A Noncovalent Complex Vaccine Prepared with Detoxified Escherichia coli J5 (Rc Chemotype) Lipopolysaccharide and Neisseria meningitidis Group B Outer Membrane Protein Produces Protective Antibodies against Gram-Negative Bacteremia

Abstract

Earlier studies showed that purified IgG from sera of rabbits immunized with a boiled Escherichia coli J5 (Rc chemotype) whole cell vaccine protected neutropenic rats against gram-negative bacterial sepsis. In the present study, de-O-acylated J5 lipopolysaccharide (J5 DLPS) as a noncovalent complex with Neisseria meningitidis group B outer membrane protein (GBOMP) elicited anti-J5 LPS antibodies in rabbits. IgG prepared from immune rabbit sera protected neutropenic rats against lethal challenge with Pseudomonas aeruginosa 12:4:4 (Fisher Devlin immunotype 6). Sixteen of 26 rats treated with the postimmune serum IgG were protected compared with none of 20 rats treated with the control rabbit serum IgG (P < .001). In vitro binding studies showed binding of anti-J5 IgG to several gram-negative bacteria. These results indicate that a subunit vaccine made of J5 DLPS as a noncovalent complex with GBOMP may protect against gram-negative bacteremia.

Release of Gram‐Negative Outer‐Membrane Proteins into Human Serum and Septic Rat Blood and Their Interactions with Immunoglobulin in Antiserum toEscherichia coliJ5

“…In addition, it has been difficult to directly demonstrate substantial increased binding to LPS from heterologous gram-negative bacteria by the immunoglobulins in polyclonal antiserum to E. coli J5 [7,8]. Perhaps the strongest evidence that anti-LPS antibody might be involved comes from experiments in which passive immunization with immunoglobulin directed against a vaccine consisting of deacylated E. coli J5 LPS protected in a neutropenic model of sepsis [20]. Nonetheless, although antisera raised to heat-killed rough strains have been reported to protect, the exact mechanism by which this protection occurs remains elusive [21].…”

Review: Evidence against the hypothesis that antibodies to the inner core of lipopolysaccharides in antisera raised by immunization with enterobacterial deep-rough mutants confer broad-spectrum protection during Gram-negative bacterial sepsis

“…However, the increments in binding were highly variable; almost half of the bacterial strains exhibited negligible increments in binding and inexplicably, the J5 IgG fraction bound to 11.6% of viable J5 organisms, in contrast to 44.3% of the P. aeruginosa serotype 6 challenge strain. 155 Davis et al reported that J5 rabbit antiserum was capable of binding to LPS from group A, B, and C meningococci, as assessed by an HA assay.Z8 Meningococcal (as well as other neisserial) LPS do not possess 0 polysaccharide side chains. Rather, they are comparable to the unencumbered R-form LPS in rough-mutant enterobacteria and possess both group-specific and more broadly reactive epitopes.…”

Lipopolysaccharide Modifications of a Cholera Vaccine Candidate Based on Outer Membrane Vesicles Reduce Endotoxicity and Reveal the Major Protective Antigen

“…However, an ideal vaccine candidate should not be limited to these immunization routes. Moreover, a general reduction of endotoxicity to minimize adverse effects might be necessary for a safe application of the OMV vaccine candidate in humans, as highlighted by a variety of other vaccine candidates containing LPS (47)(48)(49)(50)(51)(52)(53)(54)(55). For example, the Neisseria meningitidis OMV vaccines, used to control outbreaks in Scandinavia and New Zealand, include an additional step to remove most of the LPS by detergent extraction (56,57).…”