Naturally acquired passive protective activity against Neisseria meningitidis Group C in the absence of serum bactericidal activity.

نویسندگان

  • Jo Anne Welsch
  • Dan Granoff
چکیده

The hallmark of immunity to meningococcal disease is a bactericidal titer in serum of > or =1:4 measured with human complement, but this threshold titer may underestimate the extent of protection. We used the infant rat model of meningococcal bacteremia to measure group C passive protective activity in serum samples from 91 unimmunized adults living in California. A total of 35 sera (38.5%) had passive protective activity. Sera with complement-mediated bactericidal titers of > or =1:4 were 3.4-fold more likely to confer protection (89%) than nonbactericidal sera (26%; P < 0.0001). Thus, bactericidal titers of > or =1:4 are a marker of protection, but this threshold lacks sensitivity for predicting protective activity. We investigated the 73 sera with bactericidal titers of <1:4 to determine the basis of protective activity. The 19 sera with protective activity had a higher geometric mean group C anticapsular antibody concentration (0.72 microg/ml) than the 54 sera that lacked protective activity (0.16 microg/ml; P < 0.001). Thus, protective activity in the absence of bactericidal activity was associated with higher concentrations of anticapsular antibodies, but not all sera with anticapsular antibodies conferred protection. Of 18 nonbactericidal sera with anticapsular antibody concentrations between 0.31 and 0.99 microg/ml, the 11 sera that conferred protection had a higher mean antibody avidity constant (21.9 nM(-1)) than the 7 nonprotective sera (14.6 nM(-1); P < 0.03). Thus, in sera with titers of <1:4, protective activity is associated with higher-avidity group C anticapsular antibodies, which are present in concentrations insufficient to elicit complement-mediated bacteriolysis in vitro but sufficient to confer protection in an in vivo bacteremia model.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Construction and assessment of the immunogenicity and bactericidal activity of fusion protein porin A from Neisseria meningitidis serogroups A and B admixed with OMV adjuvant as a novel vaccine candidate

Objective(s): The porins A and B and also outer membrane vesicles (OMVs) of Neisseria meningitidis are used for vaccine purposes. In the present study, we aimed to design a new vaccine candidate based on a fusion of PorA of serogroups A and B of N. meningitidis admixed with OMV and evaluate it in an animal model.Materials and Methods: Af...

متن کامل

Evidence for naturally acquired T cell-mediated mucosal immunity to Neisseria meningitidis.

Naturally acquired protective immunity against Neisseria meningitidis is thought to partially explain the disparity between the high levels of carriage in the human nasopharynx and the rare incidence of disease. To investigate this immunity to Neisseria meningitidis at the mucosal level, in vitro cellular responses to outer membrane vesicle preparations derived from this pathogen were examined ...

متن کامل

Immunity to Neisseria meningitidis group B in adults despite lack of serum bactericidal antibody.

Serum-complement-mediated bactericidal antibody (SBA) remains the serologic hallmark of protection against meningococcal disease, despite experimental and epidemiologic data that SBA may underestimate immunity. We measured bactericidal activity against three strains of Neisseria meningitidis group B in sera from 48 healthy adults and in whole blood from 15 subjects. Blood was anticoagulated wit...

متن کامل

Ex vivo model of meningococcal bacteremia using human blood for measuring vaccine-induced serum passive protective activity.

The binding of complement factor H (fH) to meningococci was recently found to be specific for human fH. Therefore, passive protective antibody activity measured in animal models of meningococcal bacteremia may overestimate protection in humans, since in the absence of bound fH, complement activation is not downregulated. We developed an ex vivo model of meningococcal bacteremia using nonimmune ...

متن کامل

Antibody to genome-derived neisserial antigen 2132, a Neisseria meningitidis candidate vaccine, confers protection against bacteremia in the absence of complement-mediated bactericidal activity.

Genome-derived neisserial antigen 2132 (GNA2132) is a novel vaccine candidate that was identified during the Neisseria meningitidis group B strain MC58 genome-sequencing project. To assess the vaccine potential of GNA2132, we prepared antisera from mice immunized with recombinant GNA2132 (gene from strain NZ394/98). Anti-GNA2132 antibody bound to the surface of live bacteria from all 7 capsular...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Infection and immunity

دوره 72 10  شماره 

صفحات  -

تاریخ انتشار 2004