TL;DR: Comparison of the humoral immune responses of normal BALB/c mice and autoimmune NZB mice to hyperimmunization showed that, although both strains mounted a weak meningococcal B polysaccharide-specific IgM response, only the NZB strain mounted an IgG response.
Abstract: A system for the production of monoclonal antibodies, particularly of the IgG type, against weakly immunogenic bacterial polysaccharide antigens is described. This system, which is based on the autoimmune NZB mouse strain, has been used to produce a monoclonal IgG2a antibody against the meningococcus group B and Escherichia coli K1 polysaccharides, identical homopolymers of alpha (2----8)-linked units of N-acetylneuraminic acid that are extremely poor immunogens. Comparison of the humoral immune responses of normal BALB/c mice and autoimmune NZB mice to hyperimmunization with group A, B, and C meningococci showed that, although both strains mounted a weak meningococcal B polysaccharide-specific IgM response, only the NZB strain mounted an IgG response. Similarly, NZB mice mounted a stronger IgG response to the more immunogenic group C meningococcal polysaccharide than did BALB/c mice, although this difference was less pronounced than that observed with meningococcal B polysaccharide. No difference between the two strains of mice was demonstrable with the strongly antigenic group A meningococcal polysaccharide. These results indicate that the NZB system may be generally useful for the production of monoclonal antibodies against weakly antigenic bacterial determinants.
TL;DR: Hyperimmunization of mice with the groups A and C polysaccharide-tetanus toxoid conjugate produced antisera with good bactericidal activity against their respective homologous organisms, and indicated the potential of these conjugates as potential human vaccines.
Abstract: The successful coupling of the meningococcal groups A, B, and C polysaccharides to tetanus toxoid to yield water soluble conjugates is described. Reactive aldehyde groups were strategically introduced into the terminal residues of the polysaccharides by the controlled periodate oxidation of the native groups B and C polysaccharides and of the group A polysaccharide previously modified by the reduction of its terminal reducing N-acetyl-mannosamine residue. This produced essentially monovalent polysaccharide molecules, which were subsequently covalently linked to tetanus toxoid by means of reductive amination. Although the groups A and C polysaccharides proved to be poor immunogens in rabbits and mice, their tetanus toxoid conjugates produced high levels of polysaccharide-specific antibodies in both animals. By contrast, even in the form of its tetanus toxoid conjugate, the group B polysaccharide failed to elicit homologous polysaccharide-specific antibodies in either animal; a major proportion of the antibodies actually produced had a specificity for the linkage area of the conjugate. This evidence is compatible with the hypothesis of the poor immunogenicity of the group B polysaccharide being structure related. Hyperimmunization of mice with the groups A and C polysaccharide-tetanus toxoid conjugates produced antisera with good bactericidal activity against their respective homologous organisms, and indicated the potential of these conjugates as potential human vaccines.
TL;DR: Thymus (T) lymphocytes are involved in the resistance to infection with the facultative intracellular bacteria L. monocytogenes, and Hyperimmunization of the donor reduces the number of cells necessary to transfer effective immunity.
Abstract: Spleen cells of mice infected with Listeria monocytogenes were adoptively transferred to normal mice. Such lymphocytes conferred resistance to a lethal challenge with Listeria. Hyperimmunization of the donor reduces the number of cells necessary to transfer effective immunity. Such spleen cells if treated with anti-theta serum do not transfer resistance to Listeria. Hence, thymus (T) lymphocytes are involved in the resistance to infection with the facultative intracellular bacteria L. monocytogenes.
TL;DR: Induction of a protective immune response by NS1 suggests that it be considered for incorporation into possible synthetic or recombinant DNA DEN vaccines.
Abstract: Summary
Immunization of mice with the dengue 2 virus (DEN 2)-specified non-structural protein NS1 provided significant protection against intracerebral challenge with the virus in the absence of detectable neutralizing or other anti-virion antibody. NS1, purified from lysates of infected Vero cells by immunoaffinity chromatography, expressed an antigenic site(s) common to each of the four DEN serotypes, and hyperimmunization of rabbits with NS1 stimulated production of complement-fixing (CF) antibody with broad DEN serotype specificity. However, cross-protection was not observed: mice immunized with DEN 2 NS1 developed little or no heterologous CF antibody and were not protected against challenge with neurovirulent DEN 1. Induction of a protective immune response by NS1 suggests that it be considered for incorporation into possible synthetic or recombinant DNA DEN vaccines.
TL;DR: The strategies described for identifying and analyzing the specificity of MoAbs demonstrate the feasibility of developing a set of cross reactive MoAbs for identifying homologous molecules in multiple species and delineating their functional and phylogenetic relation.