Gonococcal pilus vaccine. Studies of antigenicity and inhibition of attachment.

Abstract

A B S T R A C T A gonococcal pilus vaccine or placebo was injected subcutaneously or intramuscularly into 71 human volunteers. The vaccine was found to be safe. The principal adverse reaction was a complaint ofa sore arm, which was caused, at least in part, to the volume of material injected. 6 of 64 (9%) volunteers receiving the larger doses also complained of malaise. The vaccine was found to be antigenic. All of the volunteers developed an immunoglobulin class-specific antibody response as measured by a solid phase radioimmunoassay. The antibody was capable of blocking the attachment of gonococci to epithelial cells. A slight antibody response was also demonstrated to gonococcal lipopolysaccharide but the antibody responsible for blocking attachment of gonococci was directed entirely at the pilus protein. The stimulated antibodies were shown to crossreact with isolated pili of heterologous gonococcal strains and to block the attachment of heterologous gonococci. Absorption of immune sera by a heterologous pilus reduced the inhibition of attachment antibodies to the pre-immune level, suggesting that the immune response was directed at a common pilus determinant.

Genetic, Structural, and Antigenic Analyses of Glycan Diversity in the O-Linked Protein Glycosylation Systems of HumanNeisseriaSpecies

“…First, a large number of studies in the 1960s to 1990s examined the immunogenicity and antigenicity of N. gonorrhoeae pili in order to assess their potential as a gonococcal vaccine component (8,30,42,60). Together with analogous studies of N. meningitidis pili, these studies provided serological evidence for pilus antigenic diversity, which was subsequently interpreted as a reflection of wholesale changes in pilin primary structure resulting from gene conversion-like events involving multiple pilin gene copies (55,74).…”

Specificity of antibodies against Neisseria gonorrhoeae that stimulate neutrophil chemotaxis. Role of antibodies directed against lipooligosaccharides.

“…Nevertheless rapid and efficient complement-dependent serum-bactericidal activity and neutrophil accumulation are components ofthe host response to N. gonorrhoeae that may be important in preventing DGI. The combination of antibodies measured in female genital secretions directed against specific gonococcal antigens, such as LOS (50), and the presence ofcomplement suggest a mode ofperpetuating inflammation that may result in a PMN leukocyte response accompanied by symptomatic local disease. Our data indicate a role for antibody in determining the pattern of neutrophil chemotaxis stimulated by serum-sensitive and resistant gonococci in a manner analogous to its role in complement dependent killing of gonococci.…”

“…gonorrhoeae are responsible for complement-dependent bactericidal activity (12,14,50,51). This activity has been ascribed to LOS antibodies ofthe IgM class in NHS, directed against serum-sensitive strains (12,(52)(53) or in the case ofimmune DGI serum, IgG antibodies against serum resistant LOSs that kill these strains (14,54).…”

Mucosal Immunity and Evasion Strategies of Neisseria gonorrhoeae

“…In fact, women with these antibodies were at increased risk to gonococcal infection (Plummer et al, 1993). The absence of induction of humoral response results on limited or no protection against re-infection with N. gonorrhoeae despite the generation of serum antibody responses against antigens produced by several prototype gonococcal vaccines (Boslego et al, 1991;McChesney et al, 1982;Tramont et al, 1981). (Kohl et al, 1992) Porin Up-regulated B7-2 expression of B lymphocytes (Wetzler et al, 1996) Heat labile and fixed N. gonorrhoeae IgG>IgA>IgM serum (Cohen, 1967) Pili and outer membrane protein II IgG serum (Lammel et al, 1985) Outer membrane protein II IgA serum (Lammel et al, 1985) Outer membrane protein I and II and pili IgG and IgA vaginal fluid (Lammel et al, 1985) LPS IgG>IgA in serum (Ison et al, 1986) Outer membrane protein III IgG in serum (Rice et al, 1986) N. gonorrhoeae MS11 Slight increase of IgG and IgA in serum (Hedges et al, 1999) …”