Effect of race and blood group on the immune response to bacterial polysaccharide and conjugate vaccines.
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Adolescent↗
Biomedical subjects
J C Sadoff
Publications and source records attributed to J C Sadoff.
Synthesis and characterization of gentiobiose heptaacetate conjugate vaccines that produce endotoxin-neutralizing antibodies.
We have prepared aminoethyl (AE), aminopropyl (AP), and aminopentyl (APT) derivatives of gentiobiose heptaacetate (GH). These spacer compounds (AEGH, APGH, APTGH) have been coupled to succinylated diphtheria toxoid (Suc.DT) to produce conjugate vaccines. These conjugates all bind to the anti-lipid A human monoclonal antibody A6(H4C5) in an ELISA binding assay. Rabbits immunized with the APGH conjugate vaccine in either Freund's complete adjuvant or aluminum hydroxide gel produced antibody levels of 5120 and 3600 ELISA units, respectively, compared to an antibody level of less than 20 ELISA units for the prebleed sera. Sera from mice immunized with either the aminopropyl or the aminopentyl conjugate had antibody levels of 5120 and 2560 ELISA antibody units, respectively. These antibodies neutralized endotoxin in a Limulus lysate neutralization assay. Protection against the local Shwartzman reaction was demonstrated (p less than 0.05) in eight out of nine rabbits immunized with the Suc-DT-APGH conjugate vaccine compared to three out of 10 rabbits immunized with the carrier protein Suc-DT. Passive transfer experiments demonstrated that four out of five rabbits receiving immune serum were protected from Shwartzman reaction compared to one out of five rabbits receiving normal serum (p less than 0.1). These results indicated that epitopes contained in gentiobiose heptaacetate when properly presented as conjugate vaccines were capable of inducing neutralizing antibodies against endotoxin.
Amines↗
Active and passive immunization strategies for Pseudomonas aeruginosa pneumonia.
The unusually high mortality associated with Pseudomonas aeruginosa pneumonia has provided an incentive for the development of immunologic strategies for preventing or treating this infection. A guinea pig model of experimental P. aeruginosa pneumonia was employed to determine prophylactic efficacy of active immunization with a detoxified lipopolysaccharide vaccine; efficacy of passive immune therapy utilizing a new hyperimmune immunoglobulin G preparation enriched for antibodies to P. aeruginosa immunotypes 1, 2, 4, and 6; and efficacy of active and passive immunization against the mucoid exopolysaccharide antigen associated with mucoid strains of P. aeruginosa. Each of these immunologic methods provided an element of protection against P. aeruginosa pneumonia.
Animals↗
Use of Pseudomonas aeruginosa toxin A in the construction of conjugate vaccines and immunotoxins.
Pseudomonas aeruginosa toxin A was used to construct conjugate vaccines and potent cytotoxic immunotoxins. Nontoxic, serologically active O polysaccharide derived from P. aeruginosa lipopolysaccharide (LPS) was covalently coupled to toxin A via reductive amination. The conjugate was nontoxic, nonpyrogenic, and had a molecular size of 2 X 10(6). The conjugate vaccine was safe when administered to human volunteers and was capable of evoking an immune response to both LPS and toxin A. Native toxin A was coupled to monoclonal antibodies to the human transferrin receptor and the human interleukin 2 receptor to produce immunotoxins active against receptor-bearing cell lines. Antitumor activity was demonstrated when the immunotoxin directed against the transferrin receptor was administered to nude mice bearing human ovarian tumors.
ADP Ribose Transferases↗