Peak Antibody Levels Research Articles

Antigens recognized by the human immune response to vaccination with a bivalenthardjo/pomonaleptospiral vaccine

Serum from volunteer subjects vaccinated with a bivalent whole cell vaccine of Leptospira interrogans serovar hardjo/serovar pomona grown in protein-free medium, was tested by the microscopic agglutination test (MAT), enzyme-immunoassay (EIA) and immunoblotting. Specific IgM antibodies to either serovars hardjo or pomona were detected in some subjects as early as 6 days after vaccination with peak antibody levels occurring 13-68 days after vaccination. Whereas all subjects produced specific IgM to both serovars, not all produced specific IgG to both serovars. Immunoblotting with hardjo sonicate revealed that all subjects produced IgM antibodies reacting with the 15, 23 and 28 kDa components of hardjo lipopolysaccharide (LPS), and most produced IgM antibodies that reacted with the 34.5 kDa flagellar doublet. In contrast, not all sera immunoblotted against pomona sonicate reacted with the 29 and 35 kDa components of pomona LPS. However all subjects produced antibodies reacting with a diffuse 14.4-27 kDa band. These antibodies appeared early in the immune response. Serum from the one vaccinated subject tested protected hamsters from acute lethal infection with serovar pomona.

Antigens recognized by the human immune response to vaccination with a bivalent hardjo/pomona leptospiral vaccine

Serum from volunteer subjects vaccinated with a bivalent whole cell vaccine of Leptospira interrogans serovar hardjo/serovar pomona grown in protein-free medium, was tested by the microcospic agglutination test (MAT), enzyme-immunoassay and immunoblotting. Specific IgM antiboidies to either serevars hardjo or pomona were detected in some subjects as early as 6 days after vaccinated with peak antibody levels occurring 13–68 after vaccination. Whereas all subjects produced specific IgM to both serovars, not all produced specific IgG to both serovars, Immunoblotting with hardjo sonicate revealed that all subjects produced IgM antibodies reacting with the 15, 23 and 28 kDa components of hardjo lipopolysaccharide (LPS), and most produced IgM antibodies that reacted with the 34.5 kDa flagellar doublet. In contrast, not all sera immunoblotted against pomona sonicate reacted with the 29 and 35 kDa components of pomona LPS. However all subjects produced antibodies reacting with a diffuse 14.4–27 kDa band. These antibodies appeared early in the immune response. Serum from the one vaccinated subject tested protected hamsters from acute lethal infection with serovar pomona.

Induction of antibodies to a tumor-associated antigen by immunization with a whole melanoma cell vaccine.

Urinary-tumor-associated antigen (U-TAA) is a glycoprotein present in the urine of melanoma patients. Previous studies have addressed the role of U-TAA in immunoprognosis. The present investigation was undertaken to determine whether the administration of whole melanoma cell vaccine (MCV) could induce the formation of anti-(U-TAA) antibodies in melanoma patients. The subjects of this study were stage II and III melanoma patients receiving MCV alone or in conjunction with cyclophosphamide. Anti-(U-TAA) IgM and IgG antibody levels were determined by enzyme immunoassay in sequential serum samples from 15 stage II and III melanoma patients receiving MCV. U-TAA purified from the urine of a melanoma patient was used as a target in this assay. The mean anti-(U-TAA) IgM titer prior to vaccination was similar to that of a non-vaccinated melanoma control group (1:1138 +/- 214, n = 15 vs 1:1334 +/- 254, n = 7; P = 0.375) but prevaccination IgG levels were generally higher than in the control group (1:3984 +/- 602 vs 1:2595 +/- 423; 0.1 greater than P greater than 0.05). While only 6 of the 15 patients demonstrated a rise in levels of IgG antibodies (mean 1:2964 +/- 1047 pre-MCV to 1:9958 +/- 2677 post MCV, P less than 0.01), 11 of the 15 patients demonstrated a greater than twofold rise in their anti-(U-TAA) IgM titers following vaccination (1:1051 +/- 259 pre-MCV to 1:2518 +/- 576 post-MCV; P less than 0.005). In addition, patients with visceral metastases consistently elicited anti-(U-TAA) responses equivalent to those with more limited disease. Concomitant administration of cyclophosphamide did not affect the response rates of peak antibody levels. The possibility that these antibody responses were actually against histocompatibility locus antigens (HLA) (contaminating our U-TAA preparation) was ruled out because the target antigen (U-TAA) was devoid of HLA, and because the induction of anti-(U-TAA) antibodies did not correlate with the induction of anti-HLA antibodies. These results demonstrate augmentation of anti-(U-TAA) IgM and IgG antibodies by immunization with the MCV.

Detection of cow's milk protein intolerance by an enzyme-linked immunosorbent assay.

Circulating IgG antibodies to cow's milk proteins have been quantified in 182 children using an enzyme-linked immunosorbent assay (ELISA). Antibody levels in children with cow's milk protein intolerance (CMPI) were compared with those in control groups comprising other diarrhoeal diseases, atopic children, and a "normal" sample including children with toddler diarrhoea. Mean IgG antibody levels in children with CMPI were significantly higher than in any of the control groups. There were clear differences in peak antibody levels between CMPI and all other groups for each of the protein fractions tested. There was some overlap in titres between CMPI and other enteropathies but the assay gave 88% sensitivity and specificity for the diagnosis of CMPI overall and was 100% specific against the combination of non-enteropathic controls in this study. These findings indicate that the assay could be applied as an outpatient screening test for CMPI and would be particularly useful in differentiating "toddler" diarrhoea from CMPI.

Investigation of synthetic Escherichia coli heat-stable enterotoxin as an immunogen for swine and cattle.

In its native form Escherichia coli heat-stable enterotoxin (STa) is nonantigenic; however, neutralizing antibodies are elicited in animals vaccinated with toxin-carrier conjugates. To study the immunogenicity of STa, peptides STa1-18 and STa5-18 were synthesized, characterized, and conjugated to carrier proteins. Pregnant gilts and heifers were hyperimmunized with the respective conjugates. Following parturition neonates were challenged with virulent E. coli (K99+ STa+). Peptides coupled to ovalbumin and emulsified with Freund adjuvant elicited antibodies that neutralized toxin-induced fluid accumulation in suckling mice. Peptides coupled to particulate carriers, with or without muramyl dipeptide adjuvant, failed to induce a measurable response. Peak antibody levels in sera were observed following three doses of conjugate and persisted for several weeks. The serological response in cattle was superior to that observed in swine; however, antibody levels in porcine colostrum were higher than those observed in cattle. Clinical observations of neonates from vaccinated dams indicated that passively obtained antibody provided partial protection from disease, but not as complete as that demonstrable with whole cell bacterins that induce antibody to pili. However, the data suggest the potential for utility of synthetically prepared antigens.

HOME ADMINISTRATION OF IV IMMUNOGLOBULIN IS SAFE, EFFICACIOUS AND COST-EFFECTIVE.

Monthly infusions of intravenous immunoglobulin preparations have dramatically reduced morbidity in patients with humoral immunodeficiency. However, although peak antibody levels achieved with this therapy are adequate, low trough levels often occur before the next dose is due (leading …

Detection of serum antibodies and circulating antigens in a chimpanzee experimentally infected with Onchocerca volvulus

The course of the humoral immune response was followed in a chimpanzee experimentally infected over 27 weeks with a total of 168 Onchocerca volvulus 3rd-stage larvae obtained from naturally infected wild-caught blackflies. Antibodies against an adult worm extract could be detected by ELISA from week 16 onwards (after the inoculation of 44 larvae). Peak antibody levels were observed between weeks 66 and 74 (about one year after the last larval injection). Thereafter, antibody levels markedly decreased but rose again after week 120. First microfilariae could be detected from week 124 onwards. Microfilarial counts remained low (not more than two microfilariae per skin snip) until the end of the observation period. High levels of IgM antibodies against adult O. volvulus antigens were detectable between weeks 26 and 80 by ELISA. Total IgE levels were found to be only marginally elevated during the course of the infection. Circulating parasite antigens were only detectable for a short time (weeks 34 to 44) of the prepatent period by immuno-radiometric assays (IRMAs) using monoclonal antibodies which were raised against O. gibsoni eggs. Competitive radio-immuno-assays detected host antibodies inhibiting binding of 125I-labelled monoclonal antibodies to parasite antigens from week 28 onwards. Host antibodies clearly interfere later in infection with the detection of circulating antigens.

Immunity of sheep to homologous challenge with dog-borne Sarcocystis species following varying levels of prior exposure

Ford G. E. 1985. Immunity of sheep to homologous challenge with dog-borne Sarcocystis species following varying levels of prior exposure. International Journal for Parasitology 15: 629–634. Grazing sheep in which sarcocysts develop (sarcosporidiosis) survive the pre-cyst stages of the parasite infection which cause pathophysiological changes (sarcocystosis). A peak temperature rise occurs at 3–4 weeks post-infection in experimental animals. A maximum fall in packed cell volume occurs at 5–6 weeks post-infection. Groups of sheep maintained specific pathogen free were experimentally infected with sporocysts of dog-origin to determine the dose level required for protection or resistance, and 13 weeks later challenged with a pathogenic dose of 50,000 sporocysts. Prior exposure levels (PEL) were used of nil, 5, 50, 500 and 5000 sporocysts. All prior infections elicited an antibody response to a complement fixation test in all sheep. A peak antibody level was detected within 2 weeks of challenge, with a higher titre for all previously exposed groups than for the nil PEL controls. Resistance of the sheep to the challenge dose, based on reduction of counts of parasites developing (sarcosporidiosis), was shown by significantly lower counts for the 50 PEL group (85%), as well as for the 500 (92%) and 5000 PEL (98%) groups. The 5 PEL group was not resistant. The protection of sheep, based on reduction of the above pathophysiological changes (sarcocystosis), was highly correlated with the level of prior exposure ( r = −0.80, P < 0.001). The changes in body temperature and packed cell volume were significantly less in groups with 500 and 5000 PEL than with nil and 5 PEL. The 50 PEL group was intermediate.

Outcome of renal transplantation following a positive cross-match with historical sera: The ASHI survey

Analysis of retrospective data, obtained on 216 patients from 27 centers transplanted across some form of positive lymphocyte cross-match in a noncurrent serum, revealed that actuarial 1-yr graft survival was 69% in first transplants and 53% in recipients of second or subsequent transplants. Graft outcome did not correlate with peak antibody levels, change in antibody from peak to current, remoteness in time of the most recent positive serum, the number or timing of sera cross-matched, the technique or target cell cross-matched, or the degree of positivity of the most recent positive serum. Although a concurrent control population was not available, these results support the concept that acceptable graft survival can be achieved despite a positive cross-match with noncurrent sera.

Seasonal variation of in vitro lymphocyte proliferative response to ragweed antigen E

Seasonal variation of symptoms and IgE response to short ragweed (SRW) allergens is well documented. Clinical symptoms generally parallel the rise and fall of the SRW pollen count, whereas total and specific-IgE levels peak after the SRWpollen season with a more gradual return to preseason levels. Because IgE synthesis is under T-lymphocyte control, we tested for seasonal variation in T cell proliferative response to SRW antigen E (AgE) in vitro. Nine untreated SR W-sensitive and five nonallergic individuals were studied on 15 occasions from June 1981 through May 1982. In vitro proliferative index (SI) to AgE, serum total and specific IgE and SRWpollen counts were measured; all persons studied kept daily symptom diaries. The mean SI was higher for the atopic group on all 15 sampling dates. The cumulative SI and the daily SI were statistically different between groups before, during, and after pollination. The peak SI for the atopic patients occurred almost I 2 5 , wk after the pollination peak, and the peak IgE antibody levels to SRW occurred at 5 2 5 wk after the pollination peak. We conclude that in vitro responsiveness to AgE is a specific response of allergic individuals and that this response demonstrates a significant seasonal component.

Serological assays against Staphylococcus aureus peptidoglycan, crude staphylococcal antigen and staphylolysin in the diagnosis of serious S. aureus infections.

Immunoglobulin G antibody levels against Staphylococcus aureus peptidoglycan (PG) and crude staphylococcal antigen (SA) using enzyme-linked immunosorbent assay (ELISA) and antistaphylolysin (ASTA) antibody levels by gel diffusion were determined in 53 patients with S. aureus and 54 patients with non-S. aureus endocarditis and septicemia as compared with 63 febrile control patients. The two ELISAs were the most sensitive assays indicating S. aureus endocarditis in 83% and 88% in the PG- and SA-assays, respectively. 39% of non-S. aureus endocarditis patients were positive in the PG-assay due to antibodies cross-reacting with streptococci. A 100% specificity for S. aureus infections was obtained with the ASTA test, but this assay was less sensitive. A significant rise in anti-PG or anti-SA antibody levels was not only seen among S. aureus infections but also in some streptococcal and S. epidermidis infections as well as in 3 febrile control patients. When at least 2 of the 3 assays showed positive peak antibody levels 1-4 weeks after onset of infection together with a significant rise of both anti-PG and anti-SA antibody levels the S. aureus endocarditis diagnosis was highly suggestive. Thus, we recommend the combined use of these 3 assays using paired serum samples in diagnosing serious S. aureus infections.

Serum antibody responses of high-risk children and adults to vaccination with capsular polysaccharides of Streptococcus pneumoniae.

Pneumococcal antibody was measured in the sera of splenectomized children, children with neprotic syndrome, adult with chronic renal failure, adults maintained on hemodialysis, adult recipients of renal allografts, and normal children and adults before and after vaccination with a polyvalent vaccine against Streptococcus pneumoniae. The medical conditions of these patients are associated with increased morbidity and mortality due to pneumococcal disease. Nonimmunosuppressed splenectomized children, children with steroid-responsive nephrotic syndrome, and adults maintained on hemodialysis had normal concentrations of antibody in serum and normal antibody responses to pneumococcal vaccine. Children with steroid-resistant nephrotic syndrome and adult recipients of renal allografts had low concentrations of antibody in serum before and after vaccination but showed an antibody increase after vaccination. During the first year after vaccination of the splenectomized patients, serum antibody concentrations declined linearly by 24%-32% from the peak antibody level. These results suggest that immunization with pneumococcal polysaccharides may reduce the indicence of pneumococcal disease in some high-risk patients but not in others.

Temperature effects on ectotherm immune responses

Ectotherms are subjected to seasonal changes in temperature, a significant factor affecting their life processes and immune responses. Most teleost fishes, tropical anurans and reptiles can elicit immune responses over the entire range of their thermal tolerance limits. Their primary responses are temperature dependent with no apparent discrete temperature sensitive event. Temperature reductions from the species optima influence 1) response induction times, 2) levels of antibody produced, 3) times to reach peak antibody levels and to 4) reject allografts. Secondary or memory responses are temperature independent. These generalizations are also true for temperate amphibians and reptiles at non-hibernating temperatures. During hibernation however, primary and secondary responses cannot be elicited. This non-reactivity can be correlated with the decline in lymphocyte numbers and the thermal sensitivity of events occurring during the inductive and effector phases of immune responses.

Mechanisms of autoantibody production in autoimmune MRL mice.

The quantitative expression of anti-DNA and anti-Sm antibodies has been investigated in autoimmune MRL-lpr/lpr and MRL-+/+ mice. Anti-Sm antibodies were detected in sera from 21/23 lpr/lpr and 10/16 +/+ mice, with individual animals showing striking variation in the time-course and magnitude of this autoantibody response. The peak antibody levels of the responding animals of each substrain did not differ significantly. For anti-DNA antibody, a different pattern of responsiveness was observed. Individual animals of each substrain produced very similar responses in terms of the magnitude and time-course of serum anti-DNA antibody. The differences in the peak levels of the two substrains were highly significant, with lpr/lpr mice demonstrating a much greater anti-DNA antibody response than +/+ mice. In lpr/lpr mice tested for both autoantibody systems, serum anti-DNA and anti-Sm antibodies showed distinct time-courses. These studies indicate that anti-DNA and anti-Sm antibodies are expressed independently in MRL mice, with the expression of anti-DNA, but not anti-Sm antibody markedly influenced by the presence of the 1pr gene. A fundamental difference in the mechanisms involved in the generation of anti-DNA and anti-Sm antibodies is suggested by the quantitative pattern of the two responses.

Studies on rubella. II. Rubella antibodies in the cerebrospinal fluid with rubella meningoencephalitis (author's transl)

There have been a few reports of finding specific viral antibody in cerebrospinalfluid (C. S. F.) with rubella meningoencephalitis.C. S. F. from twelve patients with rubella meningoencephalitis were examinied forantibody to rubella by following techniques:Hemagglutination inhibition (HI) antibody determination was done using the standard microtitration technique. C. S. F. was not pretreated with kaolin to remove non-specific inhibitors because there was insufficient protein in C. S. F. to saturate the kaolin, and thus the range of dilution could be satarted with undiluted specimens.Neutralization test (NT) antibody was titrated employing plaque count method.Complement fixation (CF) antibody was examined with common microtitration technique.The results are as follows:1. Rubella HI antibody was found in the C.S.F. of all twelve patients. The HI antibody titer ranged from 1: 2 to 1: 128. The peak antibody level showed in acute phase and it decreased slowly depending on the day of illness. This pattern was opposite to the serum antibody pattern.2. Rubella NT antibody was found in the C.S.F. of six out of ten patients. The NT antibody titer ranged from 1: 2 to 1: 32. The NT antibody pattern depended on the day of illness and was similar to HI pattern.3. Rubella CF antibody was found in the C.S.F. of four out of ten patients. The CF antibody titer ranged from 1: 2 to 1: 8. The CF antibody pattern was similar to the NT pattern.4. An average serum/C. S. F. antibody ratio was as follows.First ten days after the onset, it was 65 for HI and 60 for NT. Ten to fifteen days after the onset, it was 153 for HI and 384 for NT and after sixteen days, 523 for HI and 768 for NT.5. No antibodies were found in the C.S.F. of the nineteen controls who had negative serum rubella HI antibody. In the case of another control group with all positive HI's in the serum, 16/19 (HI), 15/16 (NT) and 12/13 (CF) had negative titers. The positive cases were a mycoplasma encephalitis, a bacterial meningitis, an aseptic meningitis and an acute leukemia. The maximum antibody level of these cases was 1: 4.6. These results confirmed that rubella antibody could be found in the C.S.F. of the rubella meningoencephalitis and it could be diagnosed rapidly to determined the HI antibody titers in the C. S. F. It was also suggested that the rubella virus which was probably in the central nervous system could be neutralized by the antibody in the C. S. F.The further studies are required to clarify if these antibodies were produced in the central nervous systems or their localization there is due to a leak of the serum antibody through a hyperpermeable blood-brain-barrier.

Protection against group B meningococcal disease. III. Immunogenicity of serotype 2 vaccines and specificity of protection in a guinea pig model.

Protein vaccines were prepared from the serotype antigen of group B Neisseria meningitidis strain M986. The detergents Triton X-100, Emulphogene BC-720, and deoxycholate were used to removed the toxic lipopolysaccharide (LPS) portion of the serotype antigen. The LPS was most preferentially solubilized by Emulphogene. Guinea pigs were immunized with one or two doses of vaccine given intramuscularly without adjuvants and the antibody response quantitated by an enzyme-linked immunosorbant assay. Immunization with graded doses of vaccine between 25 to 200 microgram protein indicated a wide range of effective dosage and that a two-dose immunization schedule was superior to a single immunization. The vaccines elicited peak mean serum antibody levels of approximately 30 microgram/ml with bactericidal titers of 1:1,600-1:6,400. The peak antibody levels occurred 5-6 wk after immunization and persisted above preimmune levels for several months. To evaluate the protective effects of immunization, stainless steel springs were implanted subcutaneously into the guinea pigs. The resulting chambers, in unimmunized animals, could be infected with less than 100 type 2 organisms. A single 25-50 microgram dose of vaccine protected 50% of animals from challenge by 5 X 10(5) type 2 meningococci, and as little as 1 microgram vaccine significantly reduced the severity of infection. A two-dose immunization schedule was best and provided nearly complete protection for at least 4 mo against type 2 strains of meningococcal groups B, C, and Y.

Kinetics of the Antibody Response to Type III Pneumococcal Polysaccharide (SSS-III)

Abstract A simple method was described for the preparation of 125I-labeled type III pneumococcal polysaccharide (SSS-III*) with a high specific radioactivity which retained the physical and immunologic properties of native SSS-III. SSS-III* was used to study the serum and tissue levels of antigen, as well as its excretion, after i.p. injection. When an optimally immunogenic dose (0.5 µg) of antigen was given, τ;90% of the injected antigen was excreted during the first 3 days after injection; however, after day 3, the SSS-III* which remained in each mouse was firmly bound to various tissues, and &amp;lt;5 ng SSS-III* was released into the circulation daily. SSS-III* was also used in a Farr test to measure serum antibody levels; the kinetics for the appearance of PFC/spleen and serum antibody levels were measured at 24-hr intervals after immunization with 0.5 µg of antigen. Maximum PFC/spleen were observed on day 4 after immunization whereas the peak serum antibody level was seen on day 5. The decay of serum antibody level from its maximum value was much slower than that of the PFC/spleen. The data describing the distribution of SSS-III in vivo and the measurement of serum antibody levels indicated that treadmill neutralization was not a factor in determining the serum antibody levels after immunization with an optimally immunogenic dose of SSS-III.

Adjuvant Action of Capsular Polysaccharide of Klebsiella Pneumoniae on Antibody Response

Abstract The capsular polysaccharide of Klebsiella pneumoniae (CPS-K) was shown to enhance markedly antibody response of mice to various antigens. The primary antibody response to bovine serum albumin (BSA) occurred more rapidly after an injection of BSA mixed with CPS-K than after injection of the same amount of BSA in Freund's complete adjuvant (CFA), although the peak antibody level in the serum after the primary injection became higher eventually in the latter mice. In secondary and tertiary responses, much more pronounced antibody response (occasionally more than 30 mg of antibody protein per ml) was induced in mice injected first with BSA mixed with CPS-K than in those injected originally with BSA in CFA. The adjuvant action of CPS-K was also much stronger than that of lipopolysaccharide of Escherichia coli and zymosan. CPS-K could induce the antibody response of mice to syngeneic eyeball extracts which are normally non-immunogenic.

Studies on immunity to measles

Studies on immunity to measles have been in progress since 1960. Primary infection with measles virus was followed by evidence of detectable antibody by the twelfth day; peak antibody titers were observed by the twenty-first to the twenty-eighth day. Subsequently, in most instances antibody persisted for at least four years at levels capable of completely inhibiting measles infection. However, when antibody declined to minimal or undetectable levels, exposure to measles virus was usually followed by an asymptomatic infection and a booster response; under these circumstances antibody was detectable by the seventh day and peak antibody levels were observed by the twelfth day. These studies confirm the observation that one attack of measles is followed by lifelong immunity. They also provide strong support for the prediction that one inoculation of live measles-virus vaccine will confer permanent immunity.

Blood Group Antibody Levels in Hiroshima

Abstract Blood group antibody levels were measured in 526 irradiated survivors of the 1945 atomic bombing of Hiroshima and in 516 nonirradiated subjects. The study was undertaken in order to determine the age changes in antibody levels in irradiated and nonirradiated subjects, as well as to investigate the pattern of blood agglutinin levels in the Japanese population for comparison with that of Caucasians. The following observations were made: 1. In 475 people of group A, 228 of group B, and 339 of group O, the mean serum levels of anti-A and anti-B antibodies were virtually identical irrespective of the blood group of the subjects. 2. In individual group O subjects, the titers of anti-A and anti-B antibodies were very highly correlated (correlation coefficient of +.92). 3. Females exhibited higher antibody levels, although the magnitude of the difference was small. 4. Peak antibody titers were reached at age 20-30, with progressive linear regression in levels with advancing age. Peak titers in early adulthood were 5-10 times higher than those of the very elderly. 5. No correlation between blood group antibody levels and atomic irradiation was detected, whether irradiation was represented by (a) presence or absence of acute radiation symptoms in 1945, (b) distance from the hypocenter, or (c) numerical dosage estimate. 6. As one of a battery of tests of physiologic aging designed for detection of irradiation induced nonspecific aging acceleration, blood group antibody levels seem of modest value. After age 30, the linear correlation with chronologic age is -.72. 7. Differences in blood group antibody levels in Japanese and Caucasians indicate that (a) Caucasians have higher anti-A antibody levels as compared to anti-B levels than do Japanese, and (b) the peak antibody level occurs at an earlier age in Caucasians than in Japanese. It is not clear whether these differences are related to race and heredity or to external antigenic stimulation with A and B antigenic materials, but studies of blood group antibody levels in different racial groups should help elucidate the nature of these differences.