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At least 1,117 records · Page 62Linked to original sources
PubMed2004

Augmentation of antitumor immune responses after adoptive transfer of bone marrow derived from donors immunized with tumor lysate-pulsed dendritic cells.

We demonstrated previously that tumor lysate-pulsed dendritic cells (TP-DC) could mediate a specific and long-lasting antitumor immune response against a weakly immunogenic breast tumor during early lymphoid reconstitution. The purpose of this study was to examine the potential therapeutic efficacy of bone marrow transplants from TP-DC-vaccinated donors. In 2 aggressive metastatic models, bone marrow transplantation with donor bone marrow cells from TP-DC-immunized mice mediated a tumor-specific immune response in the recipient, and this caused regressions of preexisting tumor metastases. After vaccination with TP-DC, donors harbored increased numbers of both activated CD4+ and CD8+ T-cell populations in the bone marrow. Adoptive transfer of T cells purified from the bone marrow of TP-DC-vaccinated mice led to a reduction in preestablished lung metastases, whereas depletion of T cells from bone marrow abolished this effect. By using T cells derived from the bone marrow of TP-DC-vaccinated major histocompatibility complex class I and class II knockout mice, the effector cells required for the observed antitumor effect were determined to be major histocompatibility complex class I-restricted CD8+ T cells. Additionally, the tumor burden in TP-DC-immunized transplant recipients could be reduced further by repetitive TP-DC immunizations after bone marrow transplantation. Collectively, these results demonstrate an important therapeutic role of bone marrow from TP-DC-immunized donors and raise the potential for this approach in patients with advanced cancer.

Adoptive Transfer↗
PubMed2002

T9 glioma cells expressing membrane-macrophage colony stimulating factor produce CD4+ T cell-associated protective immunity against T9 intracranial gliomas and systemic immunity against different syngeneic gliomas.

Cloned T9 glioma cells (T9-C2) expressing the membrane form of macrophage colony stimulating factor (mM-CSF) inoculated subcutaneously into rats do not grow and glioma-specific immunity is stimulated. Immunotherapy experiments showed that intracranial T9 tumors present for one to four days could be successfully eradicated by peripheral vaccination with T9-C2 cells. CD4+ and CD8+ T splenocytes from immunized rats, when restimulated in vitro with T9 cells, produced interleukin-2 and -4. Protective immunity against intracranial T9 gliomas could only be adoptively transferred into naive rats by the CD4+ splenocytes obtained from T9-C2 immunized rats. Rats immunized by the T9-C2 tumor cells also resisted two different syngeneic gliomas (RT2 and F98) but allowed a syngeneic NUTU-19 ovarian cancer to grow. Such cross-protective immunity against unrelated gliomas suggests that mM-CSF transfected tumor cells have immunotherapeutic potential for use as an allogeneic tumor vaccine.

Adoptive Transfer↗
PubMed2002

Genetic and immunological comparison of anti-botulinum type A antibodies from immune and non-immune human phage libraries.

Understanding the antibody response in botulinum intoxication is important for vaccine design and passive prophylaxis. To investigate this activity, we have studied the immune response to BoNT/A (botulinum neurotoxin serotype A) binding domain (HC) at the molecular level using phage display. The scFv antibodies were isolated from V-gene repertoires prepared from (a) human volunteer immunized with pentavalent botulinum toxoid and (b) non-immune human peripheral blood lymphocytes and spleenocytes. A large panel of serotype specific phage expressing botulinum binding scFv could be selected from both libraries. Epitope mapping of immune scFv binders towards BoNT/A HC revealed surprisingly a limited number of scFv recognizing conformational epitopes that corresponded to two distinct groups, clusters I and II. Only scFv from cluster I exhibited neutralizing activity in the mouse hemidiaphragm assay. Anti- BoNT/A HC clones derived from a non-immune library could be conveniently grouped into clusters III-XI and appeared to share no overlapping epitopes with cluster I or II. In addition they showed no neutralization of toxin at biologically significant concentrations. We therefore suggest that a vaccine based on the pentavalent botulinum toxoid directs the humoral immune response to a limited number of immunodominant epitopes exposed on the binding domain HC.

Antibodies, Bacterial↗
PubMed1998

Characterization of humoral immune responses induced by immunization with plasmid DNA expressing HIV-1 Nef accessory protein.

Mice immunized with plasmid DNA encoding Nef accessory protein of human immunodeficiency virus type 1 developed high levels of anti-Nef antibodies which were maintained for at least 16 months. These antibodies produced in response to Nef-expressing plasmid DNA did not recognize the linear peptides except the long C-terminal peptide for three of the ten sera. With anti-Nef antibodies produced in mice immunized with the protein Nef without any adjuvant, the same restraint epitope binding was found. On the contrary, anti-Nef antibodies from mice immunized with the protein in Freund's adjuvant showed a broader epitope reactivity pattern. Interestingly, the analysis of immunoglobulin isotype profiles of antibodies generated by the different protocols of immunization showed that plasmid DNA immunization induced predominantly IgG2a, whereas immunization with Nef protein, with or without adjuvant, yielded a preponderance of IgG1 antibodies.

Amino Acid Sequence↗
PubMed2003

The impact of the national polio immunization campaign on levels and equity in immunization coverage: evidence from rural North India.

Few studies have investigated the impact of immunization campaigns conducted under the global polio eradication program on sustainability of polio vaccination coverage, on coverage of non-polio vaccines (administered under Expanded Program on Immunization (EPI)), and on changes in social inequities in immunization coverage. This study proposes to fill the gaps in the evidence by investigating the impact of a polio immunization campaign launched in India in 1995. The study uses a before-and-after study design using representative samples from rural areas of four North Indian states. The National Family Health Survey I (NFHS I) and NFHS II, conducted in 1992-93 and 1998-99 respectively, were used as pre- and post-intervention data. Using pooled data from both the surveys, multivariate logistic regression models with interaction terms were used to investigate the changes in social inequities. During the study period, a greater increase was observed in the coverage of first dose of polio compared to three doses of polio. Moderate improvements in at least one dose of non-polio EPI vaccinations, and no improvements in complete immunization against non-polio EPI diseases were observed. The polio campaign was successful, to some extent, in reducing gender-, caste- and wealth-based inequities, but had no impact on religion- or residence-based inequities. Social inequities in non-polio EPI vaccinations did not reduce during the study period. Significant dropouts between first and third dose of polio raise concerns of sustainability of immunization coverage under a campaign approach. Similarly, little evidence to support synergy between polio campaign and non-polio EPI vaccinations raises questions about the effects of polio campaign on routine health system's functions. However, moderate success of the polio campaign in reducing social inequities in polio coverage may offer valuable insights into the routine health systems for addressing persistent social inequities in access to health care.

BCG Vaccine↗
PubMed2000

Mosquito immune responses and malaria transmission: lessons from insect model systems and implications for vertebrate innate immunity and vaccine development.

The introduction of novel biochemical, genetic, molecular and cell biology tools to the study of insect immunity has generated an information explosion in recent years. Due to the biodiversity of insects, complementary model systems have been developed. The conceptual framework built based on these systems is used to discuss our current understanding of mosquito immune responses and their implications for malaria transmission. The areas of insect and vertebrate innate immunity are merging as new information confirms the remarkable extent of the evolutionary conservation, at a molecular level, in the signaling pathways mediating these responses in such distant species. Our current understanding of the molecular language that allows the vertebrate innate immune system to identify parasites, such as malaria, and direct the acquired immune system to mount a protective immune response is very limited. Insect vectors of parasitic diseases, such as mosquitoes, could represent excellent models to understand the molecular responses of epithelial cells to parasite invasion. This information could broaden our understanding of vertebrate responses to parasitic infection and could have extensive implications for anti-malarial vaccine development.

Animals↗
PubMed1999

DNA immunization with Plasmodium falciparum serine repeat antigen: regulation of humoral immune response by coinoculation of cytokine expression plasmid.

We immunized mice with plasmid expressing the 47-kDa amino-terminal domain of the Plasmodium falciparum serine repeat antigen (SERA) using gene gun and investigated humoral immune response to SERA antigen. Significant SERA-specific IgG was observed in BALB/c mice after immunization three times with SERA expression plasmid. Furthermore, these levels were increased by the coinoculation of cytokine (IFN-gamma, IL-4, GM-CSF, or IL-12) expression plasmid. In respect to the SERA-specific Ig subclasses, coinoculation of IFN-gamma, GM-CSF, or IL-12 expression plasmid increased the levels of SERA-specific IgG2a, and these were much higher than that in mice immunized with SERA expression plasmid alone. In contrast to the SERA-specific IgG2a, coinoculation of any cytokine expression plasmid did not change the levels of SERA-specific IgG1. These results indicate that cytokine expression plasmid enhances and regulates humoral immune response elicited by SERA DNA immunization.

Animals↗
PubMed1999

Comparison of antibody and protective immune responses against Trypanosoma cruzi infection elicited by immunization with a parasite antigen delivered as naked DNA or recombinant protein.

Immunization with naked DNA represents an attractive strategy for development of vaccines against a variety of infections including those caused by protozoan parasites. Recently, we have described that immunization with a plasmid containing the trans-sialidase (TS) gene induced protective immunity against Trypanosoma cruzi infection in BALB/c mice. The present study was aimed at examining and comparing the effectiveness of immunization using either plasmid or recombinant delivered antigens in a mouse strain highly susceptible to infection (A/Sn). Two plasmids were generated containing the coding region for the catalytic domain of TS. TS gene was inserted into pcDNA3 vector with or without the coding region for TS signal peptide. These two plasmids were found to be equally immunogenic at inducing antibodies to TS or inhibition of T. cruzi infection. A third plasmid, in which the TS gene was inserted into the vector VR1012, was as immunogenic as the two others. Immunization with a TS recombinant protein in alum generated a significantly higher antibody response as measured by ELISA or inhibition of TS enzymatic activity. Most relevant, this immunization reduced the mortality due to acute infection.

Animals↗
PubMed1998

Models of immune memory: on the role of cross-reactive stimulation, competition, and homeostasis in maintaining immune memory.

There has been much debate on the contribution of processes such as the persistence of antigens, cross-reactive stimulation, homeostasis, competition between different lineages of lymphocytes, and the rate of cell turnover on the duration of immune memory and the maintenance of the immune repertoire. We use simple mathematical models to investigate the contributions of these various processes to the longevity of immune memory (defined as the rate of decline of the population of antigen-specific memory cells). The models we develop incorporate a large repertoire of immune cells, each lineage having distinct antigenic specificities, and describe the dynamics of the individual lineages and total population of cells. Our results suggest that, if homeostatic control regulates the total population of memory cells, then, for a wide range of parameters, immune memory will be long-lived in the absence of persistent antigen (T1/2 > 1 year). We also show that the longevity of memory in this situation will be insensitive to the relative rates of cross-reactive stimulation, the rate of turnover of immune cells, and the functional form of the term for the maintenance of homeostasis.

Animals↗
PubMed1985

Rheumatoid factor (RF) production during anamnestic immune responses in the mouse. III. Activation of RF precursor cells is induced by their interaction with immune complexes and carrier-specific helper T cells.

IgG1 immune complexes were identified as the humoral stimuli responsible for the synthesis of IgG1-specific IgM rheumatoid factor (RF), which occurs in the mouse during the early stages of secondary immune responses to protein antigens. The specificity of this phenomenon was illustrated by the fact that complexes made with IgG1 F(ab')2 fragments or with antibodies of a different isotype failed to induce significant anti-IgG1 RF synthesis. The importance of immune complexes in the induction of RF was further underscored by the substantial increase in the titers of isotype-specific RF observed in the serum of mice immunized with IgG1- or IgG2a-complexed antigen rather than with antigen alone. The RF-inducing capacity of the complexes varied with the antigen/antibody ratio: it was maximal in antibody excess or at equivalence, but dramatically reduced in large antigen excess. The importance of T cell priming in RF precursor cell activation by immune complexes was demonstrated by the failure of T cell-deprived spleen cells to reconstitute the capability of irradiated mice to produce RF, and by the optimal RF responses observed after reconstitution of irradiated recipients with primed T cells and naive B cells. The involvement of T cells in this process could not be explained by the release of nonspecific B cell activators, because antigenic stimulation of primed T cells failed to enhance the activation of RF precursor cells by immune complexes of unrelated antigen.

Animals↗
PubMed1995

Implicating a role for immune recognition of self in tumor rejection: passive immunization against the brown locus protein.

The immune system can recognize differentiation antigens that are selectively expressed on malignant cells and their normal cell counterparts. However, it is uncertain whether immunity to differentiation antigens can effectively lead to tumor rejection. The mouse brown locus protein, gp75 or tyrosinase-related protein 1, is a melanocyte differentiation antigen expressed by melanomas and normal melanocytes. The gp75 antigen is recognized by autoantibodies and autoreactive T cells in persons with melanoma. To model autoimmunity against a melanocyte differentiation antigen, mouse antibodies against gp75 were passively transferred into tumor-bearing mice. Passive immunization with a mouse monoclonal antibody against gp75 induced protection and rejection of both subcutaneous tumors and lung metastases in syngeneic C57BL/6 mice, including established tumors. Passive immunity produced coat color alterations but only in regenerating hairs. This system provides a model for autoimmune vitiligo and shows that immune responses to melanocyte differentiation antigens can influence mouse coat color. Immune recognition of a melanocyte differentiation antigen can reject tumors, providing a basis for targeting tissue autoantigens expressed on cancer.

Animals↗
PubMed2003

Vaccine immunity to pathogenic fungi overcomes the requirement for CD4 help in exogenous antigen presentation to CD8+ T cells: implications for vaccine development in immune-deficient hosts.

Systemic fungal infections with primary and opportunistic pathogens have become increasingly common and represent a growing health menace in patients with AIDS and other immune deficiencies. T lymphocyte immunity, in particular the CD4+ Th 1 cells, is considered the main defense against these pathogens, and their absence is associated with increased susceptibility. It would seem illogical then to propose vaccinating these vulnerable patients against fungal infections. We report here that CD4+ T cells are dispensable for vaccine-induced resistance against experimental fungal pulmonary infections with two agents, Blastomyces dermatitidis an extracellular pathogen, and Histoplasma capsulatum a facultative intracellular pathogen. In the absence of T helper cells, exogenous fungal antigens activated memory CD8+ cells in a major histocompatibility complex class I-restricted manner and CD8+ T cell-derived cytokines tumor necrosis factor alpha, interferon gamma, and granulocyte/macrophage colony-stimulating factor-mediated durable vaccine immunity. CD8+ T cells could also rely on alternate mechanisms for robust vaccine immunity, in the absence of some of these factors. Our results demonstrate an unexpected plasticity of immunity in compromised hosts at both the cellular and molecular level and point to the feasibility of developing vaccines against invasive fungal infections in patients with severe immune deficiencies, including those with few or no CD4+ T cells.

Animals↗
PubMed1999

Nasal immunization induces Haemophilus influenzae-specific Th1 and Th2 responses with mucosal IgA and systemic IgG antibodies for protective immunity.

To determine the efficacy of a mucosal vaccine against nontypeable Haemophilus influenzae (NTHi), mice were immunized nasally, orally, intratracheally, or intraperitoneally with NTHi antigen together with cholera toxin. Antigen-specific IgA antibody titers in nasal washes and the numbers of antigen-specific IgA-producing cells in nasal passages showed the greatest increases in mice immunized nasally. Cytokine analysis showed that interferon-gamma, interleukin (IL)-2, IL-5, IL-6, and IL-10 were induced by nasal immunization, suggesting that Th2- and Th1-type cells were generated. Furthermore, bacterial clearance of a homologous strain of NTHi from the nasal tract was significantly enhanced in the nasal immunization group. These findings suggest that nasal immunization is an effective vaccination regimen for the induction of antigen-specific mucosal immune responses, which reduce the colonization of NTHi in the nasal tract.

Animals↗
PubMed2001

Protective anti-Helicobacter immunity is induced with aluminum hydroxide or complete Freund's adjuvant by systemic immunization.

To determine whether systemic immunization against Helicobacter pylori could be achieved with an adjuvant approved for human use, the efficacy of vaccination with Helicobacter antigen in combination with aluminum hydroxide (AlOH) was evaluated in a murine model of Helicobacter infection. Immunization with antigen and AlOH induced interleukin-5-secreting, antigen-specific T cells, and immunization with antigen and complete Freund's adjuvant induced interferon-gamma-secreting, antigen-specific T cells, as determined by ELISPOT assay. Both immune responses conferred protection after challenge with either H. pylori or H. felis, as confirmed by the complete absence of any bacteria, as assessed by both histology and culture of gastric biopsy samples. Protection was antibody independent, as demonstrated with antibody-deficient muMT mice (immunoglobulin-gene knockout mice), and CD4(+) spleen T cells from immunized mice were sufficient to transfer protective immunity to otherwise immunodeficient rag1(-/-) recipients. These results suggest an alternative and potentially more expeditious strategy for development of a human-use H. pylori vaccine.

Adoptive Transfer↗
PubMed2002

Potent, persistent cellular immune responses elicited by sequential immunization of rhesus macaques with Ad5 host range mutant recombinants encoding SIV Rev and SIV Nef.

Vaccines incorporating multiple HIV components should elicit broad immunity and protection against a spectrum of HIV strains. Early regulatory and accessory gene products are attractive candidates for such vaccines. Here, immunogenicity studies on SIV Rev and Nef expressed in replication competent Adenovirus type 5 host range mutant vectors (Ad5hr) are summarized. Interferon-gamma (IFN-gamma)-secreting cells in response to Env and Rev peptides were enumerated by ELISPOT after two sequential immunizations of 55 macaques with Ad5hr-SIVenv/rev. Responses to SIV Nef were assessed in 16 macaques also immunized with Ad5hr-SIVnef. Potent cellular immunity to both Rev and Nef was induced following the second Ad-recombinant immunization and persisted for at least 30 weeks. Persistent cellular immunity to SIV Env was also seen, with a mean of 700 IFN-gamma-secreting cells per million PBMC. Rev and Env responses were positively correlated. While greater responses to early gene products occur in natural infection, as immunogens Rev and Nef elicited the same number of IFN-gamma secreting cells as Env, after adjusting for differences in protein size. The same percentage of macaques also responded to Rev, Nef, and Env: 59, 63, and 64%, respectively. Overall, Ad5hrSIVenv/rev and -SIVnef were highly effective immunogens. Their contribution to protective efficacy will be addressed in future studies.

AIDS Vaccines↗
PubMed1998

Comparative analysis of humoral immune responses to HIV type 1 envelope glycoproteins in mice immunized with a DNA vaccine, recombinant Semliki Forest virus RNA, or recombinant Semliki Forest virus particles.

The Semliki Forest virus (SFV) system seems to be a useful new approach for generating effective immune responses against HIV-1 in animal models. We evaluated this system by comparing the humoral immune responses raised in mice immunized against the HIV-1 envelope with the SFV system, a DNA vaccine, and a recombinant Env glycoprotein. gp160 ELISA antibody titers (204,800) were highest in the sera from mice immunized with recombinant Semliki Forest virus particles. These sera contained antibodies to the CD4-binding site and recognized linear epitopes on gp120 and gp41 that were also recognized by a pool of sera from HIV1-infected individuals. This demonstrates that the HIV-1 envelope produced in vivo by the SFV system does not fold aberrantly. A low level of neutralizing antibodies against the HIV-1LAI strain was also detected in the serum of one mouse immunized with recombinant SFV particles, suggesting that booster injections should be given to achieve a more effective immune response. SFV recombinant particles induced the strongest humoral responses to the HIV-1 envelope of all the potential HIV env vaccines tested.

AIDS Vaccines↗
PubMed1998

Inhibitory effect of lipopolysaccharide on immune response after DNA immunization is route dependent.

The DNA prepared from E. coli contained high levels of lipopolysaccharide (LPS). When antigen-encoding DNA was injected into mice, toxicity and increased IgM responses were observed. A method for purifying high yields of DNA (up to 12 mg/L of broth culture) with very low levels of LPS (0.05 ng/mg) was developed. When this purified DNA was used for immunization studies, the toxicity and increased IgM responses were abrogated. Thus, LPS was added to DNA in order to examine its influence on the IgG and cytotoxic T lymphocyte (CTL) response after intramuscular (i.m.) or intradermal (i.d.) DNA immunization. The IgG response to DNA-encoded antigen was inhibited in a dose-dependent manner by the i.d., but not the i.m., route of immunization. Surprisingly, no effect on the CTL response was observed. Therefore, the ability to produce high yields of plasmid DNA with very low levels of endotoxin contamination is advantageous for DNA immunization studies, not only for toxicologic but also for immunologic considerations. Furthermore, these results provide further evidence that immune induction occurs via different mechanisms after i.m. and i.d. DNA immunization.

Animals↗
PubMed1993

Long-term persistence of sterile immunity in a volunteer immunized with X-irradiated Plasmodium falciparum sporozoites.

Three volunteers were immunized by repeated exposure to the bites of Plasmodium falciparum-infected, X-irradiated mosquitoes to characterize immunologic responses and duration of protective immunity. A primary series of immunizations had been shown previously to induce sterile immunity in these volunteers against sporozoite-induced P. falciparum malaria. In the current study, antibodies to sporozoites circulated at high levels for at least 9-12 months after the volunteers were administered booster bites from X-irradiated infective mosquitoes. One volunteer challenged a second time with P. falciparum 9 months after his last immunization was again shown to be protected, whereas all 5 control subjects developed patent infections. These results set a new standard for persistence of sterile immunity against experimental P. falciparum infection.

Adult↗