Immunogenicity of Intranasally Administered Meningococcal Native Outer Membrane Vesicles in Mice

Abstract

Colonization of the human nasopharyngeal region by Neisseria meningitidis is believed to lead to natural immunity. Although the presence of bactericidal antibody in serum has been correlated with immunity to meningococcal disease, mucosal immunity at the portal of entry may also play an important role. This study was undertaken to examine in mice the possibility of safely using native outer membrane vesicles (NOMV) not exposed to detergent as an intranasal (i.n.) vaccine. The mucosal and systemic responses of mice to intranasal and intraperitoneal (i.p.) vaccination with NOMV were compared over a range of doses from 0.1 to 20 μg. Intranasal vaccination of mice with NOMV induced a strong systemic bactericidal antibody response, as well as a strong local immunoglobulin A immune response in the lung as determined by assay of lung lavage fluid by enzyme-linked immunosorbent assay and lung antibody secreting cells by enzyme-linked immunospot assay. However, 8- to 10-fold-higher doses of NOMV were required i.n. compared to i.p. to elicit an equivalent bactericidal antibody response in serum. Some NOMV vaccine was aspirated into the lungs of mice during i.n. immunization and resulted in an acute inflammatory response that peaked at 1 to 2 days postimmunization and was cleared by day 7. These results indicate that i.n. delivery of meningococcal NOMV in mice is highly effective in eliciting the production of both a mucosal immune response and a systemic bactericidal antibody response.

Bacterial membrane vesicles deliver peptidoglycan to NOD1 in epithelial cells

“…In contrast, NOD1 KO mice did not produce any Cxcl2 mRNA responses, nor any OMV‐specific IgG antibodies, in response to oral administration of H. pylori OMVs. These findings provide an immunological basis for the known efficacy of OMV‐based vaccines, such as the one developed against the NOD1‐signalling pathogen, N. meningitidis (Saunders et al. , 1999; Antignac et al.…”

Evaluation of the immune response induced by a nasal anthrax vaccine based on the protective antigen protein in anaesthetized and non-anaesthetized mice

“…It was previously considered to be advantageous to have a vaccine reach the lung to achieve a total respiratory immunization in man (Yetter et al 1980;el Guink et al 1989;de Haan et al 1995). However, deeply inhaled vaccine may lead to severe pulmonary inflammation (Szarka et al 1997;Saunders et al 1999;Simecka et al 2000).…”

Outer membrane vesicles as platform vaccine technology

“…The detergent D‐OMVs, are extracted from cells with detergent which also reduces the content of reactogenic LPS. The term native N‐OMV is used for intact spontaneous OMVs from cell supernatant [40], as well as for OMVs that are generated from concentrated dead cells with non‐detergent cell disruption techniques [90, 112]. Here, native N‐OMV will be used for vesicles extracted from cells with detergent–free methods, in accordance with previous nomenclature, and to be able to clearly distinguish them from the wild‐type spontaneous OMVs and the detergent‐extracted OMVs.…”

“…As mild chemical alternative to detergents EDTA [94, 163] has been tested, and sonication as a mechanical vesicle releasing technique [167] and vortexing [168] has been used to prepare an N‐OMV fraction. For Neisseria a combination of detergent‐free techniques [112, 130] has been performed to obtain N‐OMVs.…”