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PubMed1984

Delayed secondary immune response in mice immunized with Toxoplasma antigens and its effect for protection against Toxoplasma gondii.

Primary immune response by mice immunized with Toxoplasma peritoneal exudate (PE) was produced slowly at a low level. To induce high Toxoplasma antibodies, mice should be boostered after the primary immune response reached the peak in 4 weeks or later. Immunization of mice with PE alone in 4 weeks could suppress the growth of Toxoplasma but could not accomplish protection. Two of 9 mice immunized with PE in complete Freund's adjuvant (CFA), and 16 of 27 mice immunized with PE containing Toxoplasma ( ToxoPE ) in CFA were protected against a challenge of 1 X 10(3) Toxoplasma, RH strain. The mice surviving to the challenge showed complete protection against a rechallenge of higher dose, 1 X 10(6) RH strain. Their ascites were very high in LA titer and would be a great source for obtaining high titer antibodies to Toxoplasma without contamination of host serum components. Biological characters of Toxoplasma, RH strain, in chronic infection of mice are discussed.

Animals↗
PubMed1981

Mechanism of action of BCG-tumor cell vaccines in the generation of systemic tumor immunity. II. Influence of the local inflammatory response on immune reactivity.

The intradermal injection of a vaccine composed of 10(7) X-irradiated syngeneic hepatocarcinoma line 10 (L10) cells admixed with 10(8) Mycobacterium bovis strain BCG into inbred Sewall Wright strain 2 guinea pigs induces a local inflammatory reaction and effectively immunizes against a contralateral challenge with viable L10 cells. The relationship between the local inflammatory reaction and the generation of tumor immunity was studied. Immunization against L10 was most effective when both L10 cells and BCG were injected into the same site, less effective when they were injected into separate sites with common lymphatic drainage, and not effective when they were injected at totally separate sites. Enzymatic dissociation of dermal vaccination sites revealed that vaccination with BCG and L10 cells combined induced a significantly greater inflammatory response than did vaccination with BCG alone or L10 cells alone; the inflammatory response was also greater than the combination of these individual responses, suggesting that BCG and L10 cells interacted synergistically in the elicitation of an inflammatory response. Sites receiving a combined vaccine of BCG and L10 cells were infiltrated rapidly by inflammatory cells, and surgical excision of these sites as early as 24 hours after vaccine administration did not affect significantly the development of immune responsiveness. However, vaccination sites induced by the injection of BCG and L10 cells at separate but adjacent sites were slowly infiltrated by inflammatory cells, and surgical removal of these sites within 96 hours of vaccination inhibited later immune responsiveness. Quantitative cellular analysis of these inflammatory reactions showed that inflammation was related to tumor-reactive immunity such that the greater the initial inflammatory process, the greater the resistance to tumor challenge.

Adjuvants, Immunologic↗
PubMed1980

Immune elimination and immune retention: the relationship between antigen retained in the foot and the elicitation of footpad swelling.

We determined whether (1) long term antigen retention is present in distal sites after footpad challenge of immune mice; (2) if antigen retained in the foot is selectively localized; and (3) if the foot is adversely affected by the retained antigen. Mice immune or non-immune to human serum albumin (HSA) were injected in the hind footpads with 125I-HSA. In immune mice rapid clearance of radiolabel occurred in the liver, lungs, kidney, blood and urine but radiolabel was retained in the hind feet, draining lymph nodes and spleen. Non-immune mice rapidly cleared radiolabel from these sites. Autoradiography revealed that most of the radiolabel in the feet was in flexor tendons and tendon sheaths. Electron microscope autoradiography indicated that antigen was associated with collagen at the tendon surface, but not with cells or cell processes. Radiolabel solubilized from the feet, lymph nodes and spleen could be specifically precipitated with rabbit anti-HSA. Histological examination of the tendon and surrounding tissues did not show that retained antigen was causing inflammation or chronic tissue damage. Nanogram levels of antigen could elicit swelling in the sensitized foot even if the antigen was injected at a remote site, but mice immunized by other routes or against other antigens did not show footpad swelling. Antigen retained on collagenous tissues may induce hypersensitivity and thus play a role in rheumatic diseases.

Animals↗
PubMed1995

Protective CTL-dependent immunity and enhanced immunopathology in mice immunized by particle bombardment with DNA encoding an internal virion protein.

Anti-viral CTL were induced in vitro using a particle bombardment device or "gene-gun" to deliver plasmid DNA encoding the nucleoprotein of the lymphocytic choriomeningitis virus (LCMV). Using this plasmid we were able to study T cell-mediated immunity in the absence of a neutralizing Ab response. Upon a single DNA immunization, a nearly 2 log10 reduction in splenic viral titers was observed 3 days after LCMV infection. After two or three immunizations a greater than 3 log10 inhibition of viral titers in the spleen was observed, with most animals having no detectable virus. C57BL/6 mice immunized with DNA encoding the nucleoprotein gene were also challenged with LCMV intracranially. Upon intracranial challenge, vaccinated animals displayed either protection or enhanced immunopathology leading to accelerated kinetics of death. Using limiting dilution analysis it was possible to detect LCMV-specific CTL precursors in both the spleen and lymph nodes of vaccinated animals. C57BL/6 mice inoculated with DNA demonstrated an anamnestic CTL response detectable at day 4 after LCMV challenge. Thus DNA vaccines are capable of inducing an anti-viral T cell response that can inhibit viral replication and mediate either protective immunity or immunopathology. Vaccination with DNA may therefore provide a useful alternative to current viral or subunit vaccines once the efficacy of immunization with DNA is optimized.

Amino Acid Sequence↗
PubMed1994

Murine immune response to cells transfected with human MUC1: immunization with cellular and synthetic antigens.

Humans with breast cancer have T-cells in their lymph nodes which recognize a peptide sequence within the variable number of tandem repeats of the mammary mucin, MUC1, which is overexpressed in breast cancer. To find means of making this recognition event into a potent immune response to breast cancer, we used a murine tumor model and have examined the parameters of the immune response to human mucin (MUC1) expressed in murine BALB/c 3T3 cells. We then sought to boost this response with MUC1-containing synthetic peptides, fusion proteins, and natural mucin (HMFG). MUC1+3T3 cells were found to be rejected by BALB/c mice by day 15 due to a cellular [CD3+, Ly2+ (CD8+)] response. The cellular rejection response was accompanied by the generation of CD8+ cytotoxic T-cells, CD4+ delayed-type hypersensitivity, and little anti-MUC1 antibody. This immune response is presumably of the TH1 type (which occurs in CD8 as well as CD4 cells) of CD8+ cytotoxic cells. By contrast, mice immunized with the MUC1 synthetic peptide, a fusion protein, or HMFG have good antibody responses, a delayed-type hypersensitivity reaction, but no cytotoxic T-cells and less tumor protection, possibly a TH2 type response. We conclude that CD8+ cytotoxic anti-mucin cells can produce significant antitumor responses in vivo to a human "tumor" antigen expressed in murine cells; immunization with soluble synthetic or native materials leads to the "humoral" (TH2) type of immunity, and efforts need to be made to convert this to a TH1-type response.

3T3 Cells↗
PubMed1993

Statement on pertussis immunization. National Advisory Committee on Immunization.

The following recommendations on pertussis vaccine from the National Advisory Committee on Immunization will appear in the fourth edition of the Canadian Immunization Guide, scheduled for publication in autumn 1993. These revised recommendations represent a major change in vaccine usage and take account of the current understanding of adverse events associated with use of pertussis vaccine. Most adverse events are no longer contraindications to further immunization; only anaphylactic reaction to a previous dose remains an absolute contraindication to pertussis immunization. Other adverse reactions for which there are no sequelae or that have not been proven to be caused by the vaccine are no longer considered valid reasons for withholding immunization. It is hoped that simplification of the contraindications will improve vaccine utilization and achieve higher levels of age-appropriate immunization.

Canada↗
PubMed1993

[The epidemic process in infections before and after active immunization. II. Changes in the number of susceptible individuals in the population during a natural epidemic and its control by active immunization].

Based on the long-term follow-up of the incidence of some infectious diseases in the district and calculations of the actual number of infected subjects, the authors present an estimate of the ratio of susceptible and immune subjects during the unimpaired epidemic process. The epidemic process develops from the lowest range of immune subjects and stops at the highest range. The highest range thus gives the ratio of immune subjects which must be achieved or maintained by active immunization to achieve elimination of a given infection. The authors demonstrate on the model infection the mechanism by which after immunization the shift of infections to higher age groups occurs, and during introduction of the infection not only contact infections occur, but epidemic incidence develops. The restoration of some infections after years of elimination is to a restricted extent a natural phenomenon and does not imply failure of active immunization.

Chickenpox↗
PubMed1996

Protective antitumor immunity induced by immunization with completely allogeneic tumor cells.

We have shown previously that immunization of B6 mice (H-2b) with tumor cells of B6 origin transformed by the human adenovirus type 5 early region 1 (Ad5E1) induces an H-2Db-restricted CTL response against an E1B-encoded CTL epitope. We now report that immunization of B6 mice with Ad5E1-transformed tumor cells of BALB/c origin (H-2d), apart from inducing a B6 anti-BALB/c allo-response, also induces a strong CTL response against the E1B-encoded H-2Db-presented CTL epitope. BALB/c Ad5E1-transformed tumor cells are not recognized by E1B-specific CTLs, indicating that nontumor cells have processed the E1B-encoded CTL antigen and have presented the E1B peptide to E1B-specific CTLs. These data also show that the B6 anti-BALB/c allo-response does not overwhelm the anti-E1B response induced by the allogeneic tumor cell vaccination. Moreover, B6 mice immunized with allogeneic BALB/c Ad5E1 cells are, in contrast to mice vaccinated with untransformed BALB/c cells, protected against a subsequent challenge with B6 Ad5E1-expressing tumor cells. These data show that immunization with completely allogeneic tumor cells can lead to protective syngeneic antitumor immunity, indicating that completely allogeneic tumor cell vaccines can be used for the induction of antitumor immunity.

Animals↗
PubMed1996

IL-12 enhances vaccine-induced immunity to schistosomes by augmenting both humoral and cell-mediated immune responses against the parasite.

The production of Th1-type cytokines is associated with strong cell-mediated immunity, while Th2-type cytokines typically dominate humoral immune responses. In mice vaccinated a single time with attenuated cercariae of Schistosoma mansoni, the protection induced is associated with Th1 cytokine-dependent, cell-mediated immunity. In contrast, mice vaccinated multiple times display a more Th2-type dominant cytokine response and develop Ab-dependent resistance. We have previously shown that IL-12 enhances cell-mediated immunity in singly vaccinated mice. In the present study, we asked what effects administering IL-12 as an adjuvant would have on the development of a protective humoral response in multiply immunized animals. We found that multiply immunized/IL-12-treated mice displayed a marked increase in resistance to challenge infection, with some animals demonstrating complete protection. The IL-12-vaccinated mice developed strongly polarized Th1 responses but, importantly, also showed significant increases in parasite-specific Ab and, in particular, IgG2a, IgG2b, and IgG1 isotypes. Passive transfer demonstrated an enhanced ability of serum from these animals to protect naive recipients. In addition, animals vaccinated in the presence of IL-12 also developed macrophages with increased nitric oxide-dependent killing activity against the parasites. Together, these data demonstrate that IL-12, initially described as an adjuvant for cell-mediated immunity, may be used to simultaneously to promote both humoral and cell-mediated protective responses against infection.

Animals↗
PubMed1997

The involvement of immune reactions in cardiac damage during acute myocardial infarction: role of cell-mediated immune response.

This study was undertaken with the aim of investigating humoral and cell-mediated immune response in acute myocardial infarction (AMI) as possible mechanisms involved in the infarction enlargement. Twenty three patients with first AMI and 15 healthy volunteers were examined. Of the AMI patients, 14 had extensive infarction (group A), while 9 patients had small infarction (group B). Immunologic analyses were performed at admission, and repeated after 3, 7, 14 and 21 days of the acute event. Following parameters were tested: number of CD3+, CD4+, CD8+ and CD20+ cells; serum IgG, IgA, IgM, C3, C4, immune complex and anticardiac antibody levels; polymorphonuclear cell (PMN) function (chemotaxis, phagocytosis, metabolic activity); leukocyte migration in vitro in the presence of water-soluble homologous heart extract. It was demonstrated that the number of B cells, serum IgG, C3, immune complex and anticardiac antibody levels were elevated from 7th-14th days after AMI. Concerning these parameters, however, no significant differences were obtained between group A and group B of AMI patients. Chemotaxis and metabolic activity of peripheral blood PMN, but not phagocytosis, were enhanced during AMI, again changes of PMN did not correlate with the extension of infarction. In contrast, leukocyte migration inhibition in vitro revealed that only patients with extensive AMI have developed positive reaction during the first 14 days after the onset of the disease, while leukocyte inhibition reaction appeared in patients with nonextensive AMI not earlier than the 21st day after the infarction. These findings demonstrate generation of immune reactivity during AMI and indicate that humoral immune response seems more likely to be an epiphenomenon related to tissue necrosis, while cell-mediated immune reactions could influence the extensiveness of cardiac damage.

Acute Disease↗
PubMed1998

Enhancement of cell-mediated immunity in melanoma patients immunized with murine anti-idiotypic monoclonal antibodies (MELIMMUNE) that mimic the high molecular weight proteoglycan antigen.

The purpose of this study was to determine whether a combination of two anti-idiotypic antibodies that mimic the high molecular weight proteoglycan antigen found on most melanoma tumors was capable of enhancing cellular immunity in vaccinated high-risk patients with melanoma. Twenty-eight stage I-IV high-risk patients with melanoma were immunized with a mixture of variable concentrations of MELIMMUNE-1 and MELIMMUNE-2, along with the adjuvant SAF-m, using two immunization schedules. Peripheral blood mononuclear cells were collected before the first immunization and 4 weeks after the final immunization and tested for in vitro proliferation to MELIMMUNE-1 and MELIMMUNE-2 and for cytotoxicity against 51Cr-labeled target cell lines. Additionally, supernatants from in vitro proliferation cultures were tested for interleukin 10 and IFN-gamma levels. Significant in vitro proliferation to MELIMMUNE-1 and MELIMMUNE-2 were observed in postimmunization samples but not in prevaccination samples. The mean stimulation index for MELIMMUNE-2 (33.7 +/- 0.6) was significantly higher than that for MELIMMUNE-1 (13.9 +/- 0.3; P < 0.025). Supernatants obtained from 78% of the in vitro stimulated cultures pre- or postvaccination contained significant levels of interleukin 10 (range, 0.43-142 pg/ml), whereas IFN-gamma levels were elevated in 53% of postvaccination samples (range, 3-245 pg/ml) but not prevaccination samples. More importantly, we were able to generate specific CTL responses in 43% of the patients, which correlated with elevated IFN-gamma levels. These results indicate that MELIMMUNE enhances cell-mediated immunity in patients with melanoma.

Antibodies, Anti-Idiotypic↗
PubMedDate not supplied

Simultaneous passive and active immunization against hepatitis B: noninterference of hepatitis B immune globulin with the anti-HBs response to reduced doses of heat-inactivated hepatitis B vaccine.

The effect of simultaneous administration of hepatitis B immune globulin on the antibody response to a low dose of heat-inactivated hepatitis B vaccine was investigated in 175 health care workers. Subjects were divided into four groups: Groups I and II received 3 monthly injections of a reduced dose (0.6 microgram) of a heat-inactivated hepatitis B vaccine (the usual dose being 3 micrograms) along with 500 IU of hepatitis B immune globulin simultaneously with the first injection of vaccine; Groups III and IV received the vaccine only. In addition, Groups I and III received a final booster injection with 0.6 microgram of the vaccine 8 months after the initial injection. Anti-HBs passively acquired from hepatitis B immune globulin did not interfere with the development of an active antibody response to the vaccine: the anti-HBs conversion rates were similar in persons treated with the combined regimen (89%) as in those who received the vaccine only (91%). At 3 and 5 months after the first injection, however, anti-HBs titers in the recipients of vaccine alone were slightly but statistically significantly higher than those of persons who received both hepatitis B immune globulin and vaccine; but at 8 months, this difference was no longer statistically significant. After a booster inoculation at 8 months, the geometric mean titer of anti-HBs increased 7- to 8-fold in antibody-positive vaccinees, regardless of whether hepatitis B immune globulin had been given earlier. Moreover, 6 of 13 nonresponders to the initial three vaccine injections developed anti-HBs after the booster inoculation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed2005

Induction of tumor immunity and cytotoxic t lymphocyte responses using dendritic cells transduced by adenoviral vectors encoding HBsAg: comparison to protein immunization.

Dendritic cells (DC) are specialized antigen-presenting cells with powerful immunostimulatory properties. Their use for induction of anti-tumor immunity has been limited by several factors, including identification of appropriate tumor-associated antigens, delivery of antigens to DC, and maintaining DC in a highly activated state. Here, DC propagated in vitro were transduced with an adenoviral (Ad) vector to express hepatitis B surface antigen (HBsAg), an antigen present in hepatocellular carcinoma (HCC). Many patients with HCC demonstrate evidence of prior HBV exposure, suggesting that the presence of the virus in a quiescent state may promote tumorigenesis. Ad-HBsAg-transduced DC stimulated strong cytotoxic T lymphocyte (CTL) responses to HBsAg-expressing tumor cells, and protected mice from lethal tumor challenge. Immunity was antigen-specific, as wild-type tumor (HBsAg -) grew normally. Furthermore, DC transduced with an irrelevant vector had no effect. Vaccination with HBsAg protein, a clinically utilized preparation that confers immunity to HBV infection, did not protect against tumor challenge even though it induced a strong antibody response. These studies describe for the first time the contributions of humoral and cellular immune responses to tumor immunity induced by Ad-transduced DC compared to protein vaccination.

Adenoviridae↗
PubMed1982

Development of chronic pulmonary inflammation in immunized guinea pigs by aerosol challenge with antigen: relationship of immune complex disease and cell-mediated hypersensitivity.

Immunized guinea pigs develop immune complex disease (ICD) in the lungs after a single aerosol challenge with specific antigen. In the current study, immunized guinea pigs developed chronic pulmonary inflammation and cellular immunity (CI) in the lungs when aerosol challenged daily with specific antigen for 2 wk. When immune serum was passively transferred to normal recipients that were then aerosol challenged with specific antigen for 2 wk, chronic pulmonary inflammation and CI did not develop. These results suggest that ICD produced by passive transfer of serum and subsequent aerosol exposure to antigen was inadequate to cause chronic pulmonary inflammation and CI. The development of chronic pulmonary inflammation by aerosol challenge with antigen was suppresed with cobra venom factor. However, because of other studies, we attribute this suppression to the diminution of complement (C) factors in the alternative C pathway that affect macrophage mobility rather than to the depletion of C5a, which is important in the development of ICD.

Aerosols↗
PubMed2001

Long-term persistence and recall of immune responses in aged mice after mucosal immunization.

To evaluate the retention of memory in the mucosal immune system of aged animals, 2-year-old mice that had been immunized intragastrically at 3 months of age with Streptococcus mutans protein AgI/II coupled to the B subunit of cholera toxin (CTB) were evaluated by ELISA for antibodies to AgI/II and CT in serum, saliva, and vaginal wash. To evaluate recall responses, mice were then immunized intragastrically with AgI/II-CTB, in comparison with previously unimmunized controls. Those that had been primed in their youth showed a more rapid antibody response in serum (immunoglobulin G (IgG)) and secretions (IgA), but all animals eventually responded to a similar degree after the third dose. Mice immunized at 3 months also retained for 2 years spleen cells capable of proliferating in vitro in response to AgI/II. These data show that aged mice retain the ability to mount immune responses to mucosally presented immunogens and that memory to mucosally presented immunogens can persist for almost the whole lifetime of a mouse.

Adjuvants, Immunologic↗
PubMed2004

Systemic and mucosal immunity in rhesus macaques immunized with HIV-1 peptide and gp120 conjugated to Brucella abortus.

HIV vaccine testing in primates is an important method for determining the possibility of vaccine benefit in humans. Goals of HIV-1 vaccination include establishing neutralizing antibodies and a strong CD8(+) T-cell response. We tested a novel vaccine conjugate for its ability to elicit relevant immune responses to HIV proteins and peptides in rhesus macaques. A neutralizing epitope, V3 loop peptide from HIV-1 envelope, was coupled to heat-inactivated Brucella abortus (V3-HKBA). Rhesus macaques were immunized with this conjugate in the anterior thigh. After two immunizations V3-specific antibodies were found in the sera and at mucosal sites. Neutralizing activity of these antibodies was demonstrated by syncytia inhibition assays. Cellular immune recall responses were demonstrated by antigen-specific induction of interferon-gamma and Regulation on Activation Noraml T Cell Expressed and Secreted (RANTES) secretion in vitro. These results confirm and extend preliminary studies in mice that suggest HKBA is an effective carrier that promotes neutralizing antibody secretion at relevant mucosal sites, as well as cellular immune responses that are correlated with viral protection.

AIDS Vaccines↗
PubMed1998

Duration of protective immunity conferred by maternal tetanus toxoid immunization: further evidence from Matlab, Bangladesh.

OBJECTIVES: Although maternal tetanus immunization has been shown to be highly effective in the prevention of neonatal tetanus, unresolved questions remain concerning the required minimum number of doses and the resulting duration of effective immunity. This study examined the duration of effective immunity against neonatal tetanus provided by maternal tetanus immunization. METHODS: A randomized, double-blind cholera vaccine trial of 41,571 children and nonpregnant adult women carried out in 1974 in the Matlab comparison area of rural Bangladesh provided a unique opportunity to address dose and immunity issues. RESULTS: Children of women who received either 1 or 2 injections of tetanus toxoid experienced 4- to 14-day mortality levels consistently lower than those of children of unimmunized mothers. Analysis of neonatal-tetanus-related mortality showed that 2 injections of tetanus toxoid provided significant protection for subsequent durations of up to 12 or 13 years. CONCLUSIONS: The data demonstrate that a limited-dose regimen of maternal tetanus toxoid provides significant and extended protection against the risk of neonatal tetanus death.

Adolescent↗
PubMed1982

Sensitization of offspring of Leishmania donovani-infected hamsters to immunization and of offspring of immunized hamsters to challenge.

Female hamsters, infected intracardially (i.c.) with 1.0--2.0 x 10(5) amastigotes of Leishmania donovani produced offspring, following mating, which, when immunized subcutaneously with 1.0 x 10(7) amastigotes at 8 weeks of age, were more resistant to i.c. challenge 6 weeks later than were hamsters born to non-infected mothers. Offspring of mothers infected with as many as 6.0 x 10(6) amastigotes demonstrated no greater capacity for immunization than did those of mothers infected with 1.0 x 10(5) amastigotes. Sensitization of offspring of infected mothers apparently is transplacental since the effect could only be seen in offspring of infected mothers and not in those of normal mothers weaned by infected dams. Offspring of female hamsters immunized by footpad inoculation of 1.0 x 10(7) amastigotes exhibited reduced spleen parasite burdens when challenged at 8.5 weeks of age and reduced spleen and liver parasite burdens when challenged at 16 weeks of age, compared to offspring of nonimmunized hamsters; this effect was not noted following challenge of offspring of the two groups within 1 day of weaning. The passage of parasites from mother to young during gestation and/or nursing apparently does not occur since, at 125 days of age, no parasites were observed in spleen or liver impression smears of offspring of hamsters infected i.c. with 6.0 x 10(6) amastigotes while parasites were seen in such smears of hamsters infected, 120 days previously, with 10 amastigotes i.c. Thus, sensitization to immunization in offspring of infected hamsters and to challenge of offspring of immunized hamsters is apparently transplacental, effected either by soluble leishmanial antigen, soluble lymphocyte (or transfer) factor, or by cells.

Animals↗