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Immunization with HIV-1 subtype B gp160-DNA induces specific as well as cross reactive immune responses in mice.

BACKGROUND & OBJECTIVES: HIV-1 gp160 is an important structural protein for the virus cell interaction and virus entry. Therefore, it is regarded as the most important target for HIV-1 vaccine development. In this study we investigated the use of HIV-1 gp160-DNA construct in eliciting specific and cross reactive cell mediated immune response in mice. METHODS: DNA segment encoding env, tat and rev genes of HIV-1 subtype B (strain BRU-2) was amplified and cloned into mammalian expression vector pCI to generate plasmid pCIBRU-TRE. Mice were injected intramuscularly four times at biweekly intervals with 100 micrograms/dose of pCIBRU-TRE in normal saline, and subsequently analysed for anti HIV-envelope (env) immune responses. RESULTS: A low antibody level was detected as determined by ELISA after 4 doses. Subsequent inoculations failed to increase the antibody titres significantly. Spleen cells from the immunized mice were used for the detection of cellular immune response by lymphocyte proliferation assays (LPA), in vitro production of cytokines and cytotoxic T lymphocyte (CTL) assays. T cell response which was seen from the second week onwards, persisted even at the end of 24 wk following the last dose. Similar levels of T cell proliferation were observed on stimulation with either homologous or heterologous peptides. Cytokine studies showed a Th1 type of response. A cross clade MHC class I restricted CTL response was observed against target cells stimulated with either homologous or heterologous HIV antigens. INTERPRETATION & CONCLUSION: This study demonstrated that DNA encoding full length HIV-1 env glycoprotein gp160 induces specific as well as cross reactive cell mediated immune responses in mice. However, the induction of antibody response was poor.

AIDS Vaccines↗

In vitro transfer of tumour-specific immunity with human 'immune' RNA.

In vitro tumour-specific immunity against lung cancer was passively transferred in the leucocyte migration inhibition system with 'immune' RNA in man; 'non-immune' RNA, on the other hand, failed to transfer such immunity, indicating the specificity of 'immune' RNA.

Antigens, Neoplasm↗

Active immunization against tetanus in guinea-pigs. An attempt to evaluate "rapid immunization" with tetanus vaccine.

The effect of 3 schedules for tetanus vaccination on the immunity developed by guinea-pigs was investigated, using 1.5 Lf adsorbed tetanus toxoid injected subcutaneously. The following injection schedules were used: a) 5 injections: initially and after 3, 7, 10, and 13 days; b) 3 injections:: initially and after 2 and 4 weeks; c) 2 injections: initially and after 4 weeks. Blood samples were taken after 1, 2, 3, 4, 6, and 8 weeks and the titres of tetanus antitoxin were recorded. No significant difference in the titres was observed within 2 weeks. Immunity was also tested by challenge with different amounts of tetanus toxin after 1 week, 10 days, 2, 3, and 8 weeks. A tendency to a higher immunity with schedule a) was observed after 10 days to 2 weeks; thereafter no acceleration of immunity could be shown. The results indicate that frequent injections over a short period of time do not establish rapid immunity against tetanus.

Animals↗

The Public Health Service action plan to improve access to immunization services. The Interagency Committee to Improve Access to Immunization Services.

The Public Health Service's Interagency Committee to Improve Access to Immunization Services (ICI) has responsibility for improving the immunization protection of the nation's children and other vulnerable populations. ICI's Action Plan to Improve Access to Immunization Services sets 14 goals with 120 action steps for improving immunization services nationwide by (a) increasing coordination among Federal health, income, housing, education, and nutrition programs; (b) reducing policy and management barriers that limit access to delivery systems, and (c) strengthening the delivery infrastructure. To accomplish the goals of the plan, there is a $72.0 million increase in funding appropriated in fiscal year 1992 specifically for this purpose. The President's Budget for fiscal year 1993 includes a $24.5 million increase for continued program implementation. The additional resources will be used to address delivery and access problems, which have been determined to be the primary factors limiting immunization for many children.

Child↗

The characterization of the exposure to immune mediated apoptosis and the regulation of immune cytotoxic activity in the environment of a neoplasm and in decidua.

Acquiring the immune-mediated apoptosis and the ability to regulate the cytotoxic immune response are the main phenomena playing fundamental roles in such situations as neoplasm survival and creation of immune tolerance during pregnancy. The aim of this study was to investigate these phenomena through the evaluation of metallothionein and RCAS1 proteins in neoplasm and its healthy environment (clear surgical margin), physiological conditions in placenta and its environment (decidua) and the comparison to non-neoplasmatic lesions originating from the environment (nasal polyps, endometriosis). We have shown that the growth of RCAS1 expression was simultaneous to the infiltration of activated immunological cells of tumor environment as well as decidua. The activity of immunological cells was in our study selectively suppressed. Metallothionein expression growth was also observed in healthy tumors stroma and in decidua probably in response to the growing cytotoxic activity and tumor spread. Alterations in RCAS1 and Metallothionein expression seem to be associated with local immune dysfunction in nasal polyps and endometriosis. In conclusion, the ability to compensate the growing cytotoxic immune response is physiologically observed in decidua, the lost of this ability in tumor environment might participate in the development of tumor spread.

Antigens, Neoplasm↗

Early induction of immune resistance against leukemia in lethally total body irradiated mice reconstituted with syngeneic bone marrow cells obtained from previously immunized donor mice.

BALB/c x DBA/2 F1 (CD2F1) mice were lethally irradiated and reconstituted with syngeneic bone marrow cells (SBMC) obtained from normal or previously immunized (against L1210 lymphatic leukemia) donors. These recipient mice are called TBI + SBMT or TBI + Imm-SBMT mice, respectively. TBI + Imm-SBMT, but not TBI + SBMT mice, were able to develop strong immune resistance against L1210 leukemia, but not against MOPC 104E plasmacytoma, if the immunization procedure (four i.p. injections at weekly intervals of immunogenic L1210 cells) was started as early as 7 days posttransplantation. Incubation of Imm-SBMC with mafosfamide (ASTA Z7654) before grafting abrogated the ability of the recipient mice to develop early resistance against the leukemia. Treatment of Imm-SBMC with monoclonal or polyclonal antibodies plus complement showed that two or three subpopulations of Imm-SBMC were necessary for the transfer of immune information against leukemia: T lymphocytes with phenotype Thy 1.2+, Lyt 1+2-, I-Ad-, macrophages with phenotype Mac-1+, I-Ad-, and probably asialo-GM 1+ cells. Recipient mice immunized against L1210 leukemia before TBI + SBMT do not develop early resistance to the leukemia.

Animals↗

Suppressor T cells regulating the cell-mediated immune response to Pseudomonas aeruginosa can be generated by immunization with anti-bacterial T cells.

We previously demonstrated that immunization with low (10 micrograms) doses of high m.w. polysaccharide from the gram-negative bacterium Pseudomonas aeruginosa generates T cells that suppress the ability of antibacterial T cells (Tab) to protect against bacterial infection. The current studies indicate that Ts cells with properties identical to those elicited by low dose polysaccharide immunization can be generated by immunization with Tab. Tab-elicited Ts cells can abrogate in vivo induction and in vitro and in vivo expression of antibacterial T cell activity. Tab-elicited Ts are Ag-specific and H-2 restricted in their suppressor activity. Non-immune T cells fail to elicit suppressor activity. These studies provide additional evidence that the protective T cell response to P. aeruginosa is controlled by a network of T cells that are probably recognizing idiotypic determinants on P. aeruginosa-immune T and B cells.

Animals↗

[Passive immunization with an anti-oCRF41 immune serum inhibits the circadian increase of plasma ACTH in rats].

For 24 hrs. after i.v. injection of 1 ml of an undiluted immune serum raised against oCRF41, the diurnal surge of plasma ACTH dropped to a short-lived limited rise above baseline level. On the second day after injection, the ACTH level in treated rats rose to a subnormal level, although both plasma dilution of the immune serum and its binding capacity in the plasma remained unchanged throughout the experiment. Plasma corticosterone, on the contrary, displayed a normal circadian rhythm during the entire experiment. However, in animals given a second injection of 0.5 ml oCRF41 immune serum 32 hrs. after the first, both ACTH and corticosterone titers fell rapidly below their circadian minimal levels in controls. Concomitantly, the concentration of immune serum in the peripheral plasma, and its capacity to bind to oCRF, rose by 50%. The major role of CRF41 as a diurnal trigger of the circadian rhythm of ACTH is discussed, as well as the limits of passive immunization.

Adrenocorticotropic Hormone↗

[Anti-Brucella immunity transferred by immune serum and that transferred by splenic lymphocytes cannot be added].

Immune serum and spleen cells from mice vaccinated with a cell-wall fraction (PG) from Brucella were previously shown to transfer a good protection to mice against a virulent Brucella challenge. This protection estimated by spleen and liver time-course infection was similar to that afforded by vaccination. In present experiments, DBA/2 mice were first transferred with either immune serum from infected mice, splenic cells from mice intravenously vaccinated with PG fraction 28 days previously, or both immune serum and splenic cells. In this case, the serum was either injected before the challenge, as were the splenic cells, or 2 days after it in order to reduce the lowering effect of the serum on level of initial colonization of the spleen. The transferred mice were then intravenously challenged with the virulent strain B. abortus 544 and liver and spleen counts were performed on groups of five mice weekly up to six weeks. Immune serum and splenic cells from vaccinated mice were again shown to strongly reduce the time-course of splenic infection. However addition of both effects was observed for a short time only two and three weeks post-challenge and only when the serum was injected after the challenge. In contrast, no additive or even an antagonistic effect was observed after the 21st day. Liver infection was not notably modified by both immune serum or splenic cells (except increment of initial colonisation by serum) until the 21st day when both helped reduce the course of infection. However again no additive effect was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The role of IgG1 hypergammaglobulinaemia in immunity to the gastrointestinal nematode Nematospiroides dubius. The immunochemical purification, antigen-specificity and in vivo anti-parasite effect of IgG1 from immune serum.

Nematospiroides dubius, in common with many other species of metazoan parasite, induces an IgG1 hypergammaglobulinaemia during the course of infection. In the present study, immune sera raised in CFLP mice by repeated infection contained 24 ng/ml IgG1 compared with a resting level of 2.4 mg/ml. IgG2a and IgG2b levels were depressed following infection from 1.5 to 0.6 mg/ml and 0.64 to 0.42 mg/ml respectively. IgM levels were unaltered by infection (0.16 mg/ml) whilst IgA levels increased from 0.7 to 1.2 mg/ml. Immunochemical fractionation of immune sera by a combination of affinity chromatography and gel filtration revealed that the anti-parasite activity of the original serum could be largely accounted for by purified IgG1 fractions as assessed by immunoprecipitin and immunofluorescence assays. Purified IgG1 was shown to react with antigenic components common to both adult homogenate and adult excretory-secretory antigen. In addition, absorption studies revealed that as much as 48% of purified IgG1 from immune serum reacted with adult N. dubius antigen. In vivo, IgG1 was the only purified immunoglobulin isotype to cause significant reduction in worm numbers in the gastrointestinal tract when administered alone, and to have any noticeable co-operative effect when administered in conjunction with immune mesenteric lymph node cells. IgG1 also caused severe stunting of worms, and promoted the adherence of peritoneal exudate cells to the worm surface in vitro. It is suggested that one mechanism by which immune mesenteric lymph-node cells exert their protective activity following cell transfer is by elevating IgG1 levels in recipient mice.

Animals↗

[Effect of colostral antibodies on the development of immunity in piglets immunized with live vaccine].

Pigs of sows treated with a live vaccine were in turn vaccinated with a live vaccine at different age. Part of them were challenged with a virus at 60 days of age, the remaining -- at 90 days. The pigs were kept under clinical observation, and were killed on the 10th day following challenge in order to be thoroughly investigated. It was found that the passive immunity (virus-neutralizing antibodies) in pigs of twice (live vaccine) treated sows persisted for 4 to 5 weeks after birth. It dropped steplike, however, the interference of the vaccinal virus speeded up the process -- the earlier the vaccination the faster the exhaustion of immunity. The passive immunity was found to neutralize the vaccinal virus and hamper the building of active immunity. The presence of eosinophile leukocytes in the lymph nodes, tonsils, and spleen of the vaccinated pigs spoke of an immune reaction.

Animals↗

Studies on the immune protection to murine experimental brucellosis conferred by Brucella fractions. I. Positive role of immune serum.

Mouse inoculation with three different phenol-insoluble fractions extracted from Brucella melitensis (fractions 'PI', '4A' and '5') induces an acceleration of the blood clearance of i.v. inoculated live Brucella and a diminution of the rate of multiplication of the injected bacteria in the spleen. Preincubation of the challenge inoculum in immune serum or i.p. injections of immune serum confer a good specific protection to non-immunized hosts. The results observed with fractionated sera suggest that, not only antibodies, but also other serum constituents may participate in the protective activity of immune sera. This discussed in terms of the respective importance of humoral and cellular immunity to Brucella and of the choice of the best preparations for human or animal vaccination.

Animals↗

Delays in immunizations of high-risk infants during the first two years of life: special care for the high-risk infant should not mean special immunization schedules.

Because experience in our newborn intensive care unit follow-up clinic since 1982 suggested that immunizations of newborn intensive care unit graduates in the first 2 years of life were inappropriately delayed, questionnaires were sent to families and to the four categories of primary care providers (family practitioners, pediatricians, local health clinics, and neonatalogists) in our region to assess immunization rates and practices. Delays in the first diphtheria, tetanus, and pertussis immunization and the polio vaccine were greater the less the birth weight and less the gestational age of the infant. Delays in subsequent immunizations were considerable and did not correlate with gestational age. A substantial proportion of primary care providers are not immunizing infants in compliance with the American Academy of Pediatrics recommendation, but some improvement is seen when the time period 1982 to 1986 is compared with 1987 to 1991.

Female↗

HIV gp120-specific cell-mediated immune responses in mice after oral immunization with recombinant Salmonella.

Salmonella is of great interest as a potential human immunodeficiency virus vaccine vector because of its ability to elicit potent mucosal and systemic immune responses when administered orally. To determine whether such a vaccine could elicit an immune response in mice, plasmids expressing HIV gp120-LAI were introduced into attenuated S. typhimurium. Three serial doses of 10(10) recombinant organisms were administered orally to BALB/c mice at 2-week intervals. Immunized mice but not control mice demonstrated proliferative T cell responses to gp120-LAI, comparable in magnitude to the proliferative responses to Salmonella antigens. Immunized mice had detectable serum and intestinal Salmonella-specific IgA and serum Salmonella-specific IgG. However, no gp120-specific antibody was detected in either serum or intestinal washes. These results indicate that live recombinant Salmonella-based vaccine constructs can induce HIV-specific cellular immune responses in vivo.

AIDS Vaccines↗

Antibodies given orally in the neonatal period can affect the immune response for two generations: evidence for active maternal influence on the newborn's immune system.

Two day old Wistar rats were tube fed with 1 or 10 micrograms of a mouse IgG1 monoclonal anti-idiotypic (a-Id) antibody that was directed against an anti-Escherichia coli-K13 capsular polysaccharide antibody. A control group was given 10 micrograms of an unrelated control antibody. Six weeks after the administration of antibodies, the rats were intestinally colonised with an ovalbumin (OVA)-producing E. coli O6K13 strain. At 8 weeks of age, the male rats (first generation) and the offsprings of the female rats (second generation), were parenterally immunised with OVA and dead wild type E. coli O6K13, and the immune response was followed. In the rats of the first generation, there were no major differences between the groups in the immune response to the bacterium. However, the offspring of the neonatally a-Id administered rats had a profoundly affected immune response to the idiotypically connected antigen K13, but also to other antigens on the bacteria. Thus, a-Id treatment in the first generation gave, in the second generation, a greatly enhanced serum antibody response to the spatially related antigens OVA and O6 LPS, as well as to the idiotypically connected antigen K13. Concurrently, the in vitro spleen cell proliferative response to both OVA and the wild type bacterium was lowered. Overall, greater effects were seen with the higher dose of a-Id. In conclusion, our results demonstrate that by giving monoclonal antibodies idiotypically connected to a single bacterial component to neonatal rats, one profoundly influence the immune response also to other-spatially related-bacterial antigens in their offsprings.

Administration, Oral↗

Suppression of the immune response to Listeria monocytogenes. I. Immune complexes inhibit resistance.

Murine infection with the facultative intracellular pathogen Listeria monocytogenes was studied as a model of cell-mediated immunity. Overwhelming lethal infection with Listeria developed when mice were given a secondary challenge with a protein antigen at the same time as Listeria infection. Three days after infection, mice immunized with ovalbumin and then challenged with Listeria and ovalbumin had up to 2.1(10)6 times as many viable Listeria organisms in their spleens as mice challenged only with Listeria. The suppressive effect of secondary challenge with a protein antigen was found to be antigen-specific, transient, and not dependent on route of challenge with either Listeria or ovalbumin. Secondary challenge with a protein antigen suppressed both the primary and the secondary responses to Listeria. Immune serum, or affinity-purified antibody, was found to transfer the suppressive effect to nonimmune mice. These findings demonstrate that acute formation of immune complexes causes a transient state of high susceptibility to infection with an intracellular pathogen. Possible mechanisms for, and implications of, these findings are discussed.

Animals↗

Immunization status of hospitalized preschool-age children. The need for hospital-based immunization programs.

The records of 102 hospitalized preschool-age children were reviewed to determine their immunization status. Nineteen children (19%) had a documented delay in immunizations. None of these children were immunized prior to hospital discharge, although no contraindications to immunization had been identified. Two to five months after hospital discharge, ten patients (53%) were still deficient. Compliance with recommended immunization schedules is not adequately addressed during hospital admissions.

Child, Preschool↗

Parenteral fat emulsions and immune adherence. The effects of triglycerides on red cell and neutrophil immune adherence in vitro and in vivo.

Parenteral fat emulsions may not only exert nutritional effects but may also affect immune adherence phenomena and red cell morphology. Red cell immune adherence (RCIA) was augmented in vitro by 0.05% to 0.1% Intralipid. Similar augmentation of RCIA was observed by peanut oil, corn oil, half-and-half cream, paraffin oil, and human low-density lipoprotein fractions. Neutrophil immune adherence was augmented in vitro by 0.2% to 1.5% of Intralipid. The effects of fat emulsions in vivo were studied in ten patients who received intralipid for nutritional purposes. Red cell immune adherence was augmented in five of ten patients and inhibited in four of ten patients. Neutrophil immune adherence was augmented in two of ten patients. Cytotoxic red cell transformations were evident in five of ten patients. Depression of RCIA in four of five patients was associated with cytotoxic red cell transformations.

Adult↗