Trivalent native outer membrane vesicles (nOMVs) derived from three genetically modified Neisseria meningitidis serogroup B strains have been previously evaluated immunologically in mice and rabbits. This nOMV vaccine elicited serum bactericidal activity (SBA) against multiple N. meningitidis serogroup B strains as well as strains from serogroups C, Y, W, and X. In this study, we used trivalent nOMVs isolated from the same vaccine strains and evaluated their immunogenicity in an infant Rhesus macaque (IRM) model whose immune responses to the vaccine are likely to be more predictive of the responses in human infants. IRMs were immunized with trivalent nOMV vaccines and sera were evaluated for exogenous human serum complement-dependent SBA (hSBA). Antibody responses to selected hSBA generating antigens contained within the trivalent nOMVs were also measured and we found that antibody titers against factor H binding protein variant 2 (fHbpv2) were very low in the sera from animals immunized with these original nOMV vaccines. To increase the fHbp content in the nOMVs, the vaccine strains were further genetically altered by addition of another fHbp gene copy into the porB locus. Trivalent nOMVs from the three new vaccine strains had higher fHbp antigen levels and generated higher anti-fHbp antibody responses in immunized mice and IRMs. As expected, fHbp insertion into the porB locus resulted in no PorB expression. Interestingly, higher expression of PorA, an hSBA generating antigen, was observed for all three modified vaccine strains. Compared to the trivalent nOMVs from the original strains, higher PorA levels in the improved nOMVs resulted in higher anti-PorA antibody responses in mice and IRMs. In addition, hSBA titers against other strains with PorA as the only hSBA antigen in common with the vaccine strains also increased.
Abstract. The pathogenicity of the A4557-5 strain of infectious laryngotracheitis virus for eight-week-old chickens was investigated by aerosol route of infection; chickens were necropsied five days after infection. The virus caused mild catarrhal tracheitis, peribronchial lymphoid infiltration, and focal lymphocytic infiltration in the lung and focal lymphocytic infiltration in the air sacs of some chickens. Chickens infected with this virus developed low levels of humoral antibody and were resistant to intratracheal challenge with the virulent V154 strain. By comparison, aerosol infection with a similar dose of virulent V154 strain caused severe necrotizing laryngotracheitis with marked suppurative bronchopneumonia and airsacculitis.The respiratory disease of infectious laryngotracheitis in chickens usually is recognized as a severe, necrotizing laryngitis and tracheitis with catarrhal exudate, hemorrhage, and formation of a diphtheritic membrane in the lumen of the trachea, as well as sinusitis, bronchopneumonia, and airsacculitis 11, 7-9, 14, 151. With subacute strains of the virus, necrosis of respiratory tract epithelium is less severe and catarrhal tracheitis occurs with regenerative hyperplasia in the trachea and lungs Mild clinical disease has been reported following laboratory attenuation of the virus [5] and also with natural disease [12, 131 but has not been documented previously by descriptions of the gross and microscopic lesions. These studies were undertaken to characterize the pathogenicity of the A4557-5 strain of infectious laryngotracheitis virus which was isolated from chickens during a field outbreak of mild respiratory disease. The aerosol route of experimental infection was used to ensure virus infection of the lower respiratory tract in order to describe the lesions in various sites of the respiratory tract including turbinates, larynx, trachea, lungs, and air sacs.The V154 strain of infectious laryngotracheitis virus is a reference virulent virus strain causing necrotizing laryngotracheitis when administered by intratracheal inoculation. Because of the extremely low pathogenicity of A4557-5 virus in preliminary studies by intratracheal inoculation, the aerosol infection with A4557-5 strain was [lo].
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