Cross-reactivity of antibodies against PorA after vaccination with a meningococcal B outer membrane vesicle vaccine.

The cross-reactivity of PorA-specific antibodies induced by a monovalent P1.7-2,4 (MonoMen) and/or a hexavalent (HexaMen) meningococcal B outer membrane vesicle vaccine (OMV) in toddlers and school children was studied by serum bactericidal assays (SBA). First, isogenic vaccine strains and PorA-identical patient isolates were compared as a target in SBA, to ensure that the vaccine strains are representative for patient isolates. Geometric mean titers (GMTs) in SBA against patient isolates with subtypes P1.5-2,10 and P1.5-1,2-2 after vaccination with HexaMen were generally lower than those against vaccine strains with the same subtype, although the percentage of vaccine responders (> or =4-fold increase in SBA after vaccination) was not affected. Using various P1.7-2,4 patient isolates, GMTs as well as the number of vaccine responders were higher than for the P1.7-2,4 vaccine strain, indicating that the use of the P1.7-2,4 vaccine strain may have underestimated the immunogenicity of this subtype in HexaMen. Secondly, the cross-reactivity of antibodies induced by MonoMen and HexaMen was studied using several patient isolates that differed from the vaccine subtypes by having minor antigenic variants of one variable region (VR), by having a completely different VR or by having a different combination of VRs. MonoMen induced P1.4-specific antibodies that were cross-reactive with P1.4 variants P1.4-1 and P1.4-3. HexaMen induced a broader cross-reactive antibody response against various patient isolates with one VR identical to a vaccine subtype or a combination of VRs included in HexaMen. Cross-reactivity, measured by a fourfold increase in SBA after vaccination, against these strains ranged from 23 to 92% depending on the subtype of the tested strain and was directed against both VR1 and VR2. The extended cross-reactivity of vaccinee sera induced by HexaMen against antigenic variants has important favorable implications for meningococcal B OMV vaccine coverage.

Movement of the endotracheal tube during laparoscopic hernia repair.

BACKGROUND: Laparoscopic surgery is not without its problems, and one of the less known is cephalad displacement of the carina and relative movement of the endotracheal tube in the trachea. The aetiology of this is presumably a consequence of both pneumoperitoneum and the Trendelenburg position frequently adopted during laparoscopic surgery. METHOD: We studied 30 patients undergoing laparoscopic hernia repair utilising 10 degrees of Trendelenburg position and an intra-abdominal inflation pressure of between 12 and 15 mm Hg (mean 13.6 mm Hg). We measured the distance between the tip of the endotracheal tube and the carina using a fibreoptic bronchoscope. RESULT: This distance decreased only slightly, from a mean (SD) of 39.6 (13) mm after intubation, to 38.9 (12.6) mm after adoption of Trendelenburg tilt and pneumoperitoneum. This did not represent a statistically significant change (P=0.09). CONCLUSION: We conclude that the endotracheal tube does not routinely migrate towards the carina when laparoscopic hernia repair is performed under these conditions.

Phase I clinical trial with a hexavalent PorA containing meningococcal outer membrane vesicle vaccine.

A meningococcal outer membrane vesicle (OMV) vaccine was prepared from two production strains designed to express three serosubtype-specific class 1 outer membrane proteins or PorA. The resulting hexavalent PorA OMV vaccine contained the serosubtypes P1.7,16; P1.5,2; P1.19,15; P1.7h,4; P1.5c,10; P1.12,13 and were used to immunize adult volunteers. A single immunization with two dosages, 7.5 and 15 micrograms of the individual PorAs, was studied. The vaccine was considered safe for further use. Approximately half of the volunteers demonstrated a fourfold increase in bactericidal antibody activity against six test strains expressing the specific PorAs when given the higher dosage. This bactericidal activity was found to be directed against PorA.

Development, characterization, and biological properties of meningococcal immunotype L3,7,(8),9-specific monoclonal antibodies.

In this study, we characterize the properties of nine monoclonal antibodies (MAbs) that recognize meningococcal lipopolysaccharides (LPS). The following three specific MAbs that had not been described previously were elicited in BALB/c mice by using an immunotype L3,7,9 oligosaccharide-tetanus toxoid conjugate in combination with Quil A: 4D1-B3, 3A12-E1, and 4A8-B2. These MAbs reacted with L3,7,9 LPS on immunoblots and in the LPS enzyme-linked immunosorbent assay (ELISA) and recognised strains containing L3, L3,7, L8 (except 3A12-E1), or L9 LPS in the whole-cell ELISA. The six other MAbs have been described in previous studies (K. Saukkonen, M. Leinonen, H. Abdillahi, and J.T. Poolman, Vaccine 7:325-328, 1989; R.J.P.M. Scholten, B. Kuipers, H.A. Valkenburg, J. Danjert, W.D. Zollinger, and J.T. Poolman, J. Med. Microbiol., in press) and were obtained after immunization with outer membrane protein complexes containing LPS: MN15A11, MN15A8-1, MN15A17-1, MN11A11G, MN14F20-11, and MN14F21-11. MN15A11 was specific for L3,7,9 LPS and displayed properties similar to those of 3A12-E1. MN15A17-1, MN14F20-1, and MN11A11G were cross-reactive, and MN14F21-11 was specific for the L1,8 immunotype. Epitope specificities of MAbs reacting with L3,7,(8),9 strains were analyzed. MAbs 4D1-B3, 3A12-E1, and 4A8-B2 recognized phosphoethanolamine group-containing oligosaccharide-specific epitopes. MN15A11 and MN15A17-1 were probably directed against a conformational epitope, although for MN5A11 recognition of an unknown L3,7,9-specific epitope in the 2-keto-3-deoxyoctulosonic acid (KDO)-lipid A region cannot be excluded. MN15A8-1, a strongly cross-reactive MAb, recognized a determinant which included the KDO-lipid A region and the more terminal saccharides.(ABSTRACT TRUNCATED AT 250 WORDS)

Measurement of O6-ethyldeoxyguanosine and N-(deoxyguanosin-8-yl)-N-acetyl-2-aminofluorene in DNA by high-sensitive enzyme immunoassays.

Antibodies raised in rabbits against the bovine serum albumin conjugates of O6-ethylguanosine and N-(guanosin-8-yl)-N-acetyl-2-aminofluorene have been used to develop a high-sensitive enzyme-linked immunosorbent assay (HS-ELISA) for the quantification of adducts in DNA modified by ethylating agents and N-acetyl-2-aminofluorene. Linear dose-response relations were obtained in the non-competitive HS-ELISA between 0.5 fmol and 50 fmol O6-ethyldeoxy-guanosine per 2.8 microgram DNA, and between 0.1 fmol and 20 fmol N-(deoxyguanosin-8-yl)-N-acetyl-2-aminofluorene per 0.8 microgram DNA. The sensitivity of an ultrasensitive radioimmunoassay was in the same order of magnitude. Modification levels as low as 0.1 mumol of adduct/mol DNA-nucleotides (1: 10(7)) can be detected by each assay.