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At least 1,189 records · Page 66Linked to original sources
PubMed2004

Immunologic studies of specific mucosal and systemic immune responses in Mexican school children after booster aerosol or subcutaneous immunization with measles vaccine.

The purpose of the present study was to compare serum and mucosal immune responses following either aerosol (Aer) or subcutaneous (SQ) measles immunization of Mexican school children. A cohort of 49 children from 6 to 7 years of age received either Aer ( n = 22) or SQ ( n = 27) Edmonston-Zagreb (EZ) measles vaccine. Serum and nasal secretions were collected prior to (Pre), 1 and 3 months (mos) intervals and analyzed for immunoglobulin (Ig) concentrations and measles specific Ig isotype-associated antibody by enzyme immunoassay (EIA). Serum and nasal IgG and IgA antibody responses were stimulated following immunization with live, attenuated EZ measles vaccine administered either by SQ or Aer routes but these responses were significantly greater by the Aer compared to the SQ route. These studies also suggest that the level of antibody in these secretions may serve as an important marker of immunity to measles and lend further support for aerosol immunization as an effective alternative vaccine delivery strategy for measles eradication.

Administration, Intranasal↗
PubMed2004

Oral immunization of piglets with recombinant F4 fimbrial adhesin FaeG monomers induces a mucosal and systemic F4-specific immune response.

The importance of adhesins in the pathogenicity of several bacteria resulted in studies on their usefulness in vaccines. In this study, the gene of the F4(K88)-fimbrial adhesin FaeG of the pathogenic enterotoxigenic Escherichia coli (ETEC) strain GIS26 was cloned in the pET30Ek-LIC vector and expressed with an N-terminal His- and S-tag in the cytoplasm of BL21(DE3). Recombinant FaeG (rFaeG) subunits were isolated from insoluble cytoplasmic aggregates and refolded into a native-like F4 receptor (F4R)-binding conformation. Indeed, the presence of conformational epitopes was shown by ELISA and the ability to bind the F4R was observed by inhibiting the adhesion of F4+ ETEC to F4R+ villi with increasing concentrations of native-like refolded rFaeG subunits. The rFaeG subunits appear as monomers, whereas the purified F4 fimbriae are multimers. Oral immunization of newly weaned piglets with native-like rFaeG induced a mucosal and systemic F4-specific immune response, significantly reducing F4+ E. coli excretion from 2 till 5 days following challenge infection. However, improvement of stability and immunogenicity of rFaeG is necessary since a higher F4-specific response was obtained following immunization with purified F4 fimbriae. Furthermore, the N-terminal fusion of a His- and S-tag was not detrimental for binding the F4R, supporting the use of FaeG as mucosal carrier. In conclusion, oral immunization with a recombinant fimbrial adhesin subunit of Escherichia coli induces a mucosal and systemic fimbriae-specific immune response.

Adhesins, Bacterial↗
PubMed2005

Systemic mobilization of antigen presenting cells, with a chimeric Flt-3 and G-CSF receptor agonist, during immunization of Macaca mulatta with HIV-1 antigens is insufficient to modulate immune responses or vaccine efficacy.

In order to improve the efficacy of current vaccine candidates against HIV/AIDS, we sought to strengthen the induction of immune responses via simultaneous in vivo mobilization of dendritic cells using a chimeric Flt-3 and G-CSF receptor agonists (ProGP). We investigated ProGP treatment in combination with two DNA immunizations encoding HIV-Env89.6, SIV-Gag proteins to increase the priming of immune responses. Administration of this Flt-3/G-CSF chimera elicited marked increases in numbers of both plasmacytoid and myeloid dendritic cells. However, there was no increase seen in T-cell responses either directly following the DNA immunization or after further boosting with MVA vectors expressing HIV-Env89.6p, SIV-Gag. After challenge with SHIV89.6p all animals became infected and no differences were seen between the ProGP treated versus the control group with regard to plasma virus load or CD4 T-cell count. We conclude that besides mobilization of dendritic cells additional stimuli to induce dendritic cell maturation may be needed for avid boosting of antigen specific immune activation.

AIDS Vaccines↗
PubMed2006

Induction of protective and mucosal immunity against diphtheria by a immune stimulating complex (ISCOMS) based vaccine.

There is increasing concern over the efficacy of existing vaccines for diphtheria and there is interest in the development of a mucosally active formulation which might improve local protection. Lipophilic immune stimulating complexes (ISCOMS) containing Quil A are active by both parenteral and mucosal routes and here we have established methods for incorporating palmitified diphtheria toxoid (DT) into ISCOMS. The resulting formulation was immunogenic by the subcutaneous, oral and intranasal routes, with very low doses of DT inducing systemic humoral immune responses, as well as cell mediated immunity including both gammaIFN and IL5 production. Intranasal immunisation with DT in ISCOMS also stimulated significant local antibody production in tracheal washes, as well as cellular immunity in draining lymphoid tissues and serum neutralising antibodies. Finally, subcutaneous immunisation of guinea pigs with DT in ISCOMS primed protective immunity against challenge with diphtheria holotoxin more efficiently than the equivalent doses of DT in the conventional alum vaccine. ISCOMS based vaccines may provide a novel strategy for mucosal and systemic immunisation against diphtheria.

Adjuvants, Immunologic↗
PubMed2006

Nasal immunization with a dual antigen anthrax vaccine induced strong mucosal and systemic immune responses against toxins and bacilli.

Anthrax-vaccine-adsorbed (AVA), the only anthrax vaccine licensed in the U.S., suffers from many major drawbacks. Therefore, there is a need to develop new generation anthrax vaccines that can be easily administered and induce strong immune responses not only against the anthrax toxins, but also against the toxin-producing vegetative anthrax bacilli. In the present study, we evaluated the feasibility of inducing strong mucosal and systemic immune responses against both anthrax toxins and bacilli after nasal immunization using a synthetic double-stranded RNA (dsRNA), polyriboinosinic-polyribocytidylic acid (poly(I:C) or pI:C), as the adjuvant. We have shown that the capsular poly-gamma-D-glutamic acid (PGA) from bacillus was immunogenic when conjugated to a carrier protein and dosed intranasally to mice. We further demonstrated that nasal immunization with the PGA-carrier protein conjugate in combination with the anthrax protective antigen (PA) protein induced both anti-PGA and anti-PA immune responses in mouse sera and lung mucosal secretions. The anti-PA antibody (Ab) response was shown to have anthrax lethal toxin neutralization activity; and the anti-PGA Abs induced were able to activate complement and kill PGA-producing bacteria. These findings demonstrated that it is feasible to develop a novel dual-action nasal anthrax vaccine.

Adjuvants, Immunologic↗
PubMedDate not supplied

Respective roles of immune and nutritional factors in the priming of the immune response in the elderly.

Ninety-six institutionalized elderly (greater than 70 years old) (mean age: 82 +/- 7 years) subjects, negative for tetanus toxoid antibodies were primed with tetanus toxoid vaccination and dinitrochlorobenzene (DNCB). Correlations were studied between some immunological parameters, nutritional parameters prior to immunization and the immune response intensity after it. Levels of tetanus toxoid specific IgG (ELISA assay) were positively correlated with monocyte phagocytosis, DNCB response and prealbumin levels, and negatively correlated with total IgG, monocyte immune degradation and tetanus toxoid lymphocyte stimulation. No correlation was observed with IgA, IgM, PHA stimulation. Tetanus toxoid lymphocyte stimulation correlated positively with response to DNCB, and negatively with tetanus toxoid IgG as well as total IgG. DNCB response correlated with prealbumin, tetanus toxoid IgG and tetanus toxoid lymphocyte stimulation. Therefore, it appears that malnutrition, as measured by prealbumin level, is one of the main factors contributing to the inconstant senile immunodeficiency. Monocyte antigenic degradation function unaltered with age can impair immune response while conserved or increased phagocytosis enhances immune response in the elderly. High total IgG levels were linked with low specific responses to priming antigens. High specific antibody levels also correlated negatively with cellular specific response. It is assumed that regulatory IgG antibody accumulation, likely anti-idiotypic antibodies, play an important role in senile immunological depletion.

Aged↗
PubMed1998

The immune system can affect learning: chronic immune complex disease in a rat model.

Evidence is presented that the immune system can affect central nervous system functioning, leading to changes in learning. Immune complex disease is induced in rats and their behavior tested using a Lashley maze. Significant differences in behavior were found between the animals with high disease activity and those with low disease activity and the non-disease controls. These changes were not due to uremia and are most likely due to the immune response. There is some evidence immune complex deposits in the choroid plexus may play some role, but not the sole or major role in the behavioral changes. This provides a model by which immunologic processes can cause neuropsychiatric manifestations in autoimmune diseases like lupus, as well as showing that immune processes can affect behavioral functioning.

Animals↗
PubMed1998

Universal hepatitis B immunization: infant, and infant plus adolescent immunization.

Hepatitis B virus (HBV) is one of the world's most widespread infectious agents and the cause of millions of diseases and deaths each year. Vaccination programmes aimed at risk groups are important for individual protection, but will not eliminate viral transmission in Europe, since 70% of acute hepatitis B cases are either acquired by sexual activity or are of unknown origin. In industrialized countries, HBV infection occurs mainly in young adults, however, when the virus is acquired during infancy it leads to extremely high rates of chronic carriership, contributing disproportionately to the overall pool of HBsAg carriers. This explains why integrating universal HB vaccination into routine infant immunization programmes is the best means for controlling HB in countries with intermediate to high levels of HB endemicity. In countries of low endemicity, universal immunization of adolescents may be considered as an alternative to infant vaccination, as this strategy has a more rapid effect on the epidemiology of the infection. Where feasible, a double strategy (infant plus adolescent) is the optimal solution. With this strategy, adolescent immunization is necessary only for the time required for the first cohort of immunized infants to reach adolescence. After universal vaccination programmes have been implemented, efforts must be made to sustain vaccine procurement, monitor coverage, check the incidence of acute disease, particularly in immunized cohorts and verify by seroepidemiological studies the progression made in the elimination of HBV transmission.

Adolescent↗
PubMed1998

CpG DNA, a novel immune enhancer for systemic and mucosal immunization with influenza virus.

Bacterial DNA causes B cell proliferation, immunoglobulin secretion, and Th1-like cytokine secretion, due to unmethylated CpG dinucleotides in particular base contexts (CpG motifs), which are far more common in bacterial DNA than in vertebrate DNA. Synthetic oligodeoxynucleotides (ODN) containing CpG motifs also trigger immune activation, suggesting possible utility as vaccine enhancers. Mice systemically primed with formalin-inactivated influenza virus mixed with CpG ODN, generated virus-specific serum antibodies at titres approximately seven times higher than mice immunized without CpG; the titres were further increased following an identical second injection. To determine whether CpG could be absorbed through mucosae and enhance vaccination responses, mice were immunized intranasally (IN) with the same preparation of virus with or without CpG ODN or Escherichia coli DNA. Following IN immunization, CpG ODN or E. coli DNA promoted increased production of influenza-specific antibodies in serum, saliva and the genital tract, compared with the control groups. These studies indicate that stimulatory CpG ODN are promising new immune enhancers for vaccination applications.

Administration, Intranasal↗
PubMed1996

Can we find a solution to the human immunodeficiency virus/acquired immune deficiency syndrome controversy? Is acquired immune deficiency syndrome the consequence of continuous excessive stressing of the body?

The time of re-evaluation of the role of human immunodeficiency viruses in the pathogenesis of acquired immune deficiency syndrome has now come, now that methods are available for the direct detection of human immunodeficiency viruses and for the detection of cellular anti-human immunodeficiency virus immune reactions. It has been shown that human immunodeficiency virus infections are common among anti-human immunodeficiency virus antibody negative high-risk individuals. The disease is brought under control by cellular immune reactions and the anti-human immunodeficiency virus antibody test remains negative. Apart from proof that infection with human immunodeficiency viruses has occurred, a positive result in an anti-human immunodeficiency virus-antibody test is also an indication of an independent immunosuppression state. According to the definition of the Centers of Disease Control classical acquired immune deficiency syndrome is the consequence of infection with human immunodeficiency virus in association with continuous excessive stress, such as observed in the known risk groups. At the center of the pathogenetic process is hypercortisolism-determined damage of T lymphocytes, in which insufficiency of thymus is prominent. For this reason, in our view, there are indications for shifting efforts from the prophylaxis of infection with human immunodeficiency viruses to the prophylaxis of acquired immune deficiency syndrome by reducing stress factors.

Acquired Immunodeficiency Syndrome↗
PubMed2004

Immune system paralysis by anthrax lethal toxin: the roles of innate and adaptive immunity.

Since the deliberate use of anthrax as a bioweapon in the USA in 2001, an enormous amount of attention has been focused on the biology of Bacillus anthracis, the causative bacterium of anthrax. Fatal systemic anthrax involves massive bacteraemia and toxaemia with non-descript early symptoms until the onset of shock and sudden death. The outbreak of fatal symptoms after the incubation period of B anthracis suggests an impairment of the host immune system against this pathogen. Thus, it is likely that B anthracis will possess certain strategies to escape from the host immune system. However, the mechanisms of such immune-evasion strategies are not fully characterised yet. Given the critical role of B anthracis toxins in anthrax pathogenesis, much effort has been made to understand the pathological nature of the toxins. Recent studies have shown the pleiotropic actions of anthrax lethal toxin on host innate immune cells, and that several effects of anthrax lethal toxin may directly account for the mechanism of immune intervention by B anthracis.

Animals↗
PubMed1972

Specific enhancement of transplantation immunity with heat-killed Mycobacterium butyricum and immunizing extracts from adenovirus 12-induced tumour cells.

Transplant immunity to adenovirus 12-induced tumour cells was demonstrated in CBA mice which had been previously immunized with extracts of homologous tumour cells. Immunization of mice with tumour cell extract together with heat-killed Mycobacterium butyricum gave better transplant immunity to tumour cell challenge than tumour extracts alone. Mice immunized with Mycobacterium butyricum alone prior to challenge with tumour cells, did not show any significant difference in the incidence of tumours from control mice.

Adenoviridae↗
PubMed1998

Mucosal immunization with HIV-1 peptide vaccine induces mucosal and systemic cytotoxic T lymphocytes and protective immunity in mice against intrarectal recombinant HIV-vaccinia challenge.

Mucosal tissues are major sites of HIV entry and initial infection. Thus, the induction of a mucosal cytotoxic T lymphocyte (CTL) response is an important feature for an effective HIV vaccine. However, little is known about approaches to induce such a protective CTL response in the mucosa. Here for the first time we show that intrarectal immunization with a synthetic, multideterminant HIV peptide plus cholera toxin adjuvant induced long-lasting, antigen-specific CTL memory in both the inductive (Peyer's patch) and effector (lamina propria) mucosal sites, as well as in systemic sites (spleen), whereas systemic immunization induced specific CTL only in the spleen. Cholera toxin adjuvant, while enhancing the response, was not essential. The CTL recognized target cells either pulsed with HIV peptide or expressing endogenous whole envelope glycoprotein of Mr 160,000 (gp160). Exploring the requirements for CTL induction, we show that mucosal CTL responses are both interleukin 12 and interferon-gamma dependent by using antibody-treated and knock-out mice. Finally, to determine whether a mucosal response is actually protective against local mucosal challenge with virus, we show that intrarectal immunization with the synthetic HIV peptide vaccine protected mice against infection via mucosal challenge with a recombinant vaccinia virus expressing HIV-1IIIB gp160. These studies provide an approach to development of an HIV vaccine that induces CTL immunity in the mucosal and systemic immune systems and protects against mucosal infection with a virus expressing HIV-1 gp160.

AIDS Vaccines↗
PubMed1982

Evaluation of the immune response to type III pneumococcal polysaccharide as a means to evaluate T-independent immune function in the rat.

Since the rat is frequently the experimental animal of choice for toxicology testing, studies were undertaken to adapt assays routinely used to evaluate immune function in mice so that immune function could likewise be evaluated in collaborative projects employing toxicant-treated rats. Contrary to previous reports in the literature, Type III pneumococcal polysaccharide (S3) was immunogenic in rats. Specific antibody responses to S3 were demonstrated in two strains of rats following immunization by either the subcutaneous (sc) or intraperitoneal (ip) route with purified S3, with S3 contained in polyvalent pneumococcal polysaccharide vaccine (pneumovax), or with heat-killed Type III Streptococcus pneumoniae. Dose-response studies demonstrated that the optimal immunizing dose in Sprague-Dawley or Fischer rats was 25 micrograms S3. Reimmunization with S3 on d 21 did not produce an anamnestic response, and the kinetic data were consistent with S3 being a thymus-independent (T-independent) antigen in the rat. In contrast to our previous studies in the mouse, concurrent sc or ip injections of pertussis vaccine did not modify the response to S3 in rats. Sprague-Dawley rats acquired the capacity to respond immunologically to S3 between 24 and 31 d of age. In mature animals, sex had no effect on the ability to respond to S3. The utility of this model as a means of characterize toxicant-induced immune dysfunction was demonstrated using the prototype immunotoxicant cyclo-phosphamide.

Aging↗
PubMed2001

Humoral immune-mediated acute, antigen-induced arthritis in rats is suppressed by the inducing antigen administered orally before, but not after, immunization.

Acute ovalbumin-induced arthritis (OIA), which is mediated by Arthus reaction to ovalbumin (OVA) in the joint space, can be induced by immunization of rats with OVA followed by the intraarticular injection of OVA. Because oral administration of antigen induces immunological unresponsiveness, we studied for the first time the effects of oral administration of OVA on acute OIA. The oral administration of OVA before immunization significantly suppressed the development of acute OIA, in accordance with decreases in both the anti-OVA IgG antibody production and in vitro lymphocyte proliferative responses to OVA. However, the oral administration of OVA after immunization did not show any decrease in antibody production or in vitro lymphocyte proliferation to OVA, or in the severity of acute OIA. These results indicate that the induction of oral tolerance to OVA in OIA is possible by oral administration of OVA before, but not after, immunization with the antigen. This supports the concept of using antigen feeding as a treatment for certain humoral immune-mediated diseases.

Acute Disease↗
PubMed1975

Genetic control of specific immune suppression. II. H-2-linked dominant genetic control of immune suppression by the random copolymer L-glutamic acid50-L-tyrosine50 (GT).

Several inbred as well as congenic resistant strains of mice, which fail to respond to the random copolymer of L-glutamic acid50-L-tyrosine50 (GT), were shown to develop specific PFC responses when stimulated by GT complexed to an immunogenic carrier such as methylated bovine serum albumin (MBSA). In these studies we have found that GT preimmunization has a tolerogenic effect on the response to GT-MBSA in some mouse strains; whereas in other strains of mice, GT fails to inhibit the GT-MBSA response. We may, therefore, conclude that immune suppression cannot account for nonresponsiveness in all cases. The development of specific immune suppression in response to GT was shown to be inherited as a dominant trait in F1 hybrids resulting from the mating of suppressor with nonsuppressor strains. This trait is, therefore, under the control of a gene or genes that we have designated as specific immune suppression gene(s) Is genes. The strain distribution of GT induced suppression demonstrates that Is genes are coded for in the H-2 complex. Furthermore, immune suppression by the two related copolymers, GT and GAT, are distinct in different strains of mice. The significance of these data for our understanding of the regulation of the immune response is discussed.

Alanine↗
PubMed1991

Protective humoral immune responses to the human immunodeficiency virus induced in immunized pigs: a possible source of therapeutic immunoglobulin preparations.

The human immunodeficiency virus (HIV-1) induces progressive and fatal disease in infected hosts. Initially the human immune response appears to control HIV infection. This hypothesis is supported by the long latency period observed during HIV infection prior to development of the active disease state. Similarly the observation of fetal protection from HIV infection in some pregnant women who have high titered neutralizing antibody responses to the virus underscores the importance of the humoral response to HIV in limiting infection. Therefore antibody replacement therapy is likely to provide substantial clinical benefits in this and other infected populations. However, currently there is no safe source for human antibodies with the desired protective qualities necessary for passive immune therapies. For a passive immune therapy to be valid it must protect against a diverse collection of viral isolates. Such a task is likely to require a complex mixture of human antibodies or human substitute antibodies which are available in large quantities and target conserved regions of the viral envelope, such that protection from diverse isolates are realized. Porcine products have been used extensively in many human therapeutic replacement regimens. Their use is primarily due to genetic similarity of the two species at the amino acid level which results in a high acceptance of grafted prosthetics and excellent tolerance of repeatedly administered biologicals. Accordingly we have examined the immunoglobulin responses to the Human Immunodeficiency Virus (HIV-1) of the Yorkshire mixed breed pig. Immunized animals developed significant humoral immunity as judged by ELISA, Western blot, radioimmunoprecipitation, flow microfluorimetry as well as in functional assays including neutralization and syncytia inhibition. The high neutralizing activity obtained and the immunological similarity between human and porcine immunoglobulin suggests that further investigation into the use of porcine immunoglobulin as human replacement antibodies for the therapeutic treatment of HIV is warranted.

Animals↗
PubMed1994

Humoral, mucosal, and cellular immune response to topical immunization with a subunit respiratory syncytial virus vaccine.

The efficacy of topical immunization with the respiratory syncytial virus (RSV) fusion (F) protein was tested in mice using cholera toxin B chain (CTB) as an adjuvant. The dose of CTB required for the adjuvant effect (as measured by local and systemic antibody stimulation) and protection from viral challenge was > or = 5 micrograms. With this dose, mice immunized intranasally with CTB plus F protein were highly protected from viral replication in the upper and lower respiratory tract. This protection was associated with the induction of mucosal IgA and serum IgG and neutralizing antibody. Addition of parenteral immunization with F protein to the topical vaccination provided protection from viral challenge nearly equivalent to immunization with live RSV intranasally. Topical and parenteral immunization with F protein was not associated with induction of splenic cytotoxic T cells, in contrast to live virus given intranasally.

Adjuvants, Immunologic↗