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[The bactericidal action of human neutrophils on meningococci in vitro]
A E Platonov1, I V Vershinina, H Käyhty
1Central Research Institute of Epidemiology, Moscow, Russia.
Abstract:
32 Russian patients with late complement component deficiency (LCCD) were immunize with tetravalent meningococcal polysaccharide vaccine (A + C + W135 + Y). Their immune response and infectious morbidity rate were followed for 6 years and the partial protective efficacy of vaccination was demonstrated. As the antibody-mediated complement-induced bactericidal activity of plasma was completely absent in persons with LCCD, the bactericidal action of human neutrophils on meningococci of groups A, W135 and B was studied under the conditions of incubation with serum samples collected from persons with LCCD before and after vaccination. In LCCD serum alone the exponential growth of meningococci was observed, while the addition of human neutrophils resulted in the essential inhibition of the growth of meningococci (up to their complete elimination). The proportion of serum samples stimulating the elimination of group A and W 135 meningococci by neutrophils was almost 40% of the serum samples collected before vaccination and significantly increased among the serum samples collected after vaccination (up to 84%) or revaccination (up to 90%). At the same time the capacity of an individual serum sample to promote the bactericidal effect of neutrophils against meningococci correlated with its content of specific anti-polysaccharide IgG and IgM antibodies, as well as antibodies to the inner core of lipopolysaccharide. The interaction of neutrophils with meningococci was significantly inhibited after incubation in heat-inactivated serum, suggesting that this interaction was partly mediated along the following path: the binding of IgM and IgG antibodies with bacteria--the activation of complement and the deposition of C3 complement on bacteria--the binding of meningococci with CR3 receptors of neutrophils.
Insights
Late complement component deficiency (LCCD) patients showed improved meningococcal defense after vaccination. Neutrophils, aided by vaccine-induced antibodies, effectively eliminated bacteria, demonstrating partial vaccine efficacy in these vulnerable individuals.
Area of Science:
- Immunology
- Microbiology
- Vaccinology
Background:
- Late complement component deficiency (LCCD) impairs antibody-mediated bacterial clearance.
- Meningococcal infections pose a significant risk to individuals with LCCD.
- The role of neutrophils in combating meningococci in LCCD patients is not fully understood.
Purpose of the Study:
- To evaluate the immune response and infectious morbidity in LCCD patients vaccinated with a tetravalent meningococcal polysaccharide vaccine.
- To investigate the bactericidal activity of neutrophils against meningococci using serum from LCCD patients before and after vaccination.
- To elucidate the mechanisms underlying neutrophil-mediated bacterial killing in LCCD.
Main Methods:
- 32 Russian patients with LCCD were vaccinated with a tetravalent meningococcal polysaccharide vaccine (A+C+W135+Y).
- Immune response and infectious morbidity were monitored for 6 years.
- Neutrophil bactericidal activity against different meningococcal groups was assessed using patient serum, with and without heat inactivation.
Main Results:
- Vaccination demonstrated partial protective efficacy in LCCD patients.
- Neutrophils significantly inhibited meningococcal growth, up to complete elimination, when incubated with LCCD patient serum.
- The proportion of serum samples promoting neutrophil-mediated killing increased significantly post-vaccination (from ~40% to 84%) and revaccination (to 90%).
- This enhanced bactericidal capacity correlated with specific IgG and IgM antibody levels and was partly complement-dependent.
Conclusions:
- Meningococcal polysaccharide vaccination enhances neutrophil-mediated bactericidal activity in LCCD patients.
- Vaccine-induced antibodies, complement activation, and neutrophil CR3 receptor interactions are crucial for this defense mechanism.
- Neutrophil function, supported by vaccination, offers partial protection against meningococcal disease in LCCD individuals.