Killing of Meningococci by Neutrophils: Effect of Vaccination on Patients with Complement Deficiency

Abstract

To evaluate the in vitro effect of meningococcal vaccination, 3 C7-deficient (C7-D) siblings and 2 normal controls were studied before and 6 weeks after vaccination with treatment meningococcal vaccine (serogroups A, C, Y, and W). Serobactericidal activity was not detected in the C7-D subjects and was low in the controls. Neither group was affected by vaccination. However, opsonized phagocytic killing increased significantly following vaccination in C7-D subjects and normal controls, despite only a modest increase in antimeningococcal titers. Heat inactivation of sera added to neutrophils resulted in low killing activity, which did not increase after vaccination. Thus, tetravalent meningococcal vaccine appears to enhance the phagocytic killing of meningococci in both normal and C7-deficient persons and should be given to all persons with C7 deficiencies.

Protection against meningococcal serogroup ACYW disease in complement-deficient individuals vaccinated with the tetravalent meningococcal capsular polysaccharide vaccine

“…We found that phagocytic killing of serogroups A and W135 was enhanced in post-vaccination sera from nine (47%) of the 20 LCCD persons. The results of two earlier studies demonstrated an efficient phagocytic killing of meningococci opsonized with serum from LCCD patients [19,29]. We found that anticapsular IgG antibody levels and opsonophagocytic activity did not coincide.…”

“…Protection against meningococcal disease in persons with LCCD is only due to antibody-mediated opsonophagocytic killing [3,19,29]. If PMN require late complement components for phagocytic killing, vaccination is not useful in LCCD individuals.…”

Vaccination of patients deficient in a late complement component with tetravalent meningococcal capsular polysaccharide vaccine

“…If the late complement components are important in phagocytic killing of meningococci, the vaccination is not useful for LCCD patients. The studies of Andreoni et al [6] and Schlesinger et al [24) speak against ihis, as meningococci opsonized in an LCCD serum could be efficiently killed in an in vitro phagocytosis assay. Furthermore, vaccination with the tetravalent meningococcal vaccine enhanced the phagocytic killing significantly.…”

Vaccination against encapsulated bacteria in hereditary C2 deficiency results in antibody response and opsonization due to antibody-dependent complement activation

“…For instance, favorable in vitro responses to tetravalent meningococcal vaccination have been demonstrated in properdin deficiency and in late-complement component deficiencies [10,11,12]. Vaccination of C2D patients has been considered to be advisable despite a lack of supportive data [2,13].…”