Search PubMed⌕ Search

Biomedical subjects

S A Plotkin

Publications and source records attributed to S A Plotkin.

At least 19 recordsLinked to original sources
PubMed1995

A new typhoid vaccine composed of the Vi capsular polysaccharide.

Typhoid is still prevalent in many parts of the world. We reviewed all published and unpublished studies of a newly licensed vaccine composed of the Vi capsular polysaccharide of Salmonella typhi, the causative agent of the disease, which had been licensed previously outside the United States. These included observational studies and double-blind randomized studies done in the United States, Europe, and the developing world in which children and adults unexposed to typhoid or those living in endemic areas were enrolled. A single dose of 25 micrograms of the purified polysaccharide was given by intramuscular injection. The vaccine was well tolerated, inducing only minor reactions in fewer than 10% of subjects. An antibody response occurred in about 90% of subjects and lasted about 3 years. Seroconversion was shown in children as young as 2 years. Protective efficacy was evaluated in two studies conducted in areas in which typhoid is endemic; the efficacy was 55% and 75%, respectively, in adults and in children older than 5 years. The Vi vaccine compares favorably with other typhoid vaccines in regard to safety, patient compliance, immunogenicity, and efficacy. Vi polysaccharide is a well-standardized antigen that is effective in a single parenteral dose, is safer than whole-cell vaccine, and may be used in children 2 years of age or older.

Adult↗
PubMed1995

Preclinical evaluation of an ALVAC (canarypox)--human cytomegalovirus glycoprotein B vaccine candidate.

Successful vaccination against the human cytomegalovirus (HCMV) requires induction of both neutralizing antibody and cytotoxic T lymphocyte (CTL) responses. The HCMV glycoprotein B (gB, UL55) would be one of the most important immunogens to induce neutralizing antibodies. We tested the immunogenicity of an ALVAC (canarypox)-HCMV-gB (ALVAC-gB) recombinant in mice and guinea pigs in order to provide preclinical data for a phase I clinical trial of a HCMV vaccine candidate. ALVAC is an attenuated vaccine strain of canarypox virus which replicates productively in avian species but abortively in mammalian cells. The ALVAC-gB recombinant inoculated subcutaneously in mice and intramuscularly in guinea pigs induced HCMV-specific neutralizing antibodies and gB-specific CTL responses. Ultraviolet irradiation of the ALVAC-gB recombinant before immunization diminished CTL responses, indicating that intracellular expression and processing of gB-protein were necessary for CTL induction. Prior immunity to vaccinia virus did not decrease immunogenicity of the ALVAC-gB recombinant in mice. Thus, despite its host range restriction, ALVAC-gB is potentially capable of inducing both humoral and cell-mediated immune responses to HCMV in both vaccinia-immune and non-immune individuals.

Animals↗
PubMed1995

Immunity induced by primary human cytomegalovirus infection protects against secondary infection among women of childbearing age.

To determine if immunity to human cytomegalovirus (HCMV) protects women from acquiring HCMV from their children, a blinded, randomized protocol was used to monitor seronegative women who received placebo or Towne vaccine (approximately 500 pfu) and seropositive women. Each group was similar for mean maternal (33 years) and child age (18 months) and duration of viral shedding by the child (15 months). Among 19 placebo recipients, 9 developed primary infection; 8 of 19 vaccines but only 3 of 42 naturally seropositive subjects had evidence of acquiring HCMV from their child. Wild type infection and Towne vaccine induced similar mean lymphoproliferative responses to HCMV antigens, but one dose of Towne vaccine produced mean neutralizing titers 10- to 20-fold lower than those after wild type infection. Thus, a vaccine that induces immune responses equal to those induced by wild type virus may protect healthy women from acquiring HCMV from their children.

Adult↗
PubMed1995

Rubella vaccine.

Explore the source record for details and available documents.

Arthritis↗
PubMed1995

The safety and use of canarypox vectored vaccines.

ALVAC recombinants have been administered to humans and animals by parenteral and oral routes without giving signs of replication, systemic dissemination or severe reaction. In principle, it should be impossible for canarypox recombinants to disseminate in the environment as they would not be synthesised in mammalian cells as complete virus. Canarypox vectors have been safe for humans, in whom there has been no evidence of replication, but more work needs to be done to prove absence of replication. Recombinants are immunogenic by the intramuscular and subcutaneous routes. They are also immunogenic when given orally, but the dose required is still under study. Canarypox recombinants effectively prime the immune system for induction of antibodies and CD8 cell-mediated cytotoxicity by protein antigens. Antibody responses are not influenced by prior inoculation of canarypox, of subunit vaccine corresponding to the gene insert, or of vaccinia. Canarypox virus is attenuated for canaries, in which species it is already widely used. In principle, it is non-infectious for humans or other mammals. It may be infectious for other birds.

AIDS Vaccines↗
PubMed1994

Multicenter trial of Towne strain attenuated virus vaccine in seronegative renal transplant recipients.

The Towne strain of attenuated CMV vaccine was compared with placebo in seronegative renal transplants who later received kidneys from seropositive donors. This was a double-blind, randomized, placebo-controlled trial conducted at 3 different institutions. The results were consistent with 2 prior studies, in that whereas mild CMV disease was only slightly and insignificantly reduced in vaccine recipients, severe disease was markedly reduced. In the current study, all 4 severe cases of CMV disease occurred in placebo recipients, for an incidence of 17%, versus 0% in vaccine recipients (P < 0.03). Thus, prior immunization rendered seronegative patients more resistant to the effects of CMV infection.

Cytomegalovirus↗
PubMed1994

Early region 3-replacement adenovirus recombinants are less pathogenic in cotton rats and mice than early region 3-deleted viruses.

BACKGROUND: Adenovirus type-5 (Ad5) recombinant viruses with replacement of the 1.9 kb XbaI fragment in the early region 3 (E3) by foreign genes have been constructed with the ultimate goal of inducing immune responses to the product of the inserted gene against a variety of virus infections. The pathogenicity of these recombinants, however, has not been studied. EXPERIMENTAL DESIGN: Histopathologic changes induced in cotton rat and mouse lung by E3-replacement-Ad5 recombinant or wild-type Ad (Wt-Ad) or E3-deleted mutant (Ad5-delta E3) viruses were compared. Expression of viral mRNA and replication of these viruses in cotton rat and mouse lungs, as well as in human tissue culture cells, were assayed. Expression of class I major histocompatibility complex antigens and the E3-14.7 kilodalton protein in virus-infected cells were also analyzed. RESULTS: An Ad5 recombinant, Ad-human cytomegalovirus glycoprotein B (Ad-HCMV.gB), in which the E3 region is replaced by the full-length gB gene of HCMV and with a genome size exceeding that of Wt-Ad, induced mild histopathologic responses in cotton rat and mouse lungs, comparable with those of Wt-Ad, but less severe than those of Ad5-delta E3. Analysis indicated that neither class I major histocompatibility complex expression on the cell surface nor differential expression of the protective E3-14.7 kilodalton protein underlies the pathologic differences observed in cells infected with Ad5-delta E3 or the Ad-HCMV.gB recombinant. In the mouse lung, another Ad-E3 replacement recombinant, Ad-herpes simplex glycoprotein B (HSV.gB), containing the complete HSV.gB gene and with a genome size larger than that of Wt-Ad, also induced a very mild inflammatory response. However, two recombinants with truncated forms of the HCMV.gB (Ad-HCMV.gB.155) or HSV.gB genes (Ad-HSV.gB.147) produced more severe histopathologic changes than the Wt-Ad or the recombinants with the full complement of HCMV.gB or HSV.gB genes. Ad5 and some of the recombinants replicated in mouse and cotton rat lung, and the extent of replication was inversely proportional to genome size, both in the lung and in human tissue culture cells. Infectious virus titers were, however, higher in cotton rat than in mouse lung. In situ hybridization analysis of cotton rat and mouse lung infected with Wt-Ad, Ad5-delta E3, or Ad-HCMV.gB virus revealed expression of Ad early/late mRNA predominantly in bronchial epithelial cells. CONCLUSIONS: These data not only confirm that E3-deleted viruses induce more severe pathologic changes in cotton rat lungs than Wt-Ad viruses (Ginsberg et al., Proc Natl Acad Sci USA 1989;86:3823-7) but led to the observation that some E3 replacement recombinants also lacking the expression of the 19 and 14.7 kilodalton proteins are significantly less pathogenic in cotton rats and mice than an E3-deleted virus. Pathogenicity and replication of the recombinant viruses inversely correlate with the genomic size.

Adenoviridae↗
PubMed1993

Murine cytotoxic T cell response specific for human cytomegalovirus glycoprotein B (gB) induced by adenovirus and vaccinia virus recombinants expressing gB.

A murine model of the cytotoxic T lymphocyte (CTL) response to glycoprotein B (gB) of human cytomegalovirus (HCMV) was developed based on the use of adenovirus (Ad) and vaccinia virus (Vac) recombinants expressing gB. Mice of different major histocompatibility haplotypes [CBA (H-2k), BALB/k (H-2k) and BALB/c (H-2d)] infected with the Ad-gB recombinant developed an Ad-specific CTL response. However, only the H-2k mice developed a significant HCMV gB-specific CTL response, as indicated by the major histocompatibility complex class I-restricted lysis of Vac strain Copenhagen (VacC)-gB recombinant-infected target cells by H-2k mouse immune spleen cells. The VacC-gB recombinant elicited only a weak gB-specific CTL response in these mice, indicating that the observed gB-specific CTL response in mice is dependent on the expression vector used for immunization. The gB-specific cytotoxicity observed in H-2k mice was mediated by the CD8 lymphocyte subset.

Adenoviridae↗
PubMed1991

Isolation and characterization of an infectious molecular clone of the MN strain of HIV-1.

Infectious molecular clones of the human immunodeficiency virus (HIV) have been very important tools for the analysis of regulatory gene functions and the study of differential cell tropism. We have cloned and characterized a proviral sequence of HIVmn from mn strain infected H9 cells. This clone, called KP1, was found to be infectious for different cell lines and human peripheral blood lymphocytes (PBL). KP1 proviral DNA was detected in HUT-78 cells and human PBL by polymerase chain reaction (PCR) analysis after infection of these cells with cell-free supernatants from KP1 transfected human rhabdomyosarcoma (RD) cells. To the best of our knowledge, this is the first report of an infectious molecular clone of HIVmn which is a representative of one of the most prevalent strains of HIV-1 in North America and Europe. Biologically active clones of a broadly antigenic strain such as HIVmn will be extremely useful in therapeutic approaches for AIDS.

Base Sequence↗
PubMed1991

Effect of Towne live virus vaccine on cytomegalovirus disease after renal transplant. A controlled trial.

OBJECTIVE: To test the efficacy of vaccination with the Towne live attenuated cytomegalovirus vaccine. DESIGN: A double-blind, randomized, placebo-controlled trial in candidates for renal transplantation. The cytomegalovirus serologic status of both recipients and donors were determined, and the recipients were followed for periods of 6 months to 7 years after transplant. SETTING: A university transplant center. PATIENTS: The analyses were made on 237 patients who were given either vaccine or placebo, received renal transplants, and were followed for at least 6 months. INTERVENTION: Subcutaneous inoculation with Towne live attenuated virus or with placebo. MAIN OUTCOME MEASURES: The presence of cytomegalovirus infection was defined by virus isolation and antibody tests. If infection occurred, a prearranged scoring system for cytomegalovirus disease was used to objectify disease severity. RESULTS: The vaccine was well tolerated, and there were no discernible long-term adverse effects. Recipients who were originally seropositive did not clearly benefit from vaccination. Protective efficacy was analyzed in the group at highest risk for cytomegalovirus disease; recipients who were seronegative at the time of vaccination and who received a kidney from a seropositive donor. Compared with placebo recipients, vaccinated patients in this group had significantly less severe cytomegalovirus disease, with a significant reduction in disease scores (P = 0.03) and 85% decrease in the most severe disease (95% CI, 35% to 96%), although infection rates were similar. Graft survival at 36 months was improved in vaccinated recipients of cadaver kidneys (8 of 16) compared with unvaccinated recipients (4 of 16) (P = 0.04). CONCLUSIONS: Previous vaccination of seronegative renal transplant recipients with live cytomegalovirus results in reduction of disease severity mimicking the action of naturally derived immunity.

Adult↗
PubMed1991

Minitransfection: a simple, fast technique for transfections.

A fast, simple and inexpensive minitransfection technique, using either a lipofection or a calcium phosphate coprecipitation method to introduce foreign DNA into living cells is presented. This technique is based on the use of 24-well or 96-well tissue culture plates and can be used for both transient and stable transfections. Because it is a microtechnique, only small amounts of DNA, cells and transfection reagents are necessary, and it is easy to handle multiple DNA transfections or cotransfections in different cell lines and in duplicates or triplicates. The technique can be used to study viral gene expression, virus replication and chloramphenicol acetyltransferase (CAT) assay in different cell lines, for example, in the large scale screening and testing of antiviral agents.

Animals↗
PubMed1991

Oka/Merck varicella vaccine in healthy children: final report of a 2-year efficacy study and 7-year follow-up studies.

A large double-blind, randomized, placebo-controlled trial of live attenuated Oka/Merck varicella vaccine was conducted among healthy children, 1-14 years of age. During the first varicella season, the efficacy of the vaccine among susceptible children was 100%1. During the second varicella season, 22 children were diagnosed with varicella; 21 cases in placebo recipients and one in a vaccine recipient. The overall efficacy of the vaccine through two varicella seasons was 98%. After the code for the study was broken, the original group of vaccine recipients continued to be followed for development of varicella. The estimated proportion of vaccine recipients who remained varicella-free at the end of 7 years was 95%. The 23 cases of varicella that occurred in vaccine recipients over the 7-year period were considerably milder than natural varicella. The average number of lesions was 53, 50% of the children had non-vesicular rashes, and 14% of the children had a temperature greater than or equal to 38.9 degrees C (102 degrees F), oral. The persistence of antibody in a subset of vaccine recipients followed for 6 years was 100%.

Adolescent↗
PubMed1991

Comparison of acellular and whole-cell pertussis-component diphtheria-tetanus-pertussis vaccines in infants. The APDT Vaccine Study Group.

In a multicenter, double-blind, randomized, longitudinal study, 252 children received licensed Lederle diphtheria-tetanus toxoids and pertussis vaccine adsorbed (DTP) at 2, 4, and 6 months of age, and 245 children received a DTP vaccine with the Lederle/Takeda acellular pertussis component (APDT) at the same ages. Both groups of children received APDT vaccine at 18 months of age. After each of the first three immunizations, APDT vaccine recipients had fewer local and systemic reactions than did DTP vaccinees. Reactions after the 18-month APDT vaccination were minimal in severity regardless of the vaccine previously received. Antibody responses to lymphocytosis-promoting factor and agglutinogens were more pronounced in DTP recipients; however, APDT recipients had a better serologic response to filamentous hemagglutinin, and responses to the 69K protein were equivalent. This APDT vaccine produces fewer reactions than the standard whole-cell DTP vaccine. The protective significance of the serologic responses to the APDT vaccine is unknown, but the greater response to filamentous hemagglutinin and equivalent response to the 69K protein compared with those to DTP vaccine seem promising.

Agglutination Tests↗