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Biomedical subjects

W R Ballou

Publications and source records attributed to W R Ballou.

88 records · Page 5Linked to original sources
PubMed1987

Plasmodium falciparum: elicitation by peptides and recombinant circumsporozoite proteins of circulating mouse antibodies inhibiting sporozoite invasion of hepatoma cells.

The immunodominant epitope region of the circumsporozoite protein of Plasmodium falciparum sporozoites contains 37 tandem repeats of the tetrapeptide Asn-Ala-Asn-Pro and 4 repeats of Asn-Val-Asp-Pro. Synthetic peptides and recombinant proteins of the repeat region were used to immunize mice using different doses and adjuvants. Antisera were tested for inhibition of sporozoite invasion of cultured human hepatoma cells. Synthetic peptides and recombinant proteins elicited high levels of antibodies that inhibited sporozoite invasion when emulsified with complete Freund's adjuvant. Since recombinant proteins with alum elicited a better antibody response to sporozoite invasion than they did without adjuvant, it may be that a recombinant protein containing 32 tandem copies of the tetrapeptide repeat combined with alum could be a candidate malarial vaccine suitable for human trials.

Animals↗
PubMed1986

Immunity to malaria and naturally acquired antibodies to the circumsporozoite protein of Plasmodium falciparum.

A candidate Plasmodium falciparum sporozoite vaccine, R32tet32, which includes 32 tetrapeptide repeats derived from the circumsporozoite protein of P. falciparum, has been developed on the basis of the hypothesis that antibodies to the repeat region of this protein will protect against sporozoite infection. The results of two in vitro assays, the circumsporozoite precipitation reaction and the inhibition of sporozoite invasion into hepatoma cells, are thought to indicate protective immunity. We therefore tested serum samples from persons living in a hyperendemic malarious area of Indonesia for antibodies against R32tet32 and for their ability to produce circumsporozoite precipitation and to inhibit sporozoite invasion of hepatoma cells. The prevalence and mean titer of antibody against R32tet32 increased with the age of the subjects, whereas the prevalence of P. falciparum infection in the community decreased. Only serum samples with IgG or IgM R32tet32 antibody titers greater than or equal to 1/800 had precipitation activity and invasion-inhibiting activity of more than 75 percent. When the serum samples were fractionated by affinity chromatography, only the fractions containing purified human antibody to R32tet32 were found to contain this activity. These data support the hypotheses that antibodies to the circumsporozoite protein are important in reducing the prevalence of malaria with increasing age among persons in areas in which malaria is endemic and that vaccine-elicited antibody to the circumsporozoite repeat region will protect against infection with P. falciparum sporozoites.

Adolescent↗
PubMed1986

Colonization of newly arrived house staff by virulent staphylococcal phage types endemic to a hospital environment.

The acquisition of hospital strains of Staphylococcus aureus by new house officers was studied in an 800-bed referral hospital over a 1-year period. S. aureus isolates, including three strains with characteristic phage patterns that had previously been documented to cause disease in patients and colonize hospital personnel, were recovered from the anterior nares of 35 of 54 newly arrived house officers. There was a significant correlation (r = 0.7475; P less than 0.02) between colonization with the dominant hospital strain (S) and exposure to the hospital environment over 12 months. No hospital-wide increase in infections owing to the S strain was seen during this period, which suggests that house staff acquired this strain from reservoirs within the hospital. The finding of colonization with virulent endemic S. aureus strains in house officers working on every ward of the hospital suggests that new strategies for control of S. aureus nosocomial infections must be considered and evaluated.

Bacteriophage Typing↗
PubMed1985

Expression of Plasmodium falciparum circumsporozoite proteins in Escherichia coli for potential use in a human malaria vaccine.

The circumsporozoite (CS) protein of the human malaria parasite Plasmodium falciparum may be the most promising target for the development of a malaria vaccine. In this study, proteins composed of 16, 32, or 48 tandem copies of a tetrapeptide repeating sequence found in the CS protein were efficiently expressed in the bacterium Escherichia coli. When injected into mice, these recombinant products resulted in the production of high titers of antibodies that reacted with the authentic CS protein on live sporozoites and blocked sporozoite invasion of human hepatoma cells in vitro. These CS protein derivatives are therefore candidates for a human malaria vaccine.

Animals↗
PubMed1985

Immunogenicity of synthetic peptides from circumsporozoite protein of Plasmodium falciparum.

In a study of recombinant proteins that might be useful in developing a vaccine against malaria, synthetic peptides from the circumsporozoite (CS) protein of Plasmodium falciparum were found to be immunogenic for mice and rabbits. Antibody to peptides from the repeating region of the CS protein recognized native CS protein and blocked sporozoite invasion of human hepatoma cells in vitro. Antibodies to peptides from regions I and II had no biologic activity, although antibody to region I recognized processed CS protein by Western blot analysis. These data support the feasibility of developing a vaccine against the sporozoite stage of the malaria parasite by using synthetic peptides of the repeating region of the CS protein conjugated to a carrier protein.

Amino Acid Sequence↗
PubMed1985

Frequent transmission of HTLV-III among spouses of patients with AIDS-related complex and AIDS.

Seven cases of acquired immunodeficiency syndrome (AIDS) and AIDS-related complex (ARC) associated with human T-cell leukemia (lymphotropic) virus (HTLV)-III infection were documented in married males whose family members consented to medical evaluation. Five spouses also had evidence of HTLV-III infection documented by isolation of virus and by detection of serum antibody directed against viral structural proteins. Three of the five HTLV-positive spouses also had clinical evidence of ARC. The remaining four spouses were clinically healthy. Eleven children (between 14 months and 13 years of age) were also evaluated for evidence of disease and exposure to HTLV-III. Only one 14-month-old child was seropositive for antibody to HTLV-III. These data support the opinion that close household contact to patients with ARC or AIDS is not an efficient mechanism for virus transmission, while demonstrating that HTLV-III can be transmitted by repeated heterosexual contact.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Rapid serodiagnosis of leptospirosis using the IgM-specific Dot-ELISA: comparison with the microscopic agglutination test.

The dot enzyme-linked immunosorbent assay (Dot-ELISA) was compared to the microscopic agglutination test (MA test) for the diagnosis of human leptospirosis. Of 177 sera from 68 soldiers who trained in the Republic of Panama, 102 sera were positive in the MA test and 93 of these sera were positive in the IgM-specific Dot-ELISA. Incidence of infection was 50 of 68 patients with the MA test and 48 of 68 in the IgM Dot-ELISA. Five MA test-positive sera were reactive only in the IgG-specific Dot-ELISA, suggesting previous exposure. All 21 infecting serovars of Leptospira interrogans, as determined by positive reactions in the MA test or culture of blood and urine specimens, were reactive in the Dot-ELISA. Of 75 sera negative in the MA test, 61 were nonreactive in the Dot-ELISA. However, 9 of these 14 Dot-ELISA-positive/MA test-negative sera were acute samples from patients whose later sera were MA test-positive. Positive reactions in the IgM Dot-ELISA occurred in 2 of 30 control, 4 of 10 Lyme disease, 1 of 11 relapsing fever, and 1 of 8 yaws sera; 10 syphilis patient sera were nonreactive. The IgM-specific Dot-ELISA appears to be sensitive and specific for the serodiagnosis of acute leptospirosis. In addition, this rapid test is inexpensive, simple to perform, utilizes minute volumes of killed leptospiral antigen and is easily adaptable to field use.

Agglutination Tests↗
PubMed1985

American cutaneous leishmaniasis: a comparison of three sodium stibogluconate treatment schedules.

Thirty-six patients with American cutaneous leishmaniasis were randomized to receive intravenous sodium stibogluconate for 10 days at a dose of 600 mg antimony (Sb) per day by one of three schedules: once daily by rapid infusion (A), by continuous 24 hr infusion (B), or in divided doses every eight hours by rapid infusion (C). Patients not cured after initial treatment were rerandomized to one of the other treatment schedules. An additional 19 patients who were not part of the randomized study received standard (STD) sodium stibogluconate treatment (600 mg Sb once daily by rapid infusion for 10 days, identical with schedule A). In the randomized study, the overall cure rate after the first course of treatment was 64%, but was higher for schedule A (100%) than for B (50%) or C (42%) (P less than 0.01). Considering all courses of treatment, schedule A was more effective (94%) than B (53%) or C (43%) (P less than 0.01). Paradoxically, patients in group A had a higher cure rate than patients in group STD (42% after the first course of treatment and 51% when all courses of treatment were considered). Side effects were mild and well tolerated. Total side effects were more frequent in groups B + C (52%) than A + STD (23%) due to an increased incidence of subjective complaints (26% vs. 10%, P less than 0.05) in patients receiving other than once daily rapid infusion. We conclude that giving the same total amount of sodium stibogluconate in three divided doses or by continuous infusion offers no advantage over standard, once daily treatment of American cutaneous leishmaniasis.

Antimony Sodium Gluconate↗
PubMed1984

Doxycycline therapy for leptospirosis.

To study antibiotic efficacy, 29 patients with leptospirosis were treated in a randomized, double-blinded fashion with doxycycline, 100 mg orally twice a day, or placebo. Therapy was given for 7 days in a hospital, and patients were followed for 3 weeks afterwards. Duration of illness before therapy and severity of illness were the same in both groups. Doxycycline reduced the duration of illness by 2 days and favorably affected fever, malaise, headache, and myalgias. Treatment prevented leptospiruria and had no adverse effects. Doxycycline is effective in therapy for patients with leptospirosis.

Double-Blind Method↗
PubMed1977

Testing for the Tay-Sachs gene in the Atlanta Jewish population.

In May 1975, three mass screening clinics for the asymptomatic Tay-Sachs carrier were held in Atlanta, Georgia. Ninety percent of the 2,330 adults screened were of Ashkenazi Jewish ancestry. One hundred seventy-six people were identified as possible carriers, 145 returned for retesting, and 74 were diagnosed as carriers. The Tay-Sachs heterozygote frequency estimated from this tested population was 0.043 or 1 in 23. Retesting of all possible carriers and assessment of their first-degree relatives were emphasized as saids in diagnosis of the carrier state. Our results indicated that the hexosaminidase A values in the white celll lysates used for the retest procedure provided a more reliable diagnosis of the carrier state than did enzyme values obtained from screening sera alone. Test results from first-degree relatives in all cases supported the assigned genotype of probands.

Europe↗
PubMedDate not supplied

Activity of human volunteer sera to candidate Plasmodium falciparum circumsporozoite protein vaccines in the inhibition of sporozoite invasion assay of human hepatoma cells and hepatocytes.

Sera from human volunteers immunized with either synthetic peptide (NANP)3-TT or recombinant protein R32tet32 Plasmodium falciparum CS vaccines were tested in the inhibition of sporozoite invasion (ISI) assays using human hepatoma (HepG2-A16) cells or primary human hepatocytes. Sera or purified immunoglobulin (Ig) from volunteers who were completely protected against P. falciparum sporozoite challenge had higher ISI activity than sera from non-protected volunteers, or the highest titre endemic serum. However, Ig from protected and non-protected volunteers did not block sporozoite invasion of human hepatocytes, suggesting that P. falciparum sporozoites invade hepatocytes by mechanisms which differ from those concerned with invasion of HepG2-A16 cells.

Animals↗
PubMedDate not supplied

Safety and immunogenicity of a Plasmodium falciparum sporozoite vaccine: boosting of antibody response in a population with prior natural exposure to malaria.

Recombinant sporozoite vaccine or placebo were administered once to 25 volunteers from an area endemic for malaria. Antibody to R32tet32 rose in 9 of 15 receiving vaccine and remained elevated in 6 for 6 months. Mean absorbance increase was 0.43 +/- 0.40 with vaccine, 0.01 +/- 0.23 with placebo, and 0.72 +/- 0.19 in responders. Six non-responders had significantly lower pre-immunization levels (0.07 +/- 0.05) than responders (0.39 +/- 0.25). There was an association between an increase in immunofluorescence (n = 4) and an increase in absorbance (n = 9) among vaccine recipients (n = 15). Vaccine-induced increase in antibody to natural circumsporozoite antigen was indicated by increases in immunofluorescence and by increases in circumsporozoite precipitation score in 2 of the 5 responders with highest antibody increase measured by enzyme-linked immunosorbent assay. Response to subunit sporozoite vaccine paralleled response to prior natural sporozoite exposure and was significant and prolonged in a population with prior natural exposure to malaria.

Adult↗
PubMedDate not supplied

Immunogenicity of Plasmodium falciparum circumsporozoite protein multiple antigen peptide vaccine formulated with different adjuvants.

Only low antibody levels were obtained from vaccinating human volunteers with single-chain peptide from the Plasmodium falciparum circumsporozoite protein (PfCSP). This resulted in modest protection against sporozoite challenge. In addition, HLA restriction limits the probability of synthesis of a vaccine effective for a diverse population. We report immunization studies with a multiple antigen peptide (MAP) system consisting of multiple copies of a B-cell epitope from the central repeat region of the PfCSP in combination with a universal T-cell epitope, the P2P30 portion of tetanus toxin. This MAP4(NANP)6P2P30 vaccine was highly immunogenic in four different strains of mice when used with various safe and nontoxic adjuvants. When this MAP vaccine was encapsulated in liposomes with lipid A and adsorbed to aluminium hydroxide and given three times at 4-week intervals, the resultant antibody prevented 100% of sporozoites from invading and developing into liver stage infection. This high degree of immunogenicity of MAP4(NANP)6P2P30 vaccine formulated in liposomes, lipid A and aluminum hydroxide provides the foundation for consideration of human trials with this formulation.

Adjuvants, Immunologic↗