA assay is the choice of the target strain(s), which is often chosen on the basis of phenotype or genotype. We therefore investigated the effect on the results produced by the SBA assay of using phenotypically indistinguishable but geographically distinct MenB isolates. Nine PorA P1.19,15 and 11 PorA P1.7-2,4 MenB isolates were incorporated into the SBA assay using human complement and were assayed against sera obtained either before or after outer membrane vesicle vaccination. Large differences in the results produced by the isolates in the SBA assay were demonstrated. These included differences as great as 5.8-fold in SBA geometric mean titers and in the proportions of subjects with SBA titers of >/=4. Ranges of as many as 9 SBA titers were achieved by individual sera across the panels of isolates. To determine the reasons for the differences observed, investigations into the expression of capsular polysaccharide, PorA, PorB, Opc, and lipooligosaccharide (LOS) and into LOS sialylation were completed. However, minor differences were found between strains, indicating similar expression and no antigen masking. These results have implications for the choice of MenB target strains for inclusion in future studies of MenB vaccines and highlight the requirement for standardization of target strains between laboratories.

Seroprevalence of bactericidal and anti-outer membrane vesicle antibodies to Neisseria meningitidis group B in England.

Outer membrane vesicle (OMV) and recombinant protein-based vaccines targeted against multiple strains of group B meningococci are under development. The serum bactericidal antibody (SBA) assay has been designated the surrogate of protection, but the exact cutoff has not been determined. We measured the SBA titers in 2,415 serum samples and the anti-OMV IgG antibody concentrations in 2,672 serum samples representative of the English population to establish a baseline of natural immunity. SBA and anti-OMV IgG antibody titers are high in infants in the first 3 months of life, declining thereafter, presumably as maternal immunity wanes. About 6% of the subjects in the 1- to 11-year-old age group had SBA titers >or=4. During the teenage years, there was a marked increase in the percentage of subjects with SBA titers >or=4, rising to over 50% in 19-year-olds, with about 20% of older adults achieving this titer. The peak in SBA and anti-OMV IgG titers coincided with the peak in meningococcal carriage. Simple mathematical models confirm that the relationship between observed seroprevalence and carriage by age is consistent with carriage inducing SBA and that following an episode of carriage, SBA levels may remain elevated for many months. With the exception of children aged 3 to 11 months, there was no clear relationship between disease incidence and seroprevalence.