Search PubMed⌕ Search

Biomedical subjects

R Edelman

Publications and source records attributed to R Edelman.

At least 91 records · Page 5Linked to original sources
PubMed1992

Efficacy of bovine milk immunoglobulin concentrate in preventing illness after Shigella flexneri challenge.

The protective efficacy of oral bovine immunoglobulin concentrates derived from colostrum against challenge with Shigella flexneri was studied in healthy adult volunteers in a randomized, double-blind fashion. Volunteers were given a product consisting of hyperimmune immunoglobulin concentrate with a high titer of anti-S. flexneri 2a lipopolysaccharide (LPS) with sodium bicarbonate or a control preparation with sodium bicarbonate three times a day for seven days. On the third day of treatment, volunteers received a challenge of 10(3) colony-forming units of S. flexneri 2a strain 2457T. None of the volunteers who received the high-titered hyperimmune product became ill, compared with 45% of volunteers who received the placebo (P less than 0.05). The duration of shedding of the challenge organism was decreased, and the active immune responses to S. flexneri LPS were less frequent and of lower magnitude in volunteers given the immunoglobulin concentrate than in those in the control group. High-titered, orally administered bovine immunoglobulin concentrate protects against shigellosis and may be useful in preventing shigellosis among travelers, military personnel, and individuals at risk during a Shigella outbreak.

Animals↗
PubMed1991

Perspective on the development of vaccines against Lyme disease.

Lyme disease, the multisystem illness caused by the tick-borne spirochaete, Borrelia burgdorferi, has emerged as a threat to public health worldwide. It is a particularly vexing problem in the United States where it is growing in range and intensity. In fact, in some hyperendemic regions of New York and New England, Lyme disease is now such a threat that it interferes with all sorts of outdoor activities, and has even led to depreciation of real estate values. Family dogs in these areas seem to have been particularly hard hit by a near epidemic of lameness caused by Lyme arthritis. Persons at high risk for infection, such as outdoor workers, campers and hikers, suburbanites with lawns to cut, and pregnant women exposed to potentially infected Ixodes ticks, are clamouring for some means of protection beyond simple behaviour modification and tick avoidance which are known not always to work. Hence, the interest in human and veterinary vaccines against Lyme disease is growing.

Antibodies, Bacterial↗
PubMed1991

Cytotoxic CD4+ T cells from a sporozoite-immunized volunteer recognize the Plasmodium falciparum CS protein.

The present data provide the first evidence that a protozoan parasite, Plasmodium falciparum, can induce CD4+ cytotoxic T cells in man. The CD4+ cytotoxic T lymphocytes (CTL) were derived from a sporozoite-immunized volunteer who was protected against challenge with P. falciparum sporozoites. These T cells recognize an epitope within the circumsporozoite (CS) protein, an immunodominant sporozoite surface antigen, present also in liver stages of the parasite, which has been investigated as a vaccine candidate. The class II restricted T cell clones specifically lyse autologous B cells pulsed with a synthetic peptide representing a C-terminal sequence of the P. falciparum CS protein. The same peptide, as well as recombinant or native CS protein, also stimulates proliferation and gamma-interferon production by the CD4+ CTL. The CTL epitope, KIQNSLSTEW, is recognized in the context of HLA-DR7 and overlaps both a highly conserved, as well as a polymorphic, region of the P. falciparum CS protein.

Adult↗
PubMed1991

Safety and immunogenicity of a recombinant sporozoite malaria vaccine against Plasmodium vivax.

A recombinant Plasmodium vivax circumsporozoite (CS) antigen representing approximately 70% of the CS protein was expressed in yeast and adsorbed onto aluminum hydroxide for use as a malaria vaccine. In a study of safety and immunogenicity, 30 volunteers were divided into four groups of 5, 5, 10, and 10 individuals, and inoculated intramuscularly with 50, 100, 200, or 400 micrograms of vaccine, respectively. Primary vaccinations were followed by two booster immunizations at six weeks and six months. Overall, the vaccine was well tolerated. Following the third vaccination, one volunteer developed acute hepatitis of uncertain etiology that resolved without sequelae. All volunteers in the 400-micrograms group, and six of 10 in the 200-micrograms group generated IgG against P. vivax CS protein, as determined by Western blot using recombinant CS protein. However, the magnitude of the antibody response measured by indirect immunofluorescence of intact sporozoites or enzyme-linked immunosorbent assay against the recombinant protein was low, and responses could not be boosted. Antigen-driven replication studies using peripheral blood lymphocytes failed to detect proliferative responses specific to peptide sequences represented in the recombinant vaccine, except in one volunteer. Minimal humoral and cell-mediated immune responses developed in most recipients who received this recombinant CS vaccine.

Adult↗
PubMed1991

Enteric vaccines.

Considerable progress has been made in the past decade in developing vaccines against the most important bacterial and viral infections of the gastrointestinal tract. Members of the Division of Geographic Medicine in the Center for Vaccine Development have played a prominent role in the laboratory development and clinical testing of these vaccines. A new oral typhoid vaccine, Ty21a, has been licensed in the United States. A genetically engineered live oral cholera vaccine developed in the CVD is undergoing clinical trials in cholera-endemic areas. Multiple vaccine candidates against Shigella, enterotoxigenic E. coli, and rotavirus are in clinical trial in the United States or overseas. Rapid advances in molecular biology, together with new knowledge of mucosal and cellular immunity, will produce more vaccine candidates in the future. The CVD intends to be in the forefront of these developments.

Bacterial Infections↗
PubMed1990

Indications for selective coupling to phosphoinositide hydrolysis or to adenylate cyclase inhibition by endogenous muscarinic receptor subtypes M3 and M4 but not by M2 in tumor cell lines.

The muscarinic receptor subtype mRNAs expressed in cell lines were determined by Northern blot analysis. The biochemical responses of the muscarinic receptors in these cell lines (phosphoinositide hydrolysis and cAMP levels) were studied and correlated to the corresponding muscarinic receptor subtype as determined by mRNA expression. PC12 cells that expressed M4 subtype mRNA exhibited muscarinically dependent adenylate cyclase inhibition, whereas C6 and SK-N-SH cells expressing M3 subtype mRNA exhibited muscarinically dependent phosphoinositide hydrolysis. IMR-32 cells (M2 subtype mRNA) exhibited both muscarinically dependent phosphoinositide hydrolysis and adenylate cyclase inhibition. These results suggest that endogenous M3 and M4 receptor subtypes are selectively coupled to phosphoinositide hydrolysis and adenylate cyclase inhibition, respectively, whereas the M2 receptor subtype is coupled to both responses.

Adenylyl Cyclases↗
PubMed1990

Adjuvants.

In summary, HIV vaccine studies described have generally not been designed to measure the effect of the adjuvant or to make comparisons between adjuvants. In only one study was a head-to-head comparison made between HIV antigen alone and antigen formulated with different adjuvants. We hope that future experiments with HIV/SIV vaccine candidates will be designed to determine the relative potency and safety of different adjuvants. Unfortunately, such experiments tend to be tedious and expensive. The design of these studies will need to address a number of variables which influence the response to the vaccine, including route and schedule of immunization, genotype and species of the vaccinated subject, and intrinsic characteristics of the antigen. In addition, the immunologic endpoints should include measurement of both B and T cell function. The carrier/adjuvant/antigen formulation should be hand-tailored and then standardized so that it is manufactured reproducibly without producing different biological effects between lots, and the vaccine formulation should be stable on storage and shipping. Finally, we obviously need to identify and test the protective antigen or antigens. The best adjuvant will never correct the choice of the wrong epitope.

AIDS Vaccines↗
PubMed1990

Future vaccines against enteric pathogens.

A small number of bacterial agents, including enterotoxigenic Escherichia coli (ETEC), enteropathogenic E. coli (EPEC), Shigella and Vibrio cholerae 01 and one virus, rotavirus, combine to cause a major proportion of the diarrheal illness of public health importance worldwide. Salmonella typhi is by far the major cause of enteric fever. Attempts to develop safe, practical, and effective vaccines against these agents are under way. Examples of vaccine candidates include live oral vaccines against S. typhi, V. cholerae, Shigella, and rotavirus, and inactivated, submit vaccines given parentally or orally against S. typhi, V. cholerae or ETEC. Although the oral attenuated S. typhi vaccine is ready for commercial license, it will be several years before the other vaccines are proven to be practically safe and effective in children and adults.

Bacterial Vaccines↗
PubMed1989

Immunity to rotaviruses.

A potent, multivalent, serotype-specific RV vaccine and improved tests for measuring vaccine potency would help eliminate the necessity to pretest for vaccine efficacy in every country selected for its deployment. Until then, the need will continue for vaccine trials in various countries because the pathogenesis and epidemiology of RV and RV serotypes differ between and within countries. Although RV vaccinology is complex, it has forged ahead of our knowledge of RV immunopathogenesis and epidemiology.

Animals↗
PubMed1988

Two sequential outbreaks of rotavirus gastroenteritis: evidence for symptomatic and asymptomatic reinfections.

In two sequential outbreaks of rotavirus gastroenteritis that occurred in a kibbutz in southern Israel (the Negev), 32 persons (9% of the population) were ill in the first and 45 (13% of the population) in the second. Excretion of virus, changes in titers of rotavirus-specific serum IgG, or both implicated rotavirus in 72% of the illnesses in outbreak 1 and in 56% of the illnesses in outbreak 2. In both outbreaks the age-specific morbidity rate decreased with increasing age. Half (six of 12) of the children six to 27 months of age who were ill with rotavirus in outbreak 1 were ill with rotavirus again in outbreak 2, whereas two were asymptomatically infected; older children who were ill in outbreak 1 were not ill in outbreak 2. Serotype determination by enzyme-linked immunosorbent assay using monoclonal antibodies to VP7 implicated a serotype 3 virus in outbreak 1 and a serotype 1 virus in outbreak 2.

Adolescent↗
PubMed1987

Lyme disease ecology in Wisconsin: distribution and host preferences of Ixodes dammini, and prevalence of antibody to Borrelia burgdorferi in small mammals.

Lyme disease recently has been recognized in Wisconsin. Trapping studies were conducted at four geographically separate and ecologically distinct regions in Wisconsin to elucidate the distribution and host preferences of Ixodes dammini on small and medium sized mammals, and the occurrence of antibodies to Borrelia burgdorferi in these wild mammals. Peak I. dammini larval activity occurred from June-September. Nymphs were most active from May-August. White-footed mice (Peromyscus leucopus) and chipmunks (Tamias striatus) were important hosts for immature ticks. Mean numbers of I. dammini per mouse were highest in regions of high prevalence of Lyme disease. Antibody to B. burgdorferi was detected in sera of 60/371 (16%) white-footed mice, 5/104 (5%) chipmunks, 3/5 (60%) gray squirrels (Sciurus carolinensis), 0/8 raccoons (procyon lotor), and 0/12 opossum (Didelphis virginiana); antibody prevalence correlated positively with I. dammini occurrence, and seropositive animals were not detected in areas where I. dammini were not found. Two of 15 recaptured P. leucopus had greater than or equal to 4-fold changes in antibody titer. B. burgdorferi was cultured from blood of a P. leucopus captured in west-central Wisconsin, and was observed by direct immunofluorescence in 9/23 (39%) I. dammini nymphs. In Wisconsin, I. dammini has increased in numbers and has significantly expanded its range since its first recognition in 1968.

Animals↗