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Biomedical subjects

G Schiffman

Publications and source records attributed to G Schiffman.

At least 37 records · Page 2Linked to original sources
PubMed1991

Zidovudine improves response to pneumococcal vaccine among persons with AIDS and AIDS-related complex.

Antibody responses to 23-valent pneumococcal vaccine were studied in 38 individuals infected with human immunodeficiency virus (HIV), including 6 with asymptomatic infection, 24 with AIDS or AIDS-related complex (ARC) receiving treatment with zidovudine, and 8 untreated AIDS/ARC patients. Antibody responses were significantly higher for asymptomatic persons (aggregate geometric mean, 972 ng of antibody nitrogen (AbN)/ml; P less than .001) and AIDS/ARC patients receiving a median of 12 weeks (range, 4-54) of zidovudine therapy (mean, 369 ng of AbN/ml; P less than .001) when compared with untreated AIDS/ARC patients. Antibody responses among zidovudine-treated AIDS/ARC patients were independent of the dose (mean, 629.2 mg/day; range, 100-1200 mg) or duration of zidovudine therapy. For zidovudine-treated AIDS/ARC patients, persistence of an aggregate antibody response 8 months after vaccination was associated with survival at 14 months after vaccination, whereas waning of response was not. Pneumococcal vaccine should be administered as early as possible in the course of HIV infection. Immunization should be delayed for at least 4 weeks for AIDS/ARC patients initiating zidovudine therapy.

AIDS-Related Complex↗
PubMed1990

Studies on Pneumococcus vaccine alone or mixed with DTP and on Pneumococcus type 6B and Haemophilus influenzae type b capsular polysaccharide-tetanus toxoid conjugates in two- to five-year-old children with sickle cell anemia.

Pneumococcus vaccine, injected alone or mixed with diphtheria-tetanus toxoid-pertussis, did not elicit significant concentrations of pneumococcus type 6 antibodies in 2- to 5-year-old sickle cell anemia patients (n = 22). Reinjection 5 months later failed to elicit a booster response to pneumococcus type 6. We then injected conjugates of pneumococcus type 6B and of Haemophilus influenzae type b (Hib), each bound to tetanus toxoid (TT), alternatively at monthly intervals into sickle cell anemia patients of the same age group (n = 25); most received 3 injections of each vaccine. Pneumococcus vaccine was administered to 19 patients and Hib to 1 at approximately 1 year of age. Blood samples were taken before each and approximately 6 months after the last injection. Infrequent and minimal local reactions and only 6 episodes of fever (3%) occurred after injection of the conjugates. Pneumococcus type 6B-TT elicited a rise in the geometric mean concentration of pneumococcus type 6 antibodies (Ab) from 104 ng of antibody nitrogen (AbN)/ml in preimmunization sera to 385 ng of AbN/ml after the first injection (P less than 0.01). There were further increases after the 2 subsequent injections; 6 months after the third injection, the mean concentration was 940 ng of AbN/ml and 15 of 16 (94%) had greater than 300 ng of AbN/ml. Hib-TT elicited a 160-fold increase of Hib antibodies to a geometric mean concentration of 39.0 micrograms of Ab/ml after the first injection. These levels rose approximately 2-fold following 2 additional injections to 71.7 micrograms/ml and declined to 10.7 micrograms/ml at the 6-month sampling.(ABSTRACT TRUNCATED AT 250 WORDS)

Anemia, Sickle Cell↗
PubMed1990

Increased risk of pneumococcal infections in cardiac transplant recipients.

We observed 5 episodes of pneumococcal infection among 129 cardiac transplant patients between March 1985 and December 1987, giving an estimated incidence of 36 cases per 1000 patient-years. Infections occurred a mean of 58 days after transplantation and included bacteremia with empyema, bacteremia alone, and pneumonia. All patients recovered from their infections. There was no correlation between infection and age, sex, immunosuppression, or rejection episodes. We also measured antibody levels to 12 pneumococcal antigens in 6 unvaccinated, uninfected patients before and after cardiac transplantation, to see if baseline antibody levels decreased. Protective levels of antibody were defined as greater than or equal to 300 ng of anticapsular antibody nitrogen per milliliter serum. Before transplantation patients had protective antibody levels to a mean of 8.7 +/- 1.2 pneumococcal serotypes; after transplantation, the number of presumably protective antibody levels decreased to 6.5 +/- 1.4 (P = 0.021). One of these patients subsequently developed pneumococcal pneumonia. Cardiac transplant patients are at increased risk of pneumococcal infections. Vaccinating transplant candidates prior to transplantation may provide protection after transplantation.

Adolescent↗
PubMed1990

Relationship between serum IgG2 concentrations and antibody responses to pneumococcal polysaccharides in children with chronic chest symptoms.

We measured IgG-class antibodies to 12 pneumococcal antigens pre- and post-immunization with polyvalent pneumococcal vaccine in 31 children who had experienced chronic chest symptoms. The purpose of the study was to determine the relation of IgG subclasses, especially IgG2, to the subjects' antibody responses to bacterial polysaccharide antigens, to see if measuring IgG subclasses would predict these responses. Twenty-nine children (90%) had low or low-normal levels of one or more IgG subclasses, including 20 out of 31 (65%) with low or low-normal levels of IgG2. Children studied had a relatively poor increase in levels of antibody to 10 of the 12 pneumococcal vaccine antigens investigated. Both pre- and post-immunization antibody levels were related to pre-immune serum concentrations of IgG2. Pre-immunization antibody levels were strongly related to post-immunization levels; when post-immunization antibody levels were adjusted for pre-immunization levels by partial correlation, the correlation between anticapsular antibody level post-immunization and IgG2 was no longer significant. Thus, in children with chronic chest symptoms, levels of antibody measured at a random interval after natural exposure to these bacterial polysaccharide antigens are related to levels of IgG2 subclass, but antibody increases after vaccination appear to be affected more by other factors.

Adolescent↗
PubMed1990

Serum antibody response in adult volunteers elicited by injection of Streptococcus pneumoniae type 12F polysaccharide alone or conjugated to diphtheria toxoid.

Conjugates of an uronic acid-containing capsular polysaccharide (CP), pneumococcous type 12F (Pn12F) bound to diphtheria toxoid (DT), were studied for safety and immunogenicity in adult volunteers. In mice, these conjugates, prepared with the same lot of DT and Pn12F-40234-006, a homogenous CP of high molecular weight, or Pn12-812408, a polydisperse CP with lower-molecular-weight material, were more immunogenic than the Pn12F alone and had T-cell dependent properties (A. Fattom, W. F. Vann, S.C. Szu, A. Sutton, X. Li, B. Bryla, G. Schiffman, J. B. Robbins, and R. Schneerson, Infect. Immun. 56:2292-2298, 1988). Adult volunteers, randomized into three groups, were injected either with one of these two conjugates or with Pnu-Imune, the 23 valent pneumococcus vaccine containing 25 micrograms of Pn12F as one of its components. Volunteers were injected two times, 4 weeks apart, with the Pn12F-DT conjugates and once with the Pnu-Imune. Side reactions following injection of the conjugates of Pnu-Imune were mild and short-lived. At 4 weeks and at 7 months after the first injection, higher levels of Pn12F antibodies were found in the volunteers injected with the conjugates than in the Pnu-Imune group (P less than 0.001). The conjugate prepared with the higher-molecular-weight Pn12F elicited higher levels of antibodies than the conjugate prepared with a lower-molecular-weight Pn12F preparation (P = 0.05). Both conjugates elicited about a 13-fold rise in DT antibodies.

Adolescent↗
PubMed1990

The effect of a bacterial vaccine on tumors and the immune response of ICR/Ha mice.

This study examined the effect of mixed bacterial vaccine (MBV), a biological response modifier prepared from Streptococcus pyogenes and Serratia marcescens, on the immune system of mice and on the regression of a transplantable mouse tumor sarcoma 37. The study examined MBV's biological properties and analyzed its chemical composition. The chemical composition varied with the growth media. A typical centrifuged, dialyzed supernate of the serum-containing preparation was found to consist mainly of protein and minimal amounts of carbohydrate and endotoxin, while MBV made with synthetic medium contained similar amounts of all three. MBV was nontoxic for mice, which gained weight following the injection of 0.5-1.0 ml of MBV. MBV caused regression of 20-100% of well-established mouse tumors without appreciable toxicity. MBV also had a striking effect on the immune response of mice to sheep red blood cells. When administered simultaneously with antigen injection, MBV increased the number of antibody-secreting splenocytes measured by the plaque-forming assay threefold. Serum antibody levels also increased two- to threefold. MBV did not enhance the immune response to pneumococcal polysaccharide type III, a B-cell-dependent response. However, the in vivo administration of MBV increased the in vitro response to MBV and the B-cell mitogen lipopolysaccharide. MBV compares favorably with other biological response modifiers because of its enhancing effect on the immune response and its oncolytic properties at nontoxic levels.

Animals↗
PubMed1989

Immune consequences of nonoperative treatment of splenic trauma in the rat model.

To investigate the immunologic consequences of non-operative management of splenic injury, three parameters were studied: survival following pneumococcal sepsis, clearance of blood-borne bacteria, following Hemophilus influenzae challenge, and antibody response to type III pneumococcal capsular polysaccharide. Two hundred twenty-five Sprague-Dawley rats were divided into three groups and subjected either to a splenectomy, a sham operation, or standard blunt trauma. A significant increase in mortality was noted in the splenectomized group as compared with both the traumatized and control groups when challenged with Streptococcus pneumoniae. In both the control and trauma groups, H influenzae cleared significantly within 18 hours. Blood-borne bacteria persisted at the same level for 72 hours in the splenectomized animals. Four and 11 days later, the antibody level in both traumatized and control groups was higher than in the splenectomized subjects (P less than .001). There was no difference in the serum antibody level between the control and trauma groups at four days. However, at 11 days the trauma group showed a significant decrease in the antibody level (P less than .05). It can be concluded that following spontaneously-healing splenic trauma in the rat model, survival, bacterial clearance, and antibody response were all superior to that observed in the splenectomized subjects. In addition, the healed splenic disruption did not impair clearance of blood-borne encapsulated bacteria.

Animals↗
PubMed1989

Response to pneumococcal vaccine among asymptomatic heterosexual partners of persons with AIDS and intravenous drug users infected with human immunodeficiency virus.

Antibody responses to pneumococcal vaccine were studied in asymptomatic heterosexual partners of persons with AIDS and intravenous drug users seropositive for human immunodeficiency virus (HIV). Serum antibodies to 12 pneumococcal capsular antigens were measured by radioimmunoassay. Eleven intravenous drug users seropositive for HIV, 13 seronegative intravenous drug users, and 10 each seropositive and seronegative sexual partners received 23-valent pneumococcal vaccine. Additional unvaccinated matched seropositives served as controls. Antibody responses were significantly lower among subjects seropositive for HIV (P less than .05). Fourteen (88%) of 16 seropositive subjects with baseline type-specific antibodies to one or more pneumococcal antigens less than 300 ng of antibody nitrogen/ml (ngAbN/ml) demonstrated a rise in one or more of these antibodies to greater than 400 ngAbN/ml. No clinical deterioration or decrease in T4 cells attributable to vaccination was found. Although antibody responses to pneumococcal vaccine among HIV-infected subjects were impaired, most with antibody levels less than 300 ngAbN/ml developed titers of one or more type-specific antibodies to levels greater than 400 ngAbN/ml without notable adverse effects.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Selective defect in the antibody response to Haemophilus influenzae type b in children with recurrent infections and normal serum IgG subclass levels.

We studied 15 children with recurrent infections and normal serum IgG, IgM, IgA, and IgG-subclass levels. After immunization, the geometric mean serum IgG antibody concentration to Haemophilus influenzae type b (Hib) was eightfold lower than that of age-matched control subjects (p = 0.002). The patients also had a lower geometric mean concentration of serum IgM and IgA directed to Hib, although these differences did not reach significance. However, the groups did not differ in their response to diphtheria toxoid and pneumococcal polysaccharides. To confirm these findings, an additional 11 patients were identified and immunized. The geometric mean serum IgG anti-Hib concentration for this group of patients was also significantly lower than of normal subjects (p = 0.004). We propose that the defect in the antibody response to Hib may be a marker for a poor antibody response to a variety of bacterial and viral antigens that results in an increased propensity to recurrent infections. The defect was not associated with IgG-subclass deficiency. The identification of children with selective antibody deficiency and recurrent infections is important for diagnostic and therapeutic reasons.

Adolescent↗
PubMed1988

Synthesis and physicochemical and immunological characterization of pneumococcus type 12F polysaccharide-diphtheria toxoid conjugates.

A scheme for the synthesis and purification of conjugates, composed of the type 12F capsular polysaccharide of Streptococcus pneumoniae (Pn12F) and diphtheria toxoid, is described. The scheme is a modification of that described previously for the Vi capsular polysaccharide of Salmonella typhi, a linear homopolymer of N-acetylgalactoseaminouronic acid (S. C. Szu, A. L. Stone, J. D. Robbins, R. Schneerson, and J. B. Robbins, J. Exp. Med. 166:1510-1524, 1986). Pn12F is a branched-chain copolymer composed of a hexasaccharide repeating unit containing an aminouronic acid, N-acetylmannoseaminouronic acid (K. Leontein, B. Lindberg, and J. Lonngren, Can. J. Chem. 59:2081-2085, 1981). Sulfhydryl groups were introduced into Pn12F by forming an amide bond between cystamine and carboxyl groups of N-acetylmannoseaminouronic acid in the presence of a carbodiimide. The disulfide moiety of cystamine was reduced to form the cysteamine derivative of Pn12F which was, in turn, covalently bound to diphtheria toxoid by using the heterobifunctional linker N-succinimidyl-3-(2-pyridylthio)propionate. Unbound, high-molecular-weight Pn12F was removed from the conjugate by hydrophobic interaction chromatography through octyl Sepharose by using n-octyl-beta-D-glucopyranoside as the eluent. In young outbred mice, Pn12F did not elicit detectable serum antibodies. Pn12F-diphtheria toxoid, in contrast, elicited antibodies after two injections and had T-cell-dependent properties as evidenced by a response to priming and by its ability to elicit booster responses. This scheme seems applicable to the synthesis of conjugates with other capsular polysaccharides containing aminouronic acids. Clinical evaluation of Pn12F-diphtheria toxoid conjugates in healthy and in immunocompromised hosts is planned.

Animals↗
PubMed1988

Analysis of humoral and phagocytic defenses against Streptococcus pneumoniae serotypes 1 and 3.

To better define relationships among pneumococcal anticapsular antibodies, opsonophagocytosis, and in vivo mouse protection, we measured these functions in sera from healthy individuals who had not received pneumococcal vaccine. For serotype 1 pneumococci, the level of antibody measured by radioimmunoassay did not predict mouse protection, as has been noted by others. For some sera, opsonic requirements for antibody and complement could be clearly demonstrated and a strong correlation obtained between concentration of antibody and degree of phagocytic killing. However, for most sera, antibody concentration did not correlate with opsonic activity, as measured by phagocytic bactericidal assay or uptake of radiolabeled bacteria. Sera with high concentrations of anticapsular antibody did not always support in vitro bacterial killing by leukocytes. Conversely, highly opsonic sera did not necessarily have substantial levels of measurable antibody. Moreover, in vitro opsonophagocytic activity failed to predict in vivo protection; sera could be opsonic in vitro but not protective in vivo and vice versa. For serotype 3 pneumococci, antibody concentrations correlated strongly with mouse protective titers, as has been noted by others for type 3. Opsonophagocytosis, as measured by leukocyte bactericidal activity, required both complement and heat-stable substance(s) present in high-antibody sera, presumably antibody. Furthermore, increasing concentrations of serum enhanced phagocytic killing in a fashion that could be correlated with anticapsular antibody content. However, correlation with opsonophagocytosis was not so strong as with mouse protection, and there was no correlation between antibody concentration and opsonization as measured by uptake of radiolabeled bacteria. These observations suggest that opsonophagocytosis (with the definitive end point of bacterial killing) cannot be the standard against which to measure antibody concentrations. Furthermore, host protective mechanisms against pneumococci remain to be clearly defined. Even if opsonization by anticapsular antibody is the primary mechanism, there is need for development of improved functional assays of protection.

Animals↗
PubMed1988

Minimal role for the spleen in antibody responses of C57BR/cdj mice to pneumococcal polysaccharide antigens.

The role of the spleen in antibody production and in susceptibility to pneumococcal infections remains poorly understood. Recently we showed that in A/J mice high antibody responses to polysaccharide antigens depend upon dosage, antigenic structure, interval between immunization and assay and the presence of the spleen. To investigate the possibility of alternative patterns of response, intact and splenectomized (Sx) C57BR/cdj mice were assayed for antibody responses to two structurally different pneumococcal polysaccharides, type 3 (SIII) and type 14 (SXIV). After 50 or 100 ng of SIII, intact C57BR/cdj mice produced uniformly low antibody responses that were further suppressed by splenectomy, but after 1,000 ng of SIII, C57BR/cdj mice, regardless of whether they were intact or Sx, produced antibody responses as high as those of intact A/J mice. Following SXIV, a spleen-dependent antigen, C57BR/cdj mice produced consistently lower antibody responses than A/J mice. Antibody responses to 500 or 5,000 ng of SXIV were totally obliterated in Sx C57BR/cdj mice; but unlike A/J mice, responses to 10,000 ng were similar regardless of whether C57BR/cdj mice were intact or Sx. The inability of intact C57BR/cdj mice to produce elevated responses to SIII or SXIV suggests that C57BR/cdj mice may lack the subset of spleen cells necessary for a vigorous response to these antigens. The data suggest that these mice could provide useful animal models for studying host variability in antibody responses to pneumococcal polysaccharides.

Animals↗
PubMed1987

Immunoglobulin G class and subclass antibodies to pneumococcal capsular polysaccharides.

Enzyme immunoassays were developed to measure immunoglobulin G (IgG) and IgG1-4 subclass antibodies to pneumococcal capsular polysaccharides (PCP) types 4 and 7F. In healthy subjects, anti-PCP antibodies were predominately of the IgG1 and IgG2 subclasses. There was a significant increase in IgG, IgG1, and IgG2 anti-PCP antibody concentrations following immunization with pneumococcal vaccine. IgG and IgG2, but not IgG1, anti-PCP antibody concentrations correlated with total anti-PCP antibody concentrations measured by the standard radioimmunoassay and with serum opsonic activity for serotype 7F Streptococcus pneumoniae. Such IgG and IgG subclass antigen-specific antibody assays may be useful to investigate the immune response to pneumococcal polysaccharides.

Adult↗
PubMed1987

Immune response of elderly adults to pneumococcus: variation by age, sex, and functional impairment.

The immune response of 271 elderly persons to the new 23-valent pneumococcal vaccine was studied prospectively. Sera were obtained prevaccination, at 1 month post- and 12 months postvaccination. They were analyzed by radioimmunoassay for the presence of antibody Types 1, 3, 6A, 7F, 8, and 9N. The results showed differences in antibody levels by sex of the individual (p less than .01 pre and p = .04 at 1 month post), with women having lower antibody levels than men. Women responded better to vaccination than men (p = .05), but they also lost their acquired antibodies faster (p less than .01). No age effect and no effect of level of functioning were observed within this group of elderly individuals. Participants who died had high initial levels and responded well. Major differences between the six types were noticed. Type 6A exhibited the described pattern most clearly, whereas Type 3 often behaved in an opposite pattern from the other five types. We conclude that sex differences persist even among elderly adults, that high levels of antibodies are not necessarily an indicator of good health, and that much unexplained variation between antibody types exist.

Aged↗
PubMed1987

Pneumococcal antibody levels one decade after immunization of healthy adults.

The authors investigated the persistence of anticapsular pneumococcal antibodies in 21 subjects one decade after administration of a single dose of a polyvalent pneumococcal polysaccharide vaccine. Fourteen vaccinees received a hexavalent vaccine composed of the polysaccharides of capsular types 1, 3, 4, 7F, 8, and 12F; four vaccinees received an octavalent vaccine consisting of these six polysaccharides and also those of capsular types 14 and 19F; and three vaccinees received a nonavalent vaccine that also included type 5 capsular polysaccharide. Antibody was measured by radioimmunoassay. The authors detected persistently elevated anticapsular antibody levels among more than one half of vaccinees who developed a significant rise in antibody 1 month following immunization one decade after administration of pneumococcal polysaccharide vaccine when these levels were compared to prevaccine levels for pneumococcal capsular types 4, 7F, and 8. This finding was not the case with pneumococcal types 1, 3, 12F, 14, and 19F; less than two fifths of vaccinees maintained increased levels of anticapsular antibody to these types one decade after administration of pneumococcal vaccine. Geometric mean anticapsular antibody levels for types 7F and 8 only were significantly higher one decade after vaccine administration compared with the levels before immunization (t-test, p less than 0.01).

Adult↗