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Biomedical subjects

Robert Edelman

Publications and source records attributed to Robert Edelman.

At least 19 recordsLinked to original sources
PubMed2006

Bordetella Pertussis infections in vaccinated and unvaccinated adolescents and adults, as assessed in a national prospective randomized Acellular Pertussis Vaccine Trial (APERT).

BACKGROUND: Acellular pertussis (aP) booster immunizations have been recommended for adolescents and older persons to enhance long-term protection and to possibly reduce community transmission of infections. METHODS: This was a multicenter, randomized, double-blind vaccine trial in which one-half of the subjects received aP vaccine and one-half received hepatitis A vaccine (control subjects). All subjects were observed for almost 2 years for cough illnesses, and all underwent microbiologic and serologic studies for detection of pertussis infection. Immunoglobulin G (IgG) and immunoglobulin A (IgA) antibodies to pertussis toxin, filamentous hemagglutinin, pertactin, and fimbriae 2/3 were measured by enzyme-linked immunosorbent assay in serum samples obtained 1 and 12 months after immunization. Infection rates were determined with a variety of serologic criteria for control and vaccinated subjects. The incidence of prolonged cough illness was ascertained for subjects with and subjects without serologic evidence of infection. RESULTS: Infection rates among control subjects are particularly representative of those in nonimmunized adults. Among control subjects, 0.4%-2.7% had increases in pertussis antibody of various types and degrees over 1 year, and 20%-46% had prolonged cough illnesses during this interval. Pertussis toxin antibody had the greatest specificity for detecting increases in antibody levels. Asymptomatic infections were approximately 5 times more common than clinical illnesses that met a strict clinical and microbiologic case definition. Relative to control subjects, aP-immunized subjects may have fewer increases in the antibody level (i.e., infections), especially for antibodies to fimbriae 2/3 (an antigen not in the vaccine). CONCLUSIONS: Pertussis infections in older persons are largely asymptomatic. aP boosters confer protection for adolescents and adults against symptomatic pertussis and likely confer protection against mild and asymptomatic infections, and use of boosters may reduce transmission to others, especially infants.

Adolescent↗
PubMed2005

An unexpected cause of angina detected by ECG-gated cardiac computed tomography.

Until recently anomalous coronary artery anatomy was only identified either by coronary angiography, at autopsy, or during cardiac surgery. With recent developments in the area of cardiac imaging, ECG-gated cardiac computed tomography (CT) has emerged as a minimally invasive modality to delineate both coronary anatomy and pathology. We present a case of an anomalous right coronary artery origin from the ascending aorta detected by ECG-gated cardiac CT in a 47 year-old male who presented to the emergency department complaining of acute chest pain after intense exercise. Given its relatively non invasive nature, ECG-gated cardiac CT may assist in the diagnosis and management of patients with atypical chest pain in which more invasive diagnostic examinations (i.e. coronary angiography) are not warranted.

Angina Pectoris↗
PubMed2005

Restoration of immunity in lymphopenic individuals with cancer by vaccination and adoptive T-cell transfer.

Immunodeficiency is a barrier to successful vaccination in individuals with cancer and chronic infection. We performed a randomized phase 1/2 study in lymphopenic individuals after high-dose chemotherapy and autologous hematopoietic stem cell transplantation for myeloma. Combination immunotherapy consisting of a single early post-transplant infusion of in vivo vaccine-primed and ex vivo costimulated autologous T cells followed by post-transplant booster immunizations improved the severe immunodeficiency associated with high-dose chemotherapy and led to the induction of clinically relevant immunity in adults within a month after transplantation. Immune assays showed accelerated restoration of CD4 T-cell numbers and function. Early T-cell infusions also resulted in significantly improved T-cell proliferation in response to antigens that were not contained in the vaccine, as assessed by responses to staphylococcal enterotoxin B and cytomegalovirus antigens (P < 0.05). In the setting of lymphopenia, combined vaccine therapy and adoptive T-cell transfer fosters the development of enhanced memory T-cell responses.

Adoptive Transfer↗
PubMed2005

Efficacy of an acellular pertussis vaccine among adolescents and adults.

BACKGROUND: Pertussis immunization of adults may be necessary to improve the control of a rising burden of disease and infection. This trial of an acellular pertussis vaccine among adolescents and adults evaluated the incidence of pertussis, vaccine safety, immunogenicity, and protective efficacy. METHODS: Bordetella pertussis infections and illnesses were prospectively assessed in 2781 healthy subjects between the ages of 15 and 65 years who were enrolled in a national multicenter, randomized, double-blind trial of an acellular pertussis vaccine. Subjects received either a dose of a tricomponent acellular pertussis vaccine or a hepatitis A vaccine (control) and were monitored for 2.5 years for illnesses with cough that lasted for more than 5 days. Each illness was evaluated with use of a nasopharyngeal aspirate for culture and polymerase-chain-reaction assay, and serum samples from patients in both acute and convalescent stages of illness were analyzed for changes in antibodies to nine B. pertussis antigens. RESULTS: Of the 2781 subjects, 1391 received the acellular pertussis vaccine and 1390 received the control vaccine. The groups had similar ages and demographic characteristics, and the median duration of follow-up was 22 months. The acellular pertussis vaccine was safe and immunogenic. There were 2672 prolonged illnesses with cough, but the incidence of this nonspecific outcome did not vary between the groups, even when stratified according to age, season, and duration of cough. On the basis of the primary pertussis case definition, vaccine protection was 92 percent (95 percent confidence interval, 32 to 99 percent). Among unimmunized controls with illness, 0.7 percent to 5.7 percent had B. pertussis infection, and the percentage increased with the duration of cough. On the basis of other case definitions, the incidence of pertussis in the controls ranged from 370 to 450 cases per 100,000 person-years. CONCLUSIONS: The acellular pertussis vaccine was protective among adolescents and adults, and its routine use might reduce the overall disease burden and transmission to children.

Adolescent↗
PubMed2005

Phase 1 safety and pharmacokinetic study of chimeric murine-human monoclonal antibody c alpha Stx2 administered intravenously to healthy adult volunteers.

Hemolytic-uremic syndrome (HUS) is a serious complication of infection by Shiga toxin-producing Escherichia coli. Shiga toxin type 2 (Stx2) is responsible for the renal toxicity that can follow intestinal infection and hemorrhagic colitis due to E. coli. A chimeric mouse-human antibody, designated c alpha Stx2, that has neutralizing activity in a mouse model was produced and tested in healthy adult volunteers. In this phase I dose escalation study, c alpha Stx2 was generally well tolerated. Pharmacokinetic studies indicated that clearance was stable over the dose range of 1.0 to 10 mg/kg of body weight (0.249 +/- 0.023 ml/kg/h) but was higher for the 0.1-mg/kg dose (0.540 +/- 0.078 ml/kg/h), suggesting saturable elimination. A similar nonlinear trend was observed for the volume of distribution, where average values ranged from 0.064 +/- 0.015 liter/kg for the 1.0- to 10-mg/kg doses and 0.043 +/- 0.005 for the 0.01-mg/kg dose. The relatively small volume of distribution suggests that the antibody is limited to the vascular (plasma) compartment. The mean half-life was 165 +/- 66 h, with lowest values observed for the 0.1-mg/kg dose (56.2 +/- 9.7 h) and the highest values reported for the 10.0-mg/kg dose (206.4 +/- 12.4 h). Future studies are needed to confirm the safety of this c alpha Stx2, and innovative clinical trials will be required to measure its efficacy in preventing or treating HUS.

Adult↗
PubMed2004

Prevalence of antibody to Bordetella pertussis antigens in serum specimens obtained from 1793 adolescents and adults.

Serum specimens were obtained from all subjects in the adolescent and adult acellular pertussis (aP) vaccine efficacy trial before and after immunization to study the prevalence of IgG and IgA antibody and geometric mean titers to 4 Bordetella pertussis antigens. Of 1793 adolescents and adult subjects who received aP vaccine, only 20%, 68%, 59%, and 39% had concentrations of IgG antibodies to pertussis toxin, filamentous hemagglutinin, pertactin, and fimbriae types 2 and 3, respectively, that were greater than or equal to the limit of quantitation of the enzyme-linked immunosorbent assay used in the analysis. There was minimal variation in antibody prevalence with respect to geographic area, age, sex, or race.

Adolescent↗
PubMed2004

Immunogenicity of recombinant LT-B delivered orally to humans in transgenic corn.

Previous clinical studies have demonstrated the feasibility of using edible transgenic plants to deliver protective antigens as new oral vaccines. Transgenic corn is particularly attractive for this purpose since the recombinant antigen is stable and homogeneous, and corn can be formulated in several edible forms without destroying the cloned antigen. Transgenic corn expressing 1 mg of LT-B of Escherichia coli without buffer was fed to adult volunteers in three doses, each consisting of 2.1 g of plant material. Seven (78%) of nine volunteers developed rises in both serum IgG anti-LT and numbers of specific antibody secreting cells after vaccination. Four (44%) of nine volunteers also developed stool IgA. Transgenic plants represent a new vector for oral vaccine antigens.

Administration, Oral↗
PubMed2004

Immune responses and antibody decay after immunization of adolescents and adults with an acellular pertussis vaccine: the APERT Study.

As part of a prospective acellular pertussis (ACP) vaccine efficacy trial, 5 serum samples were obtained, over an 18-month period, from 101 ACP-vaccine recipients and 99 control subjects, to assess ACP antibody response and decay. Immunoglobulin (Ig) G and IgA antibodies to pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin (PRN), and fimbriae 2/3 (FIM) were measured by enzyme-linked immunosorbant assay, and titers of agglutinin were determined. Of the subjects, 16%-19% had preimmunization values of antibodies to PT that were above the assay's limit of quantitation (LOQ); in contrast, 36%-63% of the subjects had preimmunization values of antibodies to FHA, PRN, or FIM that were above the LOQ. Substantial increases in titers of IgG and IgA antibodies to the 3 ACP antigens (PT, FHA, and PRN) were observed. Over the 18-months, the percent decay in IgG and IgA antibodies ranged from 56% to 73% and from 57% to 70%, respectively; the IgG antibody response and decay suggests that geometric mean titers likely remain above the LOQ for 2-9 years and above the threshold of detection for 4-13 years. These findings support the use of ACP booster immunizations for adolescents and adults, to provide sustained levels of antibody.

Adolescent↗
PubMed2004

Quantitative Plasmodium sporozoite neutralization assay (TSNA).

The circumsporozoite (CS) protein is the major surface protein of Plasmodium sporozoites. Antibodies to the immunodominant repeat domain of CS immobilize sporozoites and prevent infection of hepatocytes. Plasmodium falciparum vaccines containing CS repeats are undergoing human trials in endemic areas, and proof of efficacy has been obtained. The correlates of protection are under investigation. Levels of anti-repeat antibodies in the serum of the human volunteers have been measured mostly by enzyme-linked immunosorbent assay (ELISA) and IFA. Assays that measure the effect of the serum antibodies on parasite infectivity (serum neutralization assays SNAs) are not usually performed because they require a susceptible host and P. falciparum sporozoites are highly infectious only to humans. To overcome this limitation, we developed a new assay named transgenic sporozoite neutralization assay (TSNA) that uses as neutralization target, a transgenic rodent malaria parasite Plasmodium berghei that bears the P. falciparum CS repeats [CS(Pf)]. Following incubation with human serum, CS(Pf) infectivity of HepG2 cells is evaluated by real-time PCR. We have compared ELISA titers and TSNAs in a limited number of sera from humans immunized with (T1B)4 MAP, a peptide vaccine containing P. falciparum CS repeats. A comparison between the two assays did not reach significance (p=0.175) when analyzed by non-parametric Spearman correlation method. Ongoing human trials of CS-based vaccines should provide an opportunity to determine whether TSNAs will provide better correlates of protective immunity than ELISA assays.

Animals↗
PubMed2003

Phase II safety and immunogenicity study of type F botulinum toxoid in adult volunteers.

An aluminum hydroxide (alum)-adsorbed, purified, botulinum F toxoid (Bot F) vaccine was manufactured to be administered as a stand-alone monovalent vaccine or to be added to the current botulinum pentavalent toxoid vaccine to make a hexavalent vaccine. We conducted a phase II trial of the Bot F vaccine over 3 years in 144 healthy adult volunteers to identify one of three vaccination schedules that was safe and maximally immunogenic for adult volunteers. We vaccinated 116 volunteers 1-3 times with Bot vaccine, and 28 volunteers 1-3 times with a licensed, alum-adsorbed hepatitis B vaccine (Engerix-B) as a reaction control group. After 1 year, 42 Bot volunteers with low, mouse anti-toxin titers (<0.10 IU/ml) received a booster injection and were followed for an additional year. The Bot vaccine inoculated three times over 28-42 days was generally well tolerated and safe, whether injected by the subcutaneous (s.c.) or intramuscular (i.m.) route, although it caused significantly more local reactions than did the HBV vaccine. Two vaccination schedules of three primary injections over 42 days (days 0, 14 and 42 or days 0, 21 and 42) provided significantly better protective immunity (anti-toxin levels >0.02 IU/ml) than did vaccinations given over 28 days (days 0, 7 and 28). Vaccine reactogenicity and immunogenicity were similar over 42 days whether administered subcutaneously or intramuscularly. However, even the most immunogenic schedule left 7-16% of volunteers unprotected at day 56 and 33-42% of vaccinees unprotected at 1 year. The booster dose administered at 1 year induced high levels of protective serum anti-toxin in all persons assayed which persisted for at least one additional year. A more potent vaccine formulation will be required to protect more individuals after primary immunization.

Adjuvants, Immunologic↗
PubMed2003

Does antigenic overload exist? The role of multiple immunizations in infants.

There is no evidence that currently recommended vaccines overload or weaken the infant immune system. Infants have an enormous capacity to respond safely and effectively to multiple vaccines. The schedule for the administration of childhood vaccines is tailored to the unique developmental pattern of the infant immune system. Childhood vaccines provide immediate protection from common childhood illness and establish the foundation for lifelong immunity that develops with subsequent vaccination or infection. Widespread vaccination of infants and children represents a public health triumph of the 20th century. This fact must be reinforced continually by health care workers and parent education to help maintain progress in the 21st century.

Adult↗
PubMed2003

Survey of human-use adjuvants.

Although there are only four adjuvants used in licensed vaccines for humans, a wealth of information on novel vaccine adjuvants has become available in both animal models and clinical studies over the past decade. Many vaccine candidates require immunopotentiation to achieve a satisfactory immune response, which is driving the search for new and safer approaches. In this review, we take a brief look at what is known of the mechanisms of action, consider some of the elements of product development, then survey several of the classes of adjuvants within the context of human trials.

Adjuvants, Immunologic↗
PubMed2003

Progress and controversy surrounding vaccines against Lyme disease.

Less than 20 years elapsed between the 1982 report of the identification and isolation of Borrelia burgdorferi and the licensure and marketing in the USA of a prophylactic vaccine against this pathogen. However, the manufacturer removed the vaccine from the market under 4 years after its release. The low demand undoubtedly was the result of limited efficacy, need for frequent boosters, the high price of the vaccine, exclusion of children, fear of vaccine-induced musculoskeletal symptoms and litigation surrounding the vaccine. Second-generation polyvalent outer surface protein (Osp)C vaccines may overcome some of these concerns but the precise antigenic components required for efficacy are uncertain. The development of the next generation of Lyme disease vaccines is in its infancy.

Animals↗
PubMed2003

Phase I trial of 16 formulations of a tetravalent live-attenuated dengue vaccine.

Laboratory-attenuated strains of each of the four dengue serotypes previously tested as monovalent vaccines in volunteers were combined and tested for immunogenicity, safety, and reactogenicity in 16 dosage combinations. Tetravalent vaccines made using combinations of high (10(5-6) plaque-forming units [PFU]/dose) or low (10(3.5-4.5) PFU/dose) dosage formulations of each of the four viruses were inoculated in 64 flavivirus non-immune adult volunteers to determine which, if any, formulation raised neutralizing antibodies in at least 75% of volunteers to at least three of four dengue serotypes following one or two inoculations. Such formulations, if safe and sufficiently non-reactogenic, would be considered for an expanded Phase II trial in the future. Formulations 1-15 were each inoculated into three or four volunteers (total = 54) on days 0 and 28. Formulation 16 was tested in 10 volunteers, five volunteers inoculated on days 0 and 30, one volunteer on days 0 and 120, and four volunteers on days 0, 30, and 120. Blood was drawn for serologic assays immediately before and one month after each vaccination, and for viremia assay on day 10 after each vaccination. The 16 formulations were safe, but variably reactogenic after the first vaccination, and nearly non-reactogenic after the second and third vaccinations. Reactogenicity was positively correlated with immunogenicity. Similar proportions of volunteers seroconverted to dengue-1 (69%), dengue-2 (78%), and dengue-3 (69%), but significantly fewer volunteers seroconverted to dengue-4 (38%). The geometric mean 50% plaque reduction neutralization test titers in persons who seroconverted were significantly higher to dengue-1 (1:94) than to dengue-2 (1:15), dengue-3 (1:10), and dengue-4 (1:2). Seven formulations met the serologic criteria required for an expanded trial, and three of these were sufficiently attenuated clinically to justify further testing.

Adolescent↗
PubMed2003

Vaccination of human volunteers with monovalent and tetravalent live-attenuated dengue vaccine candidates.

Four serotypes of monovalent live attenuated dengue virus vaccine candidates were tested for reactogenicity and immunogenicity in 49 flavivirus non-immune adult human volunteers. The four monovalent candidates were then combined into a tetravalent formulation and given to another 10 volunteers. Neutralizing antibody seroconversion rates after a single-dose monovalent vaccination ranged from 53% to 100%. Solicited reactogenicity was scored by each volunteer. A composite index, the Reactogenicity Index, was derived by these self-reported scores. Reactogenicity differed among the four serotype candidates with serotype-1 associated with the most vaccine related side effects. A second dose of monovalent vaccines at either 30 days or 90 days was much less reactogenic but did not significantly increase seroconversion rates. Seroconversion rates in the 10 volunteers who received a single dose of tetravalent vaccine ranged from 30% to 70% among the four serotypes. Similar to the monovalent vaccines, a second dose of the tetravalent vaccine at one month was less reactogenic and did not increase seroconversion. A third dose of the tetravalent vaccine at four months resulted in three of four volunteers with trivalent or tetravalent high-titer neutralizing antibody responses.

Adolescent↗
PubMed2002

Immediate-type hypersensitivity and other clinical reactions in volunteers immunized with a synthetic multi-antigen peptide vaccine (PfCS-MAP1NYU) against Plasmodium falciparum sporozoites.

We tested the clinical reactions to a synthetic, Plasmodium falciparum, circumsporozoite multiple antigen peptide (MAP) vaccine in 39 volunteers immunized two to three times over 2-8 months using a dose escalation design. Immediate pain at the injection site was associated with the adjuvant QS-21 (P<0.001), and delayed local inflammatory reactions were associated with high-titered circulating IgG anti-MAP antibody (P=0.03). Because two volunteers developed acute, systemic urticaria after the third immunization associated with development of serum IgE MAP antibody, we employed immediate-type hypersensitivity skin tests (ITH-STs) using intradermal injections of diluted MAP vaccine to identify persons sensitized to the vaccine. ITH-STs were negative in seven volunteers tested 27 days after the first vaccination, but six of these individuals developed positive wheal and flare reactions when tested 14 or 83 days after the second vaccination; IgE MAP antibody was detected in only one of them. Another cohort of 16 volunteers, including the 2 allergic individuals, were ITH-ST negative when first tested late after their second or third vaccination at 6-7 months. Five of five non-immunized persons were also ITH-ST negative. ITH-STs may help identify individuals sensitized to malaria peptides and at potential risk of developing systemic allergic reactions after re-vaccination.

Adjuvants, Immunologic↗