ABSTRACT
This report describes the results of a phase 1 study evaluating the safety, infectivity, and immunogenicity of a new live oral Salmonella typhi temperature-sensitive (ts) 51-1 typhoid fever vaccine in the human. Three normal male subjects aged 23-32 years received three oral doses of S. typhi ts 51-1, each dose containing 10(9) organisms. Prior to and following immunization each subject was carefully monitored by clinical and laboratory parameters over a 2 week period during which serial specimens of blood and stool were analysed for the presence of the organism. Blood specimens were also obtained for the determination of serum antibody and cell-mediated immune responses and stool filtrates were analysed for the development of coproantibody. The results of these studies indicate that: (1) the vaccine is well tolerated with no clinical or laboratory evidence of adverse reactions; (2) ts 51-1 was detected in only one stool specimen from one volunteer; the organism recovered displayed characteristics of the ts 51-1 vaccine strain; and (3) although no significant humoral or cell-mediated lymphocytotoxic immune responses were detected in the blood, coproantibody was detected in stool specimens from all of the three immunized subjects and IgA-armed ADCC activity was detected in two of three subjects. These studies indicate that S. typhi ts 51-1 may be a suitable strain for the development of an improved oral typhoid fever vaccine. Studies are in progress to determine optimal methods of vaccine delivery preparatory to large phase 2 studies of efficacy.
Subject(s)
Antibodies, Bacterial/analysis , Salmonella typhi/immunology , Typhoid-Paratyphoid Vaccines/immunology , Administration, Oral , Adult , Antibody-Dependent Cell Cytotoxicity , Enzyme-Linked Immunosorbent Assay , Humans , Male , Mutation , Salmonella typhi/genetics , Temperature , Typhoid-Paratyphoid Vaccines/administration & dosage , Vaccines, Attenuated/immunologyABSTRACT
A clone of poliovirus type III (TRU-3) was derived from the Sabin-3 vaccine strain by the cDNA:RNA hybrid molecular cloning method. The virus recovered was found to be considerably less neurovirulent for primates than its progenitor Sabin III vaccine strain. Upon serial passages in humans, TRU-3 did not increase its neurovirulence (unlike the Sabin strain) and maintained the base sequence of the attenuated strain in a critical part of the 5' region of the genome (unlike the Sabin strain). The substitution of TRU-3 clone for Sabin type III in oral polio vaccine could eliminate the vast majority of cases of vaccine-associated poliomyelitis.
Subject(s)
Poliovirus Vaccine, Oral/genetics , Poliovirus/pathogenicity , Animals , Base Sequence , Humans , Poliovirus/isolation & purification , Recombination, Genetic , VirulenceSubject(s)
Lymphoma, Non-Hodgkin/etiology , Lymphoma, Non-Hodgkin/veterinary , Rabbits , Animals , Animals, Domestic , Antigens, Viral , Bone Marrow/pathology , Centrifugation, Density Gradient , Immunodiffusion , Kidney/pathology , Liver/pathology , Lymph Nodes/pathology , Lymphoma, Non-Hodgkin/pathology , Male , Retroviridae/immunology , Spleen/pathologyABSTRACT
Feline leukemia-sarcoma group-specific antigens were located in human embryo cells infected with feline leukemia and feline sarcoma viruses. This was done by using the fluorescent-antibody and enzyme-labeled antibody techniques at both light and electron microscopic levels. The antigens were found to be exclusively intracytoplasmic, diffuse, and located in discrete punctate foci.
