Meningococcal lipopolysaccharide (LPS)-derived oligosaccharide-protein conjugates evoke outer membrane protein- but not LPS-specific bactericidal antibodies in mice: influence of adjuvants

Abstract

Meningococcal lipopolysaccharide (LPS)-derived oligosaccharides (OS) were coupled to tetanus toxoid (TT) and purified P1.7,16 outer membrane proteins (OMP). The immunogenicities of the conjugates with and without the addition of the adjuvant Quil A or the nonionic block polymer L121 were studied in mice. Immunotype L2 and L3,7,9 OS-TT conjugates induced immunoglobulin G (IgG) responses that were strongly augmented by Quil A and L121. These adjuvants not only enhanced the amount of IgG evoked but also shifted the IgG subclass distribution from mainly IgGl toward the complement-activating subclasses IgG2a and IgG2b. The antibodies induced were directed against the OS part of meningococcal LPS. They were not bactericidal for group B meningococci. Both the L3,7,9 OS-P1.7,16 OMP conjugate and purified P1.7,16 OMP evoked a strong IgG response against the P1.7,16 OMP but not against the L3,7,9 LPS. These anti-OMP IgG responses were comparable to the IgG OMP-specific responses induced by the H44/76 or HIII-5 outer membrane vesicles but still did not lyse group B meningococcal strains. The IgG response evoked with OS-OMP or purified OMP consisted mainly of the IgGl subclass, whereas the H44/76 or HIII-5 outer membrane vesicles induced high amounts of bactericidal IgG2a and IgG2b antibodies next to the IgGl antibodies. The addition of the adjuvant Quil A or L121 to OS-OMP or OMP resulted in the induction of high levels of bactericidal anti-Pl.7,16-specific OMP antibodies, as reflected by the presence of substantial amounts of IgG2a and IgG2b antibodies. These results indicate that (i) mouse anti-LPS antibodies evoked by LPS-derived OS-protein conjugates are not bactericidal for group B meningococci, (ii) extensive purification of P1.7,16 OMP can lead to the loss of the intrinsic adjuvant properties of outer membrane vesicle preparations, and (iii) the addition of suitable adjuvants restores the ability of these purified P1.7,16 OMP to induce

MARCO, an innate activation marker of macrophages, is a class A scavenger receptor for Neisseria meningitidis

“…NM, a gram‐negative diplococcus, is an important cause of bacterial meningitis and septic shock in humans. The organism and its cell wall derivatives are potent immune adjuvants 16, able to stimulate pro‐inflammatory cytokine secretion and Ab production, and to activate complement 17. Generally, the humoral system plays a major role in anti‐neisserial immunity, but non‐opsonic phagocytosis in the opsonin‐poor nasopharynx and meninges, two entry points for NM, may play an important role in local resistance to infection 18, 19.…”

Neisseria meningitidis serogroup B: laboratory correlates of protection

“…N. meningitidis expresses a number of di¡erent glycoforms of LPS and the expression di¡ers in invasive versus carriage isolates. No clinical data are yet available, but preclinical data show the induction of opsonic rather than bactericidal antibodies by detoxi¢ed LPS or LPS conjugate vaccines [18]. Recent publication of the genomes of two meningococcal isolates o¡ers new opportunities for the identi¢cation of candidate antigens like autotransporters, adhesins and lipoproteins which can possibly act as new vaccine components.…”

Porins and lipopolysaccharide from Salmonella typhimurium regulate the expression of CD80 and CD86 molecules on B cells and macrophages but not CD28 and CD152 on T cells

“…Some outer membrane proteins of Gram‐negative bacteria act as porins and have an important role both in bacterial cell physiology and interaction with the host [8–11]. Porins are present in the outer membrane of Gram‐negative bacteria as integral membrane proteins and are released together with the lipopolysaccharide (LPS) during cell growth by a mechanism known as blebbing [12] or by bacterial lysis [13].…”

“…Porins perfom several biological functions on inflammatory and immunological cell response [10,11,14–16]. The protective role of the outer membrane protein antibodies, among which are porins from Salmonella [17], Neisseria [18,19], Haemophilus [20] and Vibrio [21], has been previously demonstrated.…”