Biomedical subjects

A Aase

Publications and source records attributed to A Aase.

At least 19 recordsLinked to original sources

PubMed2004

The four mouse IgG isotypes differ extensively in bactericidal and opsonophagocytic activity when reacting with the P1.16 epitope on the outer membrane PorA protein of Neisseria meningitidis.

Mouse monoclonal antibodies (MoAbs) of the four IgG isotypes, all specific for the P1.16 epitope on the meningcoccal PorA protein, were tested for functional activities. The avidities of the antibodies, measured by NH4SCN elution in enzyme-linked immunosorbent assay, showed similar values for all the MoAbs. The serum bactericidal activity (SBA) defined as the lowest concentration of antibodies giving 50% reduction in the number of meningococcal colony-forming units using human serum as complement, showed a hierarchy of IgG3 >> IgG2b > IgG2a >> IgG1. For the opsonophagocytosis (OP), the hierarchy was IgG3 > IgG2b = IgG2a >> IgG1. OP was measured in flow cytometry using log-phase live meningococci as target cells, normal human peripheral blood polymorphonuclear cells (PMNs) as effector cells and human serum as a complement source. The mouse MoAbs were negative in OP when using human PMNs in the absence of complement. The results demonstrate the importance of choosing the right isotype of mouse MoAbs when using them to judge the potential vaccine importance of their corresponding antigen. If such MoAbs should be used for passive vaccination against infectious diseases, the isotype would presumably play an important role for their anticipated clinical effects.

Animals↗

PubMed2003

Comparison of functional immune responses in humans after intranasal and intramuscular immunisations with outer membrane vesicle vaccines against group B meningococcal disease.

A serogroup B meningococcal outer membrane vesicle (OMV) vaccine was delivered either intranasally or intramuscularly to 12 and 10 volunteers, respectively. The mucosal vaccine was given as four weekly doses followed by a fifth dose after 5 months; each dose consisted of OMVs equivalent to 250 microg of protein. The intramuscular (i.m.) vaccine, consisting of the same OMVs but adsorbed to Al(OH)(3), was administered as three doses each of 25 microg of protein, with 6 weeks interval between first and second doses and the third dose after 10 months. Both groups of vaccinees demonstrated significant immune responses when measured as specific IgG antibodies against live meningococci, as serum bactericidal activity (SBA) and as opsonophagocytic activity. Two weeks after the last dose, the anti-meningococcal IgG concentrations were significantly higher in the i.m. group (median IgG concentration: 43.1 microg/ml) than in the intranasal group (10.6 microg/ml) (P=0.001). The corresponding opsonophagocytic activity was 7.0 and 3.0 (median log(2) titre) (P=0.001), and the SBA was 5.0 and 2.0 (median log(2) titre) (P=0.005), for the i.m. and intranasal groups, respectively. The last immunisation induced an enhanced immune response in the i.m. group, whereas the intranasal group showed no significant booster response. Accordingly, affinity maturation of anti-OMV-specific IgG antibodies was seen only after i.m. vaccination. The IgG1 subclass dominated the responses in both groups, whereas the significant IgG3 responses observed in the i.m. group were absent in the intranasal group. Although the intranasal OMV vaccination schedule used here induced functional immune responses relevant to protection, an improved vaccine formulation and/or a modified mucosal immunisation regimen may be needed to achieve a systemic effect comparable to that seen after three doses of intramuscular vaccination.

Administration, Intranasal↗

PubMed2003

Binding properties and anti-bacterial activities of V-region identical, human IgG and IgM antibodies, against group B Neisseria meningitidis.

We have constructed chimaeric (ch) mouse/human antibodies with identical binding regions isolated from the V-genes of two mouse parent hybridoma cell lines, with specificity against the P1.7 and P1.16 epitopes on the outer-membrane protein PorA on meningococci. The chimaeric antibodies can be used to analyse relationships between specificity, binding activity (avidity and kinetics), isotype (antibody class and antibody subclass) and in vitro anti-bacterial activity of meningococcal antibodies. The antibody sets represented the human isotypes IgG1, IgG3 and IgM, which dominate during immune response against protein antigens. The binding activities were quite similar for all these isotypes, surprisingly also for the pentameric IgM. Interestingly, monomeric IgM, prepared from pentameric IgM by partially reduction and alkylation, had similar binding activities as the original pentameric IgM. Regarding in vitro anti-bacterial activity, chIgG1 was superior in SBA (serum bactericidal activity) compared with chIgG3, while chIgG3 was more efficient in OP (opsonophagocytosis; measured by flow cytometry) than chIgG1. ChIgM showed slightly higher SBA than chIgG1 on molar basis, and much higher OP than chIgG3 and chIgG1. A lower concentration of antibodies was needed against the P1.16 than against the P1.7 epitope to induce SBA, but this was not the case for OP.

Anti-Bacterial Agents↗

PubMed2001

PorB3 outer membrane protein on Neisseria meningitidis is poorly accessible for antibody binding on live bacteria.

It is reported here that the PorB3 porin proteins of serotype 4 and 15 are poorly accessible for antibody binding on live Neisseria meningitidis bacteria, whereas the allelic PorB2 and the PorA outer membrane protein appear to be highly accessible. This was revealed by flow cytometry analysis using several mouse monoclonal antibodies (mAbs) as well as PorB3 specific antibodies isolated from post vaccination and patient sera. However, strong antibody binding to the PorB3 protein was observed after killing the bacteria with ethanol. The reason for the lack of epitope exposure could be a shielding effect of the carbohydrate chains of lipopolysaccharides (LPS) possibly combined with short extra-cellular loops in the PorB3 protein. The findings indicate that the PorB3 protein is not an optimal target for protective antibodies induced by vaccination.

Animals↗

PubMed2001

Epitope analyses of pneumococcal surface protein A: a combination of two monoclonal antibodies detects 94% of clinical isolates.

Immunisation of BALB/c mice with seven heat-treated Norwegian clinical isolates of Streptococcus pneumoniae of different serotypes elicited mainly monoclonal antibodies (mAbs) to pneumococcal surface protein A (PspA). It was remarkable that the fusions resulted only in a few mAbs directed against other protein antigens. Dot blot analysis with 16 mAbs using clinical isolates representing 23 different capsular types and the uncapsulated reference strain R36A showed that some of the mAbs bound to PspA epitopes expressed by a low number of strains whereas others bound to broadly distributed epitopes. On the basis of their reactivities, seven of these mAbs could be divided into two groups recognising different subsets of pneumococci. The three mAbs in the narrow reacting group bound to epitopes found in 21-25% of the strains whereas the four mAbs in the broad reacting group detected more than 57% of the analysed strains. The epitopes for these seven antibodies were surface exposed on live exponential phase grown pneumococci as shown by flow cytometry. The finding that a combination of mAb 180,C-1 (IgG2a) from the first group and mAb 170,E-11 (IgG2a) from the second group detected 94% of the examined strains is interesting because PspA has been reported by others to be a serological highly variable protein.

Animals↗

PubMed2000

Streptococcus pneumoniae heat shock protein 70 does not induce human antibody responses during infection.

Mouse monoclonal antibodies (mAbs) were developed against Streptococcus pneumoniae in search for potential common pneumococcal proteins as vaccine antigens. mAb 230,B-9 (IgG1) reacted by immunoblotting with a 70-kDa protein which was isolated by immunoaffinity chromatography and subsequent preparative electrophoresis. N-terminal amino acid sequencing showed homology to that of heat shock protein 70 (hsp70). The hsp70 epitope reactive with mAb 230,B-9 was found in all the pneumococci examined as well as in other streptococci and enterococci. The epitope was not expressed in several other examined Gram-positive or -negative bacteria. Pneumococcal hsp70 has by other investigators been proposed to be a vaccine candidate. Binding experiments using flow cytometry showed that the epitope was not surface-exposed on live exponential phase grown S. pneumoniae. Human patient sera did not react with affinity-purified pneumococcal hsp70. Therefore the pneumococcal hsp70 does not seem to be of special interest in a vaccine formulation. The human sera contained antibodies to high molecular proteins co-purified with hsp70. Some of these proteins could be the pneumococcal surface protein A.

Amino Acid Sequence↗

PubMed2000

Functional activities and immunoglobulin variable regions of human and murine monoclonal antibodies specific for the P1.7 PorA protein loop of Neisseria meningitidis.

The meningococcal PorA protein is considered a promising vaccine candidate. Although much is understood regarding the structure of PorA proteins, little is known about the structure-function relationships of PorA antibodies. The aim of this study was to compare the functional and molecular characteristics of a human monoclonal antibody (MAb) and three murine MAbs specific for the PorA P1.7 serosubtype. Murine MAbs 207,B-4 (immunoglobulin G2a [IgG2a]) and MN14C11.6 (IgG2a) were both bactericidal and opsonophagocytic for P1.7-expressing meningococci, whereas human MAb SS269 (IgG3) and murine MAb 208,D-5 (IgA) initiated neither effector function. Epitope mapping with synthetic peptides revealed that MAbs 207,B-4 and 208,D-5 recognized the sequence ASGQ, which is the same specificity motif that a previous study had established for SS269 and MN14C11.6. Nucleotide and amino acid sequence analyses of the variable regions of the four MAbs showed that the SS269 V(H) region belonged to the VH3 family and was approximately 70% homologous to those of the murine MAbs which were all from the 7183 family, whereas the SS269 V(L) region belonged to the Vlambda1-b family and was less than 40% homologous to those of the murine MAbs which were all members of the Vkappa1 family. The Fab fragment of SS269 was cloned and expressed in Escherichia coli and was shown by enzyme-linked immunosorbent assay analyses to bind as well as intact SS269 MAb to P1.7,16 serosubtype group B strain 44/76. We conclude that distinct differences exist in the effector function activities and variable region gene sequences of human and murine P1.7-specific MAbs despite their recognition of similar epitopes.

Amino Acid Sequence↗

PubMed2000

Mechanism for uptake of silica particles by monocytic U937 cells.

We examined the mechanism for uptake by monocytic cells of particles found in the atmosphere of some industrial work places. As a model system, irregular crystalline silica particles (SPs), sphere-like cryptocrystalline microsilica particles (MPs) and carbon particles (CPs) were exposed to pro-monocytic U937 cells. Plasma-treated SP and MP, but not CP, activated the alternative complement pathway, but bound little C3b. However, all particles adsorbed serum IgG, IgA and IgM unspecifically. Phenotyping of U937 cells for complement receptors (CRs) and Fcgamma receptors (FcgammaRs) showed that interferon gamma (INFgamma) increased expression of FcgammaRI, CR3 (CD11b/CD18) and CR4 (CD11c/CD18) and that phorbol-12-myristate-13-acetate (PMA) increased expression of CR4. Scanning electron microscopy (SEM) demonstrated higher phagocytosis of plasma-treated SP than native SP by both PMA- and INFgamma-stimulated, but not unstimulated, cells. MP and CP could not be distinguished from cellular structures. Inhibition experiments in SEM revealed uptake of heparin-plasma-treated SP via FcgammaRI on INFgamma-stimulated U937 cells, but could not exclude possible participation of CR3. The results indicate that plasma-treated SPs bind Ig and are internalized by differentiated monocytic cells via FcgammaRI, which is known to trigger cellular production of toxic oxygen species that may induce pulmonary inflammation in vivo.

Complement Activation↗

PubMed1999

Human IgG subclass responses in relation to serum bactericidal and opsonic activities after immunization with three doses of the Norwegian serogroup B meningococcal outer membrane vesicle vaccine.

Ten adult volunteers, with low prevaccination levels of serum IgG antibodies against meningococcal antigens (< 1 microg ml(-1)), received three doses of the Norwegian group B meningococcal outer membrane vesicle (OMV) vaccine intramuscularly at weeks 0, 6 and 46. Anti-OMV IgG subclass responses were measured and compared with serum bactericidal activity (SBA) and opsonic activity against the vaccine strain 44/76. All vaccinees showed an IgG1 antibody response after each vaccine dose. The vaccine-induced median serum IgG1 antibody levels were 16, 17 and 18 microg ml(-1) 2-6 weeks after the first, second and third dose, respectively. Three vaccinees showed a weak IgG3 response after the first dose, whereas 8 and 9 showed a response after the second (median = 10 microg ml(-1)) and third dose (median = 10 microg ml(-1)), respectively. Low levels of anti-OMV IgG2 antibodies were found, whilst specific IgG4 antibodies were only detected for one vaccinee. The vaccine induced at least a fourfold increase in SBA titre in 8 vaccinees after the first dose, in 9 vaccinees after 2 doses and in all vaccinees after 3 doses. A positive correlation was found between IgG1 subclass antibody levels and SBA (r = 0.62, P < 0.0001). Elevated opsonophagocytic activity, measured as respiratory burst (RB), was observed in all vaccinees after one vaccine dose and usually increased after 2 and 3 doses. A strong positive correlation was found between IgG1 antibody levels and RB (r = 0.76, P < 0.0001). In conclusion, we have shown that systemic meningococcal OMV vaccination in adult vaccinees mainly induced IgG1 antibodies which correlated with bactericidal and opsonic activity, but also a considerable amount of IgG3 antibodies, which, in contrast to the IgG1 response, was induced only after 2 or 3 vaccine doses and declined more rapidly.

Adult↗

PubMed1999

Antigen-specific T-cell responses in humans after intranasal immunization with a meningococcal serogroup B outer membrane vesicle vaccine.

We have studied the ability of the Norwegian group B meningococcal outer membrane vesicle (OMV) vaccine, when administered intranasally without adjuvant, to induce T-cell responses in humans. A group of 12 vaccinees was immunized with four doses of OMVs (250 micrograms of protein/dose) at weekly intervals, and a single booster dose was given 5 months later. In vitro T-cell proliferation in response to the OMV vaccine, purified PorA (class 1) protein, PorB (class 3) protein, and one unrelated control antigen (Mycobacterium bovis BCG) was measured by [3H]thymidine incorporation into peripheral blood mononuclear cells obtained from the vaccinees before and after the immunizations. The nasal OMV immunizations induced antigen-specific T-cell responses in the majority of the vaccinees when tested against OMVs (7 of 12) and the PorA antigen (11 of 12). None of the vaccinees showed a vaccine-induced T-cell response to the PorB antigen after the initial four doses. Although some individuals responded to all the vaccine antigens after the booster dose, this response was not significant when the vaccinees were analyzed as a group. We have also demonstrated that the PorA antigen-specific T-cell responses correlated with anti-OMV immunoglobulin A (IgA) levels in nasal secretions, with anti-OMV IgG levels in serum, and with serum bactericidal activity. In conclusion, we have shown that it is possible to induce antigen-specific T-cell responses in humans by intranasal administration of a meningococcal OMV vaccine without adjuvant.

Administration, Intranasal↗

PubMed1999

Functional activities and epitope specificity of human and murine antibodies against the class 4 outer membrane protein (Rmp) of Neisseria meningitidis.

Antibodies against the class 4 outer membrane protein (OMP) from Neisseria meningitidis have been purified from sera from vaccinees immunized with the Norwegian meningococcal group B outer membrane vesicle vaccine. The human sera and purified antibodies reacted strongly with the class 4 OMP in immunoblots, whereas experiments with whole bacteria showed only weak reactions, indicating that the antibodies mainly reacted with parts of the class 4 molecule that were not exposed. The purified human anti-class 4 OMP antibodies and the monoclonal antibodies (MAbs) were neither bactericidal nor opsonic against live meningococci. Three new MAbs against the class 4 OMP were generated and compared with other, previously described MAbs. Three linear epitopes in different regions of the class 4 OMP were identified by the reaction of MAbs with synthetic peptides. The MAbs showed no blocking effect on bactericidal activity of MAbs against other OMPs. However, one of the eight purified human anti-class 4 OMP antibody preparations, selected from immunoblot reactions among sera from 27 vaccinees, inhibited at high concentrations the bactericidal effect of a MAb against the class 1 OMP. However, these antibodies were not vaccine induced, as they were present also before vaccination. Therefore, this study gave no evidence that vaccination with a meningococcal outer membrane vesicle vaccine containing the class 4 OMP induces blocking antibodies. Our data indicated that the structure of class 4 OMP does not correspond to standard beta-barrel structures of integral OMPs and that no substantial portion of the OmpA-like C-terminal region of this protein is located at the surface of the outer membrane.

Adult↗

PubMed1998

Opsonophagocytic and bactericidal activity mediated by purified IgG subclass antibodies after vaccination with the Norwegian group B meningococcal vaccine.

To study how the different immunoglobulin (Ig)G subclass antibodies may confer protection against systemic meningococcal disease, we isolated IgG1, IgG2 and IgG3 antibodies from plasma from vaccinees immunized with the Norwegian meningococcal outer membrane vesicle vaccine. Four IgG1, one IgG2 and four IgG3 preparations were purified. The IgG2 and IgG3 subclass preparations were free from contaminating subclasses, whereas the IgG1 preparations contained from 0 to 14% of IgG2 and/or IgG3. Immunoblotting against whole-cell meningococcal antigens showed broad specificities of the various preparations, both within and between subclasses. These subclass preparations were tested for opsonophagocytic and bactericidal activity. As targets we used two different variants of the meningococcal vaccine strain, with low (44/76-SL) and high (44/76-1) expression of the outer membrane protein Opc. Using polymorphonuclear leucocytes as effector cells in the presence of human complement, all three IgG subclass preparations revealed high, and similar, opsonophagocytic activities against 44/76-SL, whereas against 44/76-1 the IgG2 preparation showed a reduced activity and most IgG3 preparations were slightly more active than the IgG1 preparations. Regarding bactericidal activity, all the three subclasses were highly active against 44/76-SL. Against 44/76-1 the bactericidal activities were somewhat more varied: all IgG1 and three IgG3 preparations exhibited higher activities than against 44/76-SL. Due to the low concentration in the IgG2 preparations, only a weak activity was seen against 44/76-1. One IgG3 preparation that was highly opsonophagocytic revealed no bactericidal activity against either of the two bacterial variants examined. In conclusion, we have shown that the IgG subclass effector functions differ from person to person, but that antibodies of IgG1, IgG2 and IgG3 subclasses, judged by their behaviour in the functional tests, may all contribute to protection against meningococcal disease.

Antibody Specificity↗

PubMed1998

Human T-cell responses after vaccination with the Norwegian group B meningococcal outer membrane vesicle vaccine.

We have analyzed human T-cell responses in parallel with serum immunoglobulin G (IgG) antibody levels after systemic vaccination with the Norwegian group B Neisseria meningitidis outer membrane vesicle (OMV) vaccine. Ten adult volunteers, with no or very low levels of serum IgG antibodies against meningococci, received three doses intramuscularly of the OMV vaccine (at weeks 0, 6, and 46). T-cell proliferation against the OMV vaccine, purified outer membrane proteins (PorA and PorB), and control antigens (Mycobacterium bovis BCG vaccine and tetanus toxoid) was measured by thymidine incorporation of peripheral blood mononuclear cells before and after vaccination. The results showed that vaccination with OMV elicits strong primary and booster T-cell responses specific to OMV as well as the PorA (class 1) protein and significant, but markedly lower, responses against the PorB (class 3) protein. The median responses to OMV and PorA were 26 and 16 times the prevaccination levels, respectively. Most of the vaccinees showed low T-cell responses against OMV and PorA before vaccination, and the maximum T-cell responses to all vaccine antigens were usually obtained after the second vaccine dose. We found a positive correlation between T-cell responses and anti-OMV IgG antibody levels (r = 0.50, P < 0.0001, for OMV and PorA). In addition, we observed a progressive increase in the percentage of CD45R0+ (memory) CD4-positive T cells (P = 0.002). In conclusion, we have shown that the Norwegian OMV vaccine against meningococcal B disease induced antigen-specific T-cell responses, kinetically accompanied by serum IgG responses, and that vaccination increased the proportion of memory T-helper cells.

Adult↗

PubMed1998

Intranasal administration of a meningococcal outer membrane vesicle vaccine induces persistent local mucosal antibodies and serum antibodies with strong bactericidal activity in humans.

A nasal vaccine, consisting of outer membrane vesicles (OMVs) from group B Neisseria meningitidis, was given to 12 volunteers in the form of nose drops or nasal spray four times at weekly intervals, with a fifth dose 5 months later. Each nasal dose consisted of 250 microg of protein, equivalent to 10 times the intramuscular dose that was administered twice with a 6-week interval to 11 other volunteers. All individuals given the nasal vaccine developed immunoglobulin A (IgA) antibody responses to OMVs in nasal secretions, and eight developed salivary IgA antibodies which persisted for at least 5 months. Intramuscular immunizations did not lead to antibody responses in the secretions. Modest increases in serum IgG antibodies were obtained in 5 volunteers who had been immunized intranasally, while 10 individuals responded strongly to the intramuscular vaccine. Both the serum and secretory antibody responses reached a maximum after two to three doses of the nasal vaccine, with no significant booster effect of the fifth dose. The pattern of serum antibody specificities against the different OMV components after intranasal immunizations was largely similar to that obtained with the intramuscular vaccine. Five and eight vaccinees in the nasal group developed persistent increases in serum bactericidal titers to the homologous meningococcal vaccine strain expressing low and high levels, respectively, of the outer membrane protein Opc. Our results indicate that meningococcal OMVs possess the structures necessary to initiate systemic as well as local mucosal immune responses when presented as a nasal vaccine. Although the serum antibody levels were less conspicuous than those after intramuscular vaccinations, the demonstration of substantial bactericidal activity indicates that a nonproliferating nasal vaccine might induce antibodies of high functional quality.

Administration, Intranasal↗

PubMed1998

Towards a nasal vaccine against meningococcal disease, and prospects for its use as a mucosal adjuvant.

A Norwegian outer membrane vesicle (OMV) vaccine against group B meningococcal disease proved to be strongly immunogenic when administered intranasally in mice. The OMV preparation, made from Neisseria meningitidis and intended for parenteral use, was therefore given without adjuvant to human volunteers (n = 12) in the form of nose drops or nasal spray. Such immunizations, which were carried out at weekly intervals during a three-week period, were able to induce systemic antibodies with bactericidal activity in more than half of the individuals. In addition, all vaccinees developed marked increases in OMV-specific IgA antibodies in nasal secretions. The potential of the OMV particles as carriers for other less immunogenic antigens were elucidated in mice with use of whole inactivated influenza virus. Even though influenza virus alone did induce some systemic and salivary antibody responses after being administered intranasally, these responses were greatly augmented when the virus was presented together with OMVs. Thus, it is possible that a nasal OMV vaccine may induce protection against invasive meningococcal disease, and also that it might be used as a vehicle for nasal vaccines against other diseases.

Adjuvants, Immunologic↗

PubMed1998

Effect of aluminium hydroxide and meningococcal serogroup C capsular polysaccharide on the immunogenicity and reactogenicity of a group B Neisseria meningitidis outer membrane vesicle vaccine.

Three different formulations of an outer membrane vesicle (OMV) vaccine against group B meningococcal disease have been prepared and tested for immunogenicity and reactogenicity in adult volunteers. The vaccines were prepared with or without aluminium hydroxide and serogroup C-polysaccharide (C-ps). Doses from 12.5 to 100 micrograms protein were given twice at a six weeks' interval. All three formulations were well tolerated and highly immunogenic, inducing bactericidal and opsonizing antibodies in humans. Adsorption of OMVs to aluminium hydroxide reduced the pyrogenicity in rabbits. The differences in immunogenicity between the formulations were relatively small, but after the second dose a stronger booster response was observed when the vaccines were adsorbed. Thus, a formulation with OMVs and C-ps represents a safe and highly immunogenic vaccine, even without aluminium hydroxide.

Adjuvants, Immunologic↗

PubMed1997

Vaccine-induced IgG antibodies to the linear epitope on the PorB outer membrane protein promote opsonophagocytosis of Neisseria meningitidis by human neutrophils.

The serotype 15 PorB protein of Neisseria meningitidis contains an N-terminal linear immunodominant B-cell epitope located on the putative loop 1 (VR1) region. This epitope has previously been shown to stimulate antibody formation in 74% of the vaccinees after three doses of the Norwegian group B outer-membrane vesicle (OMV) vaccine. In the present study, the purified PorB protein and the 23mer synthetic peptide D63b2 covering VR1 region were immobilized onto N-hydroxysuccinimide-activated matrix and used for affinity purification of the specific IgG antibodies from sera of three selected vaccinees. PorB- and peptide D63b2-specific IgG preparations bound to the PorB protein on immunoblots and reacted with strain 44/76 and OMV complexes expressing the serotype 15 PorB protein, but not with the PorB-deficient mutant, suggesting high specificity for the PorB protein. Both PorB- and peptide D63b2-specific IgG were marginally bactericidal, but enabled strong opsonophagocytosis measured as respiratory burst response of human neutrophils and internalization of opsonized FTTC-labeled meningococci. The data indicate that about 30-57% of the bulk serum opsonic activity for the 44/76 bacteria could be ascribed to linear epitope-specific IgG1, thus contributing to vaccine-induced protection against systemic meningococcal disease via the opsonophagocytic route of pathogen clearance.

Adult↗

PubMed1997

Outer membrane vesicle vaccines made from short-chain lipopolysaccharide mutants of serogroup B Neisseria meningitidis: effect of the carbohydrate chain length on the immune response.

Outer membrane vesicle (OMV) vaccines were made from Neisseria meningitidis strain 44/76 and its two short-chain lipopolysaccharide (LPS) mutants, Mu-1 and Mu-4. Only the 44/76 vaccine contained LPS with the host antigen lacto-N-neotetraose. The protein composition of the vaccines was similar. The LPS carbohydrate chain length proved to influence drastic changes in the LPS immunogenicity as well as the outer membrane proteins (OMPs) ability to elicit functional antibodies in mice. Only LPS in the Mu-1 and Mu-4 vaccines were immunogenic, and the 44/76 vaccine differed also by not inducing antibodies to the class 4 OMP. The Mu-1 vaccine, with a LPS carbohydrate chain comprising only two residues of 2-keto-3-deoxy-octonic acid, induced lower bactericidal activity and less antibodies to the class 1 OMP, compared to the two other vaccines. This indicates that LPS of a certain carbohydrate chain length is required for adequate exposure of the class 1 OMP epitopes essential for inducing bactericidal antibodies.

Animals↗