Development of a large scale human complement source for use in bacterial immunoassays

Brookes, Charlotte; Kuisma, Eeva; Alexander, Frances; Allen, Lauren; Tipton, Thomas; Ram, Sanjay; Gorringe, Andrew; Taylor, Stephen

doi:10.1016/j.jim.2013.02.007

Cited by 18 publications

(15 citation statements)

References 53 publications

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“…Serum from untreated agammaglobulinemic patients is potentially a good complement source for bactericidal assays but is too rarely available to offer a practical solution for large-scale vaccine evaluation. The depletion of IgG from pooled plasma donations has been explored as an alternative and may become an option for the evaluation of SBA responses during the clinical development of future vaccines (40). In the absence of an alternative, however, antibody responses to the 4CMenB and bivalent rLP2086 vaccines were evaluated using sera screened for their lack of reactivity to the isolate used in the assay.…”

Section: Assessing and Predicting Efficacymentioning

confidence: 99%

Recent Progress in the Prevention of Serogroup B Meningococcal Disease

Feavers

Maiden

2017

Clin Vaccine Immunol

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The widespread use of meningococcal polysaccharide conjugate vaccines has highlighted the challenge of providing protection against serogroup B disease. Over a period of 4 decades, vaccine development has focused on subcapsular protein antigens, first with outer membrane vesicle (OMV) vaccines against epidemic outbreaks, and more recently on new multicomponent vaccines designed to offer better cross-protection against the antigenically diverse strains responsible for endemic disease. Because of the low incidence of meningococcal disease, the protective efficacy of these vaccines has not been determined in clinical studies, and their licensure has been based on serological data; however, the serological assays used to predict protective coverage have limitations. As a result, evidence of the effectiveness of these vaccines against different strains and the contribution of specific antigens to protection can only be provided by epidemiological analyses following their implementation in sufficiently large populations. The recent inclusion of the four-component meningococcal serogroup B (4CMenB) vaccine, Bexsero, in the infant immunization program in the UK has provided preliminary evidence that the vaccine is effective. Ongoing surveillance will provide valuable data on its longer-term impact and antigenic coverage. Further development of protein-based vaccines against meningococcal disease is anticipated to improve antigenic coverage and adjust to changes in circulating strains. At the same time, alternative immunization strategies may be explored to improve overall vaccine effectiveness by, for example, protecting the youngest infants or providing herd protection.

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Section: Assessing and Predicting Efficacymentioning

confidence: 99%

Recent Progress in the Prevention of Serogroup B Meningococcal Disease

Feavers

Maiden

2017

Clin Vaccine Immunol

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“…In an attempt to circumvent these difficulties, a group at Public Health England (PHE) in the UK has developed a method for IgG-depletion of 300 mL batches of pooled human lepirudinderived plasma using Protein G sepharose affinity chromatography that retains complement activity [83]. Although the methodology depleted C1q, they eluted this from the affinity matrix, concentrated it and added it to the complement source.…”

Section: Technical Solutions To Complement Problemsmentioning

confidence: 99%

Serum bactericidal antibody assays – The role of complement in infection and immunity

McIntosh

Bröker

Wassil³

et al. 2015

Vaccine

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“…As mentioned above, the standardization of the assay was aided by the use of pooled IgG-depleted human plasma as the source of complement (28). SBAs for serogroup B meningococci are generally performed using human complement, but finding human donors with sufficiently low anti-meningococcal serum antibodies is a considerable problem (34) that is solved by the IgG-depleted complement source used here.…”

Section: Discussionmentioning

confidence: 99%

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

Humphries¹,

Brookes²,

Allen³

et al. 2015

Clin. Vaccine Immunol.

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The 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 labeled Neisseria meningitidis within human granulocytes (differentiated HL60 cells) by flow cytometry, using IgGdepleted 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 against N. meningitidis strain 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.T he correlate of protection for the licensure of meningococcal vaccines is serum bactericidal activity, as measured by the serum bactericidal assay (SBA). This was established by direct evidence obtained in studies carried out in the 1960s by Goldschneider (1), who observed an epidemic of serogroup C meningococcal disease in military recruits. In this study, while 82% of the military recruits had SBA titers of Ն1:4 at the start of their basic training, 51 out of 53 recruits who developed meningococcal disease had SBA titers of Ͻ1:4 against the epidemic strain. Thus, it was proposed that a titer of Ն1:4 conferred protection against disease (1). In a concurrent paper by Goldschneider (2), it was also observed that SBA titers of Ն1:4 were rarely observed in children between 6 and 12 months of age, which is the age group with the highest incidence of meningococcal disease.However, there is evidence to suggest that protection from meningococcal disease is possible even in the absence of an SBA titer of Ն1:4 (reviewed by Granoff [3]). Even in the initial reports by Goldschneider (1, 2), it was noted that there were many recruits who were likely to have been exposed to the epidemic strain and had SBA titers of Ͻ1:4 but did not develop meningococcal disease (1). Therefore, wh...

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Development of a large scale human complement source for use in bacterial immunoassays

Cited by 18 publications

References 53 publications

Recent Progress in the Prevention of Serogroup B Meningococcal Disease

Recent Progress in the Prevention of Serogroup B Meningococcal Disease

Serum bactericidal antibody assays – The role of complement in infection and immunity

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

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