Importance of circulating antibodies in protection against meningococcal disease

Erlich, Kim S.; Congeni, Blaise L.

doi:10.4161/hv.20473

Cited by 17 publications

(9 citation statements)

References 53 publications

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“…To prevent this invasive and potentially devastating infection, sufficient levels of functional antibodies in serum have been shown to be important [1]. Protective levels of antibodies in cases invasive infection are achieved only after several days [2], whereas the meningococcus can be fatal within hours after invasion in the bloodstream. Meningococcal polysaccharide (PS) conjugate vaccines (MCVs) are able to induce functional bactericidal serum antibodies that, upon binding to invading meningococci, activate complement leading to lysis of the bacteria and enhanced phagocytosis [3, 4].…”

Section: Introductionmentioning

confidence: 99%

Use of saliva to monitor meningococcal vaccine responses: proposing a threshold in saliva as surrogate of protection

Ravenhorst

Klis

Rooijen

et al. 2019

BMC Med Res Methodol

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BackgroundMucosal antibodies against capsular polysaccharides offer protection against acquisition and carriage of encapsulated bacteria like Neisseria meningitidis serogroup C. Measurements of salivary antibodies as replacement for blood testing has important (cost-effective) advantages, particular in studies that assess the impact of large-scale vaccination or in populations in which blood sampling is difficult. This study aimed to estimate a threshold for meningococcal IgG salivary antibody levels to discriminate between unprotected and protected vaccinated individuals.MethodsMenA-, MenC-, MenW- and MenY-polysaccharide (PS) specific IgG levels in serum and saliva from participants in a meningococcal vaccination study were measured using the fluorescent-bead-based multiplex immunoassay. Functional antibody titers in serum against the four serogroups were measured with serum bactericidal assay using rabbit complement (rSBA). A threshold for salivary IgG was determined by analysis of ROC curves using a serum rSBA titer ≥128 as correlate of protection. The area under the curve (AUC) was calculated to quantify the accuracy of the salivary test and was considered adequate when ≥0.80. The optimal cut-off was considered adequate when salivary IgG cut-off levels provided specificity of ≥90%. True positive rate (sensitivity), positive predictive value, and negative predictive value were calculated to explore the possible use of salivary antibody levels as a surrogate of protection.ResultsThe best ROC curve (AUC of 0.95) was obtained for MenC, with an estimated minimum threshold of MenC-PS specific salivary IgG ≥3.54 ng/mL as surrogate of protection. An adequate AUC (> 0.80) was also observed for MenW and MenY with an estimated minimal threshold of 2.00 and 1.82 ng/mL, respectively. When applying these thresholds, all (100%) samples collected 1 month and 1 year after the (booster) meningococcal vaccination, that were defined as protective in the saliva test for MenC, MenW and MenY, corresponded with concomitant serum rSBA titer ≥128 for the respective meningococcal serogroups.ConclusionThe saliva test offers an alternative screening tool to monitor protective vaccine responses up to one year after meningococcal vaccination against MenC, MenW and MenY. Future (large) longitudinal vaccination studies evaluating also clinical protection against IMD or carriage acquisition are required to validate the currently proposed threshold in saliva.

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Section: Introductionmentioning

confidence: 99%

Use of saliva to monitor meningococcal vaccine responses: proposing a threshold in saliva as surrogate of protection

Ravenhorst

Klis

Rooijen

et al. 2019

BMC Med Res Methodol

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“… 3 IMD incidence is highest in infants, but a second smaller peak occurs in adolescents and young adults due to behavioral and lifestyle-associated risk factors. 4 , 5 …”

Section: Introductionmentioning

confidence: 99%

Four-year antibody persistence and response to a booster dose of a pentavalent MenABCWY vaccine administered to healthy adolescents and young adults

Sáez-Llorens

Beltrán-Rodríguez²,

Pizarro

et al. 2018

Human Vaccines & Immunotherapeutics

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This open-label, multicenter extension study (NCT02451514) assessed persistence of Neisseria meningitidis serogroups ABCWY antibodies 4 years after primary vaccination. Adolescents and young adults who previously received 2 doses of MenABCWY+OMV (Group III), 1 dose of MenACWY-CRM (Group VI), or newly-recruited vaccine-naïve participants (Group VII) were administered 1 (Group III) or 2 doses (Groups VI and VII) of MenABCWY+OMV, 1 month apart. Immunogenicity was assessed by human serum bactericidal assay (hSBA). Safety and reactogenicity were also evaluated. Percentages of participants with hSBA titers ≥8 (serogroups ACWY), ≥5 (serogroup B) and hSBA geometric mean titers (GMTs) were evaluated in all 129 enrolled participants (Group III: 33; Group VI: 46; Group VII: 50). Anti-ACWY antibody concentrations waned over 4 years post-vaccination, but remained above pre-vaccination concentrations. Similarly, levels of antibodies against serogroup B test strains also waned over 4 years post-vaccination, but remained above pre-vaccination concentrations for some strains. MenABCWY+OMV booster induced a robust anamnestic anti-ACWY response in Group III and VI and a good response against serogroup B test strains (≥82%) in Group III. In serogroup B-naïve participants (Groups VI and VII), anti-B responses to 2 doses of MenABCWY+OMV were less homogenous and lower than in Group III. MenABCWY+OMV was reactogenic, but well-tolerated. No safety concerns were identified. These findings indicate that although antibodies against N. meningitidis serogroups ABCWY waned over 4 years post-vaccination, exposure to a MenABCWY+OMV booster dose elicits an anamnestic response in adolescents previously exposed to the same or another multivalent meningococcal vaccine.

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“…This raises the question of the protective capacities of the infection induced antibodies in this group of patients including both young and old adults. It is likely that the immune response (antibody production) induced at the initial stage of infection, progresses too slowly to deal with the acute pneumococcal infection, similar to what is observed in meningococcal sepsis (Erlich & Congeni, 2012). The outcome of the pneumococcal infections will probably also depend on other host-specific immunological factors (Calbo & Garau, 2011).…”

Section: Discussionmentioning

confidence: 99%

Human antibody responses to pneumococcal surface protein A and capsular polysaccharides during acute and convalescent stages of invasive disease in adult patients

et al. 2013

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The IgG antibody responses to pneumococcal surface protein A (PspA) and capsular polysaccharides in acute and convalescent-phase sera from 10 adult patients with invasive pneumococcal disease were analysed. The relatedness between the strains were characterized by capsular serotyping (1, 4, 7F, 9V, 12F and 19F), multilocus sequence typing (MLST) and sequencing of the gene coding for PspA. Immunoblotting with the patient's own infecting strain used as whole cell antigen revealed strong antibody responses to PspA in 4 of 10 patients. Two of these patients showed cross reactivity of PspA antibodies within PspA families 1 and 2 by ELISA measurements with recombinant PspA proteins. Using ELISA, we found increased levels of capsular-specific antibodies during convalescent phase in 9 of 10 patients. All patients, except one, revealed low antibody levels in their acute phase sera. The binding of serum antibodies to live pneumococci using the patient's own infective strain was measured by flow cytometry. The antibodies binding to the live pneumococci corresponded to the serotype-specific polysaccharides by ELISA. Low antibody-binding activities to their infective strain in the acute serum may explain why they were not protected.

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Importance of circulating antibodies in protection against meningococcal disease

Cited by 17 publications

References 53 publications

Use of saliva to monitor meningococcal vaccine responses: proposing a threshold in saliva as surrogate of protection

Use of saliva to monitor meningococcal vaccine responses: proposing a threshold in saliva as surrogate of protection

Four-year antibody persistence and response to a booster dose of a pentavalent MenABCWY vaccine administered to healthy adolescents and young adults

Human antibody responses to pneumococcal surface protein A and capsular polysaccharides during acute and convalescent stages of invasive disease in adult patients

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