ABSTRACT
Three separate studies were undertaken in HIV-1 uninfected persons to determine if the adjuvant QS-21 improves the magnitude or kinetics of immune responses induced by recombinant soluble gp120 HIV-1(MN) protein (rsgp120) immunization. The QS-21 was administered at two doses (50 and 100 microg), either alone or in combination with aluminum hydroxide (600 microg). At the highest doses of rsgp120 (100, 300, and 600 microg), QS-21 exerted no significant effect on either binding or neutralizing antibody titers. Antibody binding and neutralizing responses fell dramatically when rsgp120, formulated with alum alone, was given at low doses (3 and 30 microg). In contrast, antibody responses similar in titer to those in the high dose antigen groups were induced with the low dose rsgp120 formulated with QS-21. In addition, the lymphocyte proliferation and delayed type hypersensitivity skin testing were superior in the QS-21 recipients compared with the alum recipients at the low antigen doses. Moderate to severe pain was observed in majority of the volunteers receiving QS-21 formulations, and vasovagal episodes and hypertension were not infrequent. Thus, the use of QS-21 may provide a means to reduce the dose of a soluble protein immunogen.
Subject(s)
AIDS Vaccines/administration & dosage , Adjuvants, Immunologic/administration & dosage , HIV Envelope Protein gp120/administration & dosage , Saponins/administration & dosage , AIDS Vaccines/adverse effects , AIDS Vaccines/isolation & purification , Adolescent , Adult , Aluminum Hydroxide/administration & dosage , Animals , CHO Cells , Cricetinae , HIV Antibodies/biosynthesis , HIV Envelope Protein gp120/isolation & purification , Humans , Hypersensitivity, Delayed , Immunization , In Vitro Techniques , Lymphocyte Activation , Middle Aged , Safety , T-Lymphocytes, Cytotoxic/immunology , Vaccines, Synthetic/administration & dosage , Vaccines, Synthetic/adverse effects , Vaccines, Synthetic/isolation & purificationABSTRACT
The fusion glycoproteins of human respiratory syncytial virus (RSV) and human parainfluenza virus type-3 (PIV-3) mediate virus entry and syncytium formation. Interaction between the fusion protein of RSV and RhoA, a small GTPase, facilitates virus-induced syncytium formation. We show here a RhoA-derived peptide inhibits RSV and syncytium formation induced by RSV and PIV-3, both in vitro by inhibition of cell-to-cell fusion and in vivo by reduction of peak titer by 2 log10 in RSV-infected mice. These findings indicate that the interaction between these two paramyxovirus fusion proteins and RhoA is an important target for new antiviral strategies.
Subject(s)
Giant Cells/physiology , Parainfluenza Virus 3, Human/physiology , Peptide Fragments/pharmacology , Respiratory Syncytial Virus Infections/physiopathology , Respiratory Syncytial Virus, Human/physiology , rhoA GTP-Binding Protein/physiology , Amino Acid Sequence , Animals , Cell Fusion , Cells, Cultured , Enzyme-Linked Immunosorbent Assay , Giant Cells/drug effects , Giant Cells/virology , Humans , Mice , Mice, Inbred BALB C , Molecular Sequence Data , Parainfluenza Virus 3, Human/drug effects , Parainfluenza Virus 3, Human/genetics , Peptide Fragments/chemistry , Respiratory Syncytial Virus, Human/drug effects , Respiratory Syncytial Virus, Human/genetics , Vaccinia virus/physiology , rhoA GTP-Binding Protein/chemistryABSTRACT
Staphylococcal toxic shock syndrome has been reported in a number of nonmenstrual settings, including orthopedic patients with postoperative staphylococcal wound infections. We describe two cases of toxic shock syndrome in children with focal cutaneous staphylococcal infections occurring beneath casts placed for limb immobilization. These cases illustrate a new and potentially hidden site of staphylococcal infection leading to toxic shock syndrome.
