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S Baqar

Publications and source records attributed to S Baqar.

36 records · Page 2Linked to original sources
PubMed1990

Lymphoproliferative responses to mitogens and HIV-1 envelope glycoprotein among volunteers vaccinated with recombinant gp160.

The protective immune response to human immunodeficiency virus type 1 (HIV-1) induced by vaccination will likely include cellular immune responses. We measured lymphoproliferative responses in persons vaccinated with a baculovirus-derived recombinant gp160 candidate AIDS vaccine. Twelve volunteers received either 40 micrograms of rgp160, 80 micrograms of rgp160, hepatitis B vaccine, or alum adjuvant alone on days 0, 30, and 180. Peripheral blood lymphocytes were collected on days 0, 28, 60, 120, 210, and 270 and were cryopreserved. Lymphocyte proliferation to mitogens and rgp160 with and without interleukin-2 stimulation were determined, and lymphokine production and antibody synthesis were measured. All vaccinees responded normally to stimulation with phytohemagglutinin and concanavalin A. One of 3 vaccinees who received 40 micrograms of rgp160, 2 of 2 vaccinees who received 80 micrograms of rgp160, and no controls developed rgp160-specific lymphoproliferative responses. No differences in the production of lymphokines (interleukin-2 and interferon-gamma) after stimulation with mitogens or rgp160 were found when rgp160 vaccinees and controls were compared. We conclude that rgp160 candidate vaccine induces antigen-specific lymphoproliferative responses in humans and does not interfere with immunocompetence as measured by in vitro responses to mitogen stimulation.

Concanavalin A↗
PubMed1990

Continuation of chloroquine-susceptible Plasmodium falciparum parasitemia in volunteers receiving chloroquine therapy.

Volunteers infected with a chloroquine-susceptible line of Plasmodium falciparum were administered standard oral chloroquine therapy at the first detection of parasites in the blood. Parasitemias progressed in the face of therapy for up to 5 days and to levels up to 100-fold greater than those at the initiation of treatment. Thereafter, infections cleared without a requirement for additional chemotherapy. This course of infection and response to treatment has not been previously reported and may have been detected because volunteers were exposed to an unusually large number of sporozoites. The observations are consistent with the hypothesis that prolonged parasitemia resulted from the continued release of merozoites from liver.

Administration, Oral↗
PubMed1990

Human studies with synthetic peptide sporozoite vaccine (NANP)3-TT and immunization with irradiated sporozoites.

The synthetic peptide Plasmodium falciparum circumsporozoite (CS) protein conjugate vaccine (NANP)3-TT was safe when given parenterally to 202 volunteers. However, with a few notable exceptions, antibody responses were low and could not be boosted. Vaccinees' lymphocytes did not proliferate when exposed in vitro to (NANP)3. The tetanus toxoid (TT) carrier immunomodulated the response to the CS peptide in that both epitopic suppression and immune enhancement were demonstrated during the course of the clinical trials. During efficacy challenge studies, 1 of 7 vaccinees was protected against sporozoite challenge and in other vaccinees the prepatent period was significantly delayed. P. falciparum-infected mosquitos were irradiated with 20,000 rad (200 Gy). Five volunteers were immunized with 54, 55, 224, 663, and 715 total infective bites of irradiated mosquitos in an attempt to immunize with attenuated sporozoites. Four of these volunteers had significant humoral and cellular immune responses. Two volunteers (who received the largest immunizing doses) were challenged by the bites of infective mosquitos and both developed parasitaemia. In the volunteer with the highest antibody titre there was a marked delay in patency as determined by serial plasmodial cultures. T-cell clones are being obtained and characterized.

Adult↗
PubMed1989

Evidence for a 6.5-day minimum exoerythrocytic cycle for Plasmodium falciparum in humans and confirmation that immunization with a synthetic peptide representative of a region of the circumsporozoite protein retards infection.

Immunization with a synthetic peptide which is representative of part of the repeating region of Plasmodium falciparum circumsporozoite protein resulted in an immunity which allowed vaccinees to retard the development of patent malaria as compared to nonimmunized controls. Analysis of infection dynamics showed that immunity could be attributed to either neutralization of about 92% of inoculated sporozoites, delayed development of the majority of parasites, or a combination of neutralization and delayed development. In spite of this impressive antiplasmodial capacity, all volunteers after being bitten by infected mosquitoes developed malaria, and seven of eight developed parasitemia between 6.5 and 7.0 days after infective mosquito bites.

Animals↗
PubMed1989

Estimate of Plasmodium falciparum sporozoite content of Anopheles stephensi used to challenge human volunteers.

Plasmodium falciparum infected Anopheles stephensi, taken from a group of mosquitoes which had been used to challenge recipients of (NANP)3-TT vaccine, were tested for P. falciparum sporozoite content by an immunoradiometric assay. Seventy-six percent were infected with mean and median sporozoite equivalents per mosquito of 220,994 and 217,398, respectively (SD = 54,911). This sporozoite density is greater than that usually found in the field. These data suggest that this challenge for evaluating P. falciparum sporozoite vaccines is a demanding test of immunity.

Animals↗
PubMed1989

Immunity to Salmonella typhi: considerations relevant to measurement of cellular immunity in typhoid-endemic regions.

Experiments were performed in Baltimore, Maryland and in Santiago, Chile, to determine the level of Salmonella typhi antigen-driven in vitro lymphocyte replication response which signifies specific acquired immunity to this bacterium and to determine the best method of data analysis and form of data presentation. Lymphocyte replication was measured as incorporation of 3H-thymidine into desoxyribonucleic acid. Data (ct/min/culture) were analyzed in raw form and following log transformation, by non-parametric and parametric statistical procedures. A preference was developed for log-transformed data and discriminant analysis. Discriminant analysis of log-transformed data revealed 3H-thymidine incorporation rates greater than 3,433 for particulate S. typhi, Ty2 antigen stimulated cultures signified acquired immunity at a sensitivity and specificity of 82.7; for soluble S. typhi O polysaccharide antigen-stimulated cultures, ct/min/culture values of greater than 1,237 signified immunity (sensitivity and specificity 70.5%).

Adolescent↗
PubMed1988

Stage-selective inhibition of rodent malaria by cyclosporine.

The relative susceptibility of different developmental stages of Plasmodium berghei to cyclosporine was investigated in vivo. Within 12 h of receiving a single 25-mg/kg (body weight) dose of cyclosporine, mice with patent P. berghei infections uniformly exhibited a rapid fall in asexual parasite stages. Initially, ring forms and mature schizonts disappeared. Subsequently, trophozoites disappeared between 21 and 24 h, whereas gametocytes persisted for 36 h. In contrast, when cyclosporine was administered to mice 1 day before inoculation (100 mg/kg) with P. berghei sporozoites and for 2 consecutive days after inoculation (25 mg/kg), infections developed normally. When mice with patent infections were placed on prolonged cyclosporine therapy (25 mg/kg per day), parasitemia initially disappeared but often recrudesced. Recrudescent parasites were frequently resistant to cyclosporine (Csr). The Csr phenotype remained stable after serial passage of parasites in mice and after transmission through Anopheles stephensi mosquitoes, in which the capacity to produce oocysts was reduced. When infections of untreated mice were initiated with equal numbers of Csr and cyclosporine-susceptible (Css) parasites and then carried through two serial cycles of mosquito-to-mouse transmission without cyclosporine treatment, the Csr phenotype was lost. The results indicate that cyclosporine selectively inhibits asexual blood stages of P. berghei and favors the emergence of Csr parasites with diminished infectivity for mosquitoes.

Animals↗
PubMed1988

A model for Plasmodium falciparum sporozoite challenge and very early therapy of parasitaemia for efficacy studies of sporozoite vaccines.

Plasmodium falciparum parasitaemias were induced in four non-immune volunteers by the bites of mosquitoes infected from cultured gametocytes. Radical cure was accomplished before three of the four volunteers developed clinical malaria. Despite very low peak levels of parasitaemia, the plasmodium was recultured from the blood of all volunteers. This volunteer model of early detection of parasitaemia and prompt treatment will contribute to the safe and practical efficacy testing of sporozoite vaccines, thus facilitating the selection of candidate vaccines for large scale definitive field trials.

Adult↗
PubMed1987

Safety, infectivity, immunogenicity, and in vivo stability of two attenuated auxotrophic mutant strains of Salmonella typhi, 541Ty and 543Ty, as live oral vaccines in humans.

Two Salmonella typhi mutants, 541Ty (Vi+) and 543Ty (Vi-), auxotrophic for p-aminobenzoate and adenine, were evaluated as live oral vaccines. 33 volunteers ingested single doses of 10(8), 10(9), or 10(10) vaccine organisms, while four others received two 2 X 10(9) organism doses 4 d apart. No adverse reactions were observed. Vaccine was recovered from coprocultures of 29 of 37 vaccinees (78%) and from duodenal string cultures of two; repeated blood cultures were negative. The humoral antibody response to S. typhi O, H, Vi, and lysate antigens in serum and intestinal fluid was meager. In contrast, all vaccinees manifested cell-mediated immune responses. After vaccination, 69% of vaccinees overall and 89% of recipients of doses greater than or equal to 10(9) responded to S. typhi particulate or purified O polysaccharide antigens in lymphocyte replication studies but not to antigens of other Salmonella or Escherichia coli. All individuals, postvaccination, demonstrated a significant plasma-dependent mononuclear cell inhibition of wild S. typhi.

Antibodies, Bacterial↗
PubMed1985

Transovarial transmission of murine typhus rickettsiae in Xenopsylla cheopis fleas.

It has been generally accepted that infected fleas do not pass on Rickettsia mooseri, or indeed any other known pathogen, to their progeny. It is reported here that such transovarial transmission does occur in laboratory-infected Xenopsylla cheopis fleas. By means of the direct fluorescent antibody test, Rickettsia mooseri was observed in cells of the hemolymph of infected fleas. As many as 11 percent of the adults and 2.9 percent of the larvae of the generation reared therefrom, had demonstrable rickettsiae. Moreover, batches of the F1 fleas were capable of transmitting the infection to more than 18 percent of the rats they infested. The data support the contention that Xenopsylla cheopis fleas play an important role in the maintenance of murine typhus in rats in nature.

Animals↗
PubMed1984

Genetic variation for West Nile virus susceptibility in Culex tritaeniorhynchus.

Mutant and geographical strains of Culex tritaeniorhynchus were compared for West Nile (WN) virus susceptibility by feeding on a high-titered blood-virus suspension. Eleven strains also were selected from 2-21 generations for an increase and/or a reduction of oral susceptibility using 90% and 10% infective virus doses, respectively. Only one of the 20 strains tested, e ma, was significantly less susceptible than the control strain. In the selection experiments, none of the strains showed a consistent decrease in susceptibility, but the Changa Manga II (CM) strain showed a sustained increase in susceptibility from generations F11-F21 when selection was discontinued. Reciprocal cross-matings and back-crosses were set up between the selected CM strain and two of the morphological mutant strains, e ma and re e ae, carrying homozygous recessive markers. The resulting progeny were tested for susceptibility to WN virus infection and the ability to replicate virus to high-titers after infection. These results suggest that the trait of increased susceptibility is dominant over resistance. The enhanced ability of infected mosquitoes to replicate WN virus showed partial dominance. Both of these traits appear to be polyfactorial, and are apparently associated with more than one chromosome in Cx. tritaeniorhynchus.

Animals↗
PubMed1982

West Nile virus in Pakistan. 1. Sero-epidemiological studies in Punjab Province.

Serum samples collected during 1978-79 from residents of the Chiniot and Changa Manga National Forest (CMF) areas of Punjab Province, Pakistan, had over-all neutralizing (N) antibody positive rates for West Nile (WN) virus of 32.8% (n = 192) and 38.5% (n = 239), respectively. Comparison of the age-specific antibody rates indicated that the pattern of exposure to infection was different in the two areas. Samples from a 1968 serosurvey of residents of the CMF area had an age-specific N antibody profile similar to the 1978 CMF sample, but both the over-all N and haemagglutination-inhibition (HI) antibody positive rates were much higher in the 1968 sample. When tested against antigen prepared from the Pakistan I-746 strain of WN virus, the percentage of sera HI antibody positive and the geometric mean titre of the sera were significantly higher than when tested against the Egypt-101 antigen. One of 124 and 11 of 50 sera from the 1978 and 1968 samples from CMF exhibited detectable HI antibody against dengue-3 virus, respectively, indicating cross-reacting flavivirus antibody was present. None of the positive sera had a higher titre against dengue-3 than against WN virus, but four of the 1968 sera reacted to equal titre against both antigens. During the 1978-79 CMF survey, serum samples from domestic and wild animals were tested for WN virus antibody. Of the 317 wild birds captured, 85 were N-antibody positive. The only frequently bled mammal was the Indian cow, from which 21 of 58 samples were positive for WN antibody.

Animals↗
PubMed1982

West Nile virus in Pakistan. III. Comparative vector capability of Culex tritaeniorhynchus and eight other species of mosquitoes.

Eight species of mosquitoes from Pakistan were compared with Culex tritaeniorhynchus as experimental vectors of West Nile (WN) virus. When fed by the membrane or cotton-pledget methods on a dose of WN virus 100% infective for Cx tritaeniorhynchus, 95% and 73% of the females of Cx fuscocephala and Cx pseudovishnui became infected, respectively. Cx quinquefasciatus, Cx univittatus, Aedes albopictus, Ae. caspius, Ae. indicus and Ae. lineatopennis were all significantly less susceptible than Cx tritaeniorhynchus. In agreement with the single dose comparisons, the median per os infective dose of WN virus for Cx fuscocephala, Cx pseudovishnui and Ae. caspius was substantially greater than for Cx tritaeniorhynchus. The median parenteral infective dose for all six species tested was less than 1 SMICLD50. Both Cx tritaeniorhynchus and Cx quinquefasciatus were more susceptible to infection with WN virus when fed on viraemic chickens than when fed on defibrinated blood using cotton pledgets or membranes. After infection by intrathoracic inoculation, only Ae. indicus and Ae. lineatopennis showed a reduced ability to transmit WN virus when compared to Cx tritaeniorhynchus.

Animals↗
PubMed1981

Dual infections of Culex tritaeniorhynchus with West Nile virus and Nosema algerae.

Culex tritaeniorhynchus females infected with the microsporidian Nosema algerae, and uninfected control females were compared for susceptibility to infection with West Nile (WN) virus and for the ability to transmit virus. When fed on a high titered dose fo virus, 95% of the control females became infected, whereas only 65% of the N. algerae-infected females were infected with WN virus. However, at two lower viral doses, no differences in susceptibility were observed. No significant differences in transmission ability were found between the N. algerae-infected and control females when tested at 10, 14, and 21 days after infection with WN virus. Also, in mosquitoes dually infected with N. algerae and WN virus, neither agent affected the ability of the other to replicate.

Animals↗
PubMed1979

Comparison of vector competence for West Nile virus of colonized populations of Culex tritaeniorhynchus from southern Asia and the Far East.

Seven colonized stocks of Cx. tritaeniorhynchus from different geographic areas of Southern Asia and the Far East were assayed for susceptibility to WN virus infection by membrane feeding and by intrathoracic inoculation. Infected females also were tested for their ability to transmit virus to baby mice. No geographic pattern of differential susceptibility to WN virus infection was apparent from the experiments; however, the per os ID50 of one strain from Khulna, Bangladesh was over 10-fold greater than the ID50's of stocks from Karachi, Pakistan and Sendai, Japan. No difference in susceptibility was found by parenteral inoculation of virus. Likewise, greater than or equal to 90% of infected females from all the colonies were able to transmit virus.

Animals↗
PubMedDate not supplied

Estimate of anti-Plasmodium falciparum sporozoite activity in humans vaccinated with synthetic circumsporozoite protein (NANP)3.

A mathematical model was defined to estimate the degree of in vivo activity against Plasmodium falciparum sporozoites expressed by volunteers vaccinated with a synthetic peptide comprising the immunodominant epitope of the circumsporozoite protein. Relative to the course of infection in non-immunized controls, infections in vaccinated volunteers corresponded to the neutralization or delay of development of greater than 99% of challenge sporozoites.

Animals↗
PubMedDate not supplied

Safety and immunogenicity in man of a synthetic peptide malaria vaccine against Plasmodium falciparum sporozoites.

A 12 amino-acid synthetic peptide (NANP)3 comprising the immunodominant epitope of Plasmodium falciparum circumsporozoite protein was conjugated to tetanus toxoid (TT), adjuvanted with aluminium hydroxide, and administered intramuscularly in three doses at monthly intervals to 35 healthy males as a malaria vaccine. No significant adverse reactions were noted, with mild soreness at the injection site the only common symptom. Seroconversions against NANP occurred in 53% and 71% of recipients of 100 or 160 micrograms, respectively, measured by enzyme-linked immunosorbent assay (ELISA). Most ELISA-positive sera reacted with sporozoites by indirect immunofluorescence (IFA). Three vaccinees with the highest ELISA and IFA titres and four unimmunized controls were challenged with P. falciparum sporozoites introduced via the bites of infective Anopheles mosquitoes. Blood stage parasites were detected in all controls by 10 days (mean 8.5 days, range 7-10). In contrast, the two vaccinees who became infected did not manifest parasitaemia until day 11 and the third vacinee showed neither parasites nor symptoms during the 29 day observation period. This first synthetic peptide parenteral vaccine against a communicable disease tested in man is safe and stimulates biologically active antibodies. These observations encourage the development of improved vaccine formulations which, by enhancing immunogenicity, may lead to practical vaccines to assist in the control of falciparum malaria.

Animals↗