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At least 1,549 records · Page 86Linked to original sources
PubMed1992

Direct evidence that primary acquired cell-mediated immunity is less resistant than is primary thymus-dependent humoral immunity to the depressive influence of wasting protein-energy malnutrition in weanling mice.

Wasting protein-energy malnutrition (PEM) was induced in male C57BL/6J mice fed a low-protein diet ad libitum from 23 to 37 d of age. In comparison with a complete diet, the low-protein formulation reduced delayed hypersensitivity to sheep red blood cells (SRBCs) assessed on day 14 of feeding by measuring increased footpad thickness (mean +/- SD: 4 +/- 4% vs 22 +/- 8%, P less than 0.01), after immunization on day 9, and after challenge with SRBCs on day 13. By contrast, the low-protein diet did not affect the anti-SRBC hemagglutinin titer (8.3 +/- 2.2 vs 9.1 +/- 1.1, P greater than 0.30) despite profound reduction in numbers of splenic plasma cells secreting IgM-class anti-SRBCs (7.3 +/- 3.1 vs 49.9 +/- 23.8 x 10(-3), P less than 0.001), after immunization on day 9 and assessment on day 14. Thus, direct experimental evidence, previously altogether lacking, is provided in support of the concept, central to nutritional immunology, that acquired cell-mediated immunity is less resistant than is systemic humoral immunity to the depressive influence of pre-adolescent, wasting PEM.

Animals↗
PubMed2002

The sustainability of hepatitis B immunization within the Universal Immunization Programme in India.

Based on the recommendations of the World Health Organization, India as a member-state is likely to implement universal immunization against hepatitis B through the existing Universal Immunization Programme (UIP). A pilot project is already under progress in two municipal zones of Delhi. This paper begins by reviewing epidemiological features of hepatitis B in India, some established aspects and other emerging trends. The gaps in the existing knowledge base are also given due consideration. The current recommendation is to deliver the vaccine at zero-day for infants in the absence of facilities for antenatal screening and immunoglobulin administration. The paper explores the potential pitfalls for integrating the proposed hepatitis B vaccination with the DPT (diphtheria/pertussis/tetanus) schedule. Based on the findings of the National Family Health Survey, the likely coverage for the states is estimated for both the schedules--zero-day and with DPT. The performance of the pilot phase is reviewed through the results of a coverage survey. The paper also estimates the resources that should be committed to launch the universal immunization of hepatitis B vaccination and the sustainability issues thereof. The paper finally concludes with the position that hepatitis B immunization will 'sink or sail' with the UIP. Further, this should act as an engine for recharging the infrastructure and functioning of the public health system and promote general preventive practices like universal precautions.

Diphtheria-Tetanus-Pertussis Vaccine↗
PubMed1979

Experimental syphilis in the rabbit: passive transfer of immunity with immunoglobulin G from immune serum.

A preparation of immunoglobulin G isolated from a pool of immune sera derived from rabbits with long-term syphilis was shown to possess a high degree of purity as judged by immunodiffusion and protein electrophoresis. The antitreponemal power of the preparation of immunoglobulin G and that of the immune serum pool from which it was derived were found to be equivalent in both the skin protection and the systemic protection test. The observation that neither normal serum nor a pool of serum derived from animals "immunized" with Salmonella typhi, Escherichia coli, Streptococcus pyogenes, or zymosan was protective indicates that the protective power of the immune serum studied was due to specific antibodies residing principally, if not entirely, in the immunoglobulin G fraction of the serum.

Animals↗
PubMed1995

Lombok Hepatitis B Model Immunization Project: toward universal infant hepatitis B immunization in Indonesia.

The Lombok Hepatitis B (HB) Model Immunization Project was the first mass infant HB immunization project in Indonesia. Key aspects were the procurement of low-cost HB vaccine, integration into routine infant immunization services, and delivery of the first dose in the home within 1 week of birth. The project achieved > 90% coverage with 3 doses of vaccine. The prevalence of HB surface antigen was 1.4% in infants who received 3 doses (with the first dose within 7 days of birth) and 3.0% in those who received the first dose > 7 days after birth, compared with a baseline prevalence of 6.2% (P < .001 in each case). Most vaccine failures occurred in children born to HBe antigen-positive mothers. Antibody prevalence and titers did not correlate with protection. HB vaccine can be successfully integrated into the Expanded Programme on Immunization (EPI), strengthening the EPI and significantly reducing chronic HB infection.

BCG Vaccine↗
PubMed2007

Innate immunity mediated by epidermal keratinocytes promotes acquired immunity involving Langerhans cells and T cells in the skin.

Skin is an immunological organ consisting of epidermal cells, i.e. keratinocytes and Langerhans cells (LCs, antigen-presenting dendritic cells), and both innate and acquired immune systems operate upon exposure of the skin to various external microbes or their elements. To explore the relationship between innate and acquired immunities in the skin, we investigated whether Toll-like receptor (TLR) ligation of epidermal cells enhances the ability of LCs to present a specific antigen to T cells in mice. LC-containing epidermal cells were incubated with CpG oligonucleotide (TLR9 ligand) modified with trinitrophenyl hapten, and cultured with hapten-primed CD4(+) T cells. TLR9 ligand was capable of enhancing the hapten-presenting ability of LCs when LC-enriched epidermal cells, but not purified LCs, were used as the LC source, suggesting that bystander keratinocytes play a role in the enhancement of LC function. Cultivation of freshly isolated epidermal cells with CpG promoted the expression of major histocompatibility complex (MHC) class II and CD86 molecules on LCs. CpG enhanced the production of interleukin (IL)-1alpha, granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumour necrosis factor (TNF)-alpha by primarily cultured keratinocytes. The addition of a cocktail of neutralizing antibodies against these cytokines abrogated the CpG-promoted, antigen-presenting ability of LC-enriched epidermal cells. Moreover, the addition of culture supernatants from CpG-stimulated keratinocytes restored the ability of purified LCs. Our study demonstrated that although the direct effect of CpG on LCs is minimal, LC function can be up-regulated indirectly by cytokines released by CpG-stimulated keratinocytes. This also implies that innate immunity evoked by TLR ligation of keratinocytes enhances acquired immunity comprising LCs and T cells.

Animals↗
PubMed2005

Induction and recall of immune memory by mucosal immunization with a non-toxic recombinant enterotoxin-based chimeric protein.

Previous reports have suggested that peroral delivery of antigens chemically coupled to non-toxic recombinant enterotoxin B subunits, such as the cholera toxin B subunit (CTB), induces tolerance to the antigen that may be abrogated by the toxic enzyme activity of intact enterotoxins, such as cholera toxin (CT). The aim of this study was to examine the immunogenicity of a genetically coupled protein composed of the saliva-binding region (SBR) of the Streptococcus mutans surface antigen AgI/II and the non-toxic A2 and B subunits of CT (SBR-CTA2/B) compared with that of recombinant SBR admixed with CT (SBR + CT) and SBR chemically coupled to recombinant CTB (SBR-CTB) following peroral delivery by intragastric (i.g.) immunization. The results showed that i.g. immunization with SBR-CTA2/B, like SBR + CT, induced antigen-specific serum immunoglobulin G (IgG) and salivary IgA antibodies, and sensitized splenic T cells. Comparison studies with SBR-CTB produced serum IgG but not salivary IgA titres and failed to sensitize splenic cells. Immunization with SBR-CTA2/B via the intranasal route also primed for the recall of antigen-specific memory antibody responses 6 months later. These findings show that SBR-CTA2/B is an immunogenic, not tolerogenic, chimeric protein that can induce and recall antigen-specific memory responses upon mucosal immunization.

Adjuvants, Immunologic↗
PubMed1984

T cell-mediated immunity in murine malaria. II. Induction of protective immunity to P. chabaudi by antigen-fed macrophages and antigen-educated lymphocytes.

We previously described assay systems for generating antigen specific proliferating T cells to P. chabaudi antigens. In the present study we examine whether the various sensitization approaches confer immunity against a cloned virulent strain IP-PCI of P. chabaudi. We present data indicating that effective specific protective immunity can be induced through P. chabaudi antigen fed macrophages and antigen educated spleen cells (initiator lymphocytes). The expression of this protective immunity is proposed to depend on (a) antigen presentation and/or accessory function of macrophages and (b) the subsequent activation of T cell functions related to protection. Indeed analysis of different macrophage populations revealed a correlation between the expression of Ia molecules and IL-1 secretion with their capacity to induce antigen specific T cells in vivo and subsequent protective immune mechanisms. Thus these results emphasize the critical functions of accessory cells in determining the outcome of malaria infections.

Animals↗
PubMed1976

Control of the immune response: role of macrophages in regulation of antibody-and cell-mediated immune responses.

The ability of peritoneal macrophage subpopulations, separated into different classes according to their size, to reconstitute antibody or cellular immune responses in macrophage-depleted spleen cells has been investigated. Data are presented to show that whether reconstitution is by "normal" or "activated" macrophages, be they syngeneic or allogeneic to the lymphocyte source, different populations reconstitute antibody and cellular immunity. Reconstitution is in general by two classes of macrophages, small and large. The former seem to reconstitute only if syngeneic to the responding lymphocyte pool, whereas large macrophages reconstitute immune responses from allogeneic lymphocytes as well as syngeneic lymphocytes. Evidence is also presented to show that syngeneic large macrophages can determine the type of immune response reconstituted; that is, with greater numbers of large cells only cytotoxic responses (and not T-dependent antibody formation) were reconstituted and vice versa.

Animals↗
PubMed2001

Priming of immune responses to hepatitis B surface antigen in young mice immunized in the presence of maternally derived antibodies.

Early vaccination is necessary to protect infants from various infectious diseases. However, this is often unsuccessful largely due to the immaturity of the neonatal immune system. Furthermore, maternally derived antibodies can interfere with active immunization. We have previously shown in young mice that immune responses against several different antigens can be improved by the addition of oligodeoxynucleotides containing immunostimulatory CpG motifs (CpG ODN). In this study we have evaluated immunization of newborn (1-7-day-old) BALB/c mice against hepatitis B surface antigen (HBsAg), with alum and/or CpG ODN, in the presence of high levels of maternal antibody against HBsAg (anti-HBs). Seroconversion rates and anti-HBs titers were compared to those induced by a HBsAg-expressing plasmid, since other studies had suggested DNA vaccines to be superior to protein vaccines in young mice with maternal antibody. HBsAg/alum/CpG ODN was superior to DNA vaccine in inducing HBsAg-specific CTL responses in young mice in the presence of maternally transferred anti-HBs antibodies. However, B cell responses to both HBsAg/alum/CpG ODN and DNA vaccines remained weak in the presence of maternally transferred anti-HBs antibodies.

Adjuvants, Immunologic↗
PubMed1996

The instructive role of innate immunity in the acquired immune response.

Innate immunity has been considered only to provide rapid, incomplete antimicrobial host defense until the slower, more definitive acquired immune response develops. However, innate immunity may have an additional role in determining which antigens the acquired immune system responds to and the nature of that response. Knowledge of the molecules and pathways involved may create new therapeutic options for infectious and autoimmune diseases.

Animals↗
PubMed1978

Protective immunity induced in mice by immunization with high-molecular-weight polysaccharide from Pseudomonas aeruginosa.

A high-molecular-weight alkali-labile polysaccharide (PS) isolated from the slime of immunotype 1 Pseudomonas aeruginosa was tested for its ability to protect mice from lethal challenge with the live, homologous organism. Intraperitoneal (i.p.) injection of 10 to 25 microgram of the PS protected 60 to 70% of the mice against challenge with up to 50 50% lethal dose units. Although single immunization of mice with up to 250 microgram of PS effected protective levels of only 70%, two successive immunizations provided 100% protection. Subcutaneous and intravenous immunization with PS also provided protection to i.p. challenges with immunotype 1 P. aeruginosa, but not to i.p. challenge with immunotype 4 P. aeruginosa. Although lipopolysaccharide (LPS) was found to be more immunogenic than PS in out studies, contamination of the alkali-labile PS with LPS did not account for the protection seen. Alkali treatment (0.1 N NaOH, 37 degrees C, 2 h) of the PS destroyed its protective effectiveness, while similarly treated LPS retained its capacity for inducing immunity in mice. Adsorption and passive protection studies with sera raised to either PS or a mixture of PS and LPS indicated that antibody directed to the alkali-labile PS antigen was capable of contributing to the protection of mice against challenge with P. aeruginosa.

Animals↗
PubMed1995

Mice immunized by primary vaginal Candida albicans infection develop acquired vaginal mucosal immunity.

It has been postulated that systemic cell-mediated immunity (CMI) is an important host defense mechanism against Candida infections of the vagina. However, in an estrogen-dependent murine model of experimental vaginal candidiasis, we recently showed that systemic Candida-specific Th1-type CMI induced by immunization with Candida culture filtrate antigen had no effect on vaginal Candida population levels during the course of a vaginal infection. In the present study, mice given a second vaginal inoculation in the presence of peripheral Candida-specific Th1-type CMI induced by prior vaginal infection had anamnestic-type increased delayed-type hypersensitivity (DTH) responses, concomitant with significantly fewer Candida organisms in the vagina than in primary-infected mice. In addition, organisms in secondary-infected mice were fragmented and superficial penetration into the epithelium was reduced. The systemic presence of Candida-specific T suppressor (Ts) cells that significantly suppressed the infection-derived anamnestic DTH reactivity did not abrogate the protective effect in the vagina. Additional experiments showed that vaginally immunized mice were not protected from gastrointestinal or systemic candidiasis and, in contrast to mice with a second vaginal infection, did not demonstrate anamnestic DTH reactivity. These results suggest that a moderate level of local protection against a Candida vaginal infection can be achieved by vaginal immunization but that the protective role of acquired peripheral Candida-specific Th1-type reactivity at the vaginal mucosa appears to be limited.

Animals↗
PubMed1998

Oral immunization with a Salmonella typhimurium vaccine vector expressing recombinant enterotoxigenic Escherichia coli K99 fimbriae elicits elevated antibody titers for protective immunity.

Bovine enterotoxigenic Escherichia coli (ETEC) continues to cause mortality in piglets and newborn calves. In an effort to develop a safe and effective vaccine for the prevention of F5(+) ETEC infections, a balanced lethal asd+ plasmid carrying the complete K99 operon was constructed and designated pMAK99-asd+. Introduction of this plasmid into an attenuated Salmonella typhimurium Deltaaro Deltaasd strain, H683, resulted in strain AP112, which stably expresses E. coli K99 fimbriae. A single oral immunization of BALB/c and CD-1 mice with strain AP112 elicited significant mucosal immunoglobulin A (IgA) titers that remained elevated for >11 weeks. IgA and IgG responses in serum specific for K99 fimbriae were also induced, with a prominent IgG1, as well as IgG2a and IgG2b, titer. To assess the derivation of these antibodies, a K99 isotype-specific B-cell ELISPOT analysis was conducted by using mononuclear cells from the lamina propria of the small intestines (LP), Peyer's patches (PP), and spleens of vaccinated and control BALB/c mice. This analysis revealed elevated numbers of K99 fimbria-specific IgA-producing cells in the LP, PP, and spleen, whereas elevated K99 fimbria-specific IgG-producing cells were detected only in the PP and spleen. These antibodies were important for protective immunity. One-day-old neonates from dams orally immunized with AP112 were provided passive protection against oral challenge with wild-type ETEC, in contrast to challenged neonates from unvaccinated dams or from dams vaccinated with a control Salmonella vector. These results confirm that oral Salmonella vaccine vectors effectively deliver K99 fimbriae to mucosal inductive sites for sustained elevation of IgA and IgG antibodies and for eliciting protective immunity.

Animals↗
PubMed2003

Immunization with cDNA expressed by amastigotes of Trypanosoma cruzi elicits protective immune response against experimental infection.

Immunization of mice with plasmids containing Trypanosoma cruzi genes induced specific antibodies, CD4(+) Th1 and CD8(+) Tc1 cells, and protective immunity against infection. In most cases, plasmids used for DNA vaccination contained genes encoding antigens expressed by trypomastigotes, the nonreplicative forms of the parasite. In this study, we explored the possibility of using genes expressed by amastigotes, the form of the parasite which replicates inside host cells, for experimental DNA vaccination. For that purpose, we selected a gene related to the amastigote surface protein 2 (ASP-2), an antigen recognized by antibodies and T cells from infected mice and humans, for our study. Using primers specific for the asp-2 gene, four distinct groups of genes were amplified from cDNA from amastigotes of the Y strain of T. cruzi. At the nucleotide level, they shared 82.3 to 89.9% identity with the previously described asp-2 gene. A gene named clone 9 presented the highest degree of identity with the asp-2 gene and was selected for immunological studies. Polyclonal antisera raised against the C terminus of the recombinant protein expressed by the clone 9 gene reacted with an antigen of approximately 83 kDa expressed in amastigotes of T. cruzi. Immunization of BALB/c mice with eukaryotic expression plasmids containing the clone 9 gene elicited specific antibodies and CD4(+) T-cell-dependent gamma interferon secretion. Upon challenge with trypomastigotes, mice immunized with plasmids harboring the clone 9 gene displayed reduced parasitemia and survived lethal infection. We concluded that amastigote cDNA is an interesting source of antigens that can be used for immunological studies, as well as for vaccine development.

Amino Acid Sequence↗
PubMed2004

Mucosally delivered Salmonella live vector vaccines elicit potent immune responses against a foreign antigen in neonatal mice born to naive and immune mothers.

The development of effective vaccines for neonates and very young infants has been impaired by their weak, short-lived, and Th-2 biased responses and by maternal antibodies that interfere with vaccine take. We investigated the ability of Salmonella enterica serovars Typhi and Typhimurium to mucosally deliver tetanus toxin fragment C (Frag C) as a model antigen in neonatal mice. We hypothesize that Salmonella, by stimulating innate immunity (contributing to adjuvant effects) and inducing Th-1 cytokines, can enhance neonatal dendritic cell maturation and T-cell activation and thereby prime humoral and cell-mediated immunity. We demonstrate for the first time that intranasal immunization of newborn mice with 10(9) CFU of S. enterica serovar Typhi CVD 908-htrA and S. enterica serovar Typhimurium SL3261 carrying plasmid pTETlpp on days 7 and 22 after birth elicits high titers of Frag C antibodies, previously found to protect against tetanus toxin challenge and similar to those observed in adult mice. Salmonella live vectors colonized and persisted primarily in nasal tissue. Mice vaccinated as neonates induced Frag C-specific mucosal and systemic immunoglobulin A (IgA)- and IgG-secreting cells, T-cell proliferative responses, and gamma interferon secretion. A mixed Th1- and Th2-type response to Frag C was established 1 week after the boost and was maintained thereafter. S. enterica serovar Typhi carrying pTETlpp induced Frag C-specific antibodies and cell-mediated immunity in the presence of high levels of maternal antibodies. This is the first report that demonstrates the effectiveness of Salmonella live vector vaccines in early life.

Administration, Intranasal↗
PubMed2006

Toll-like receptor adaptor molecules enhance DNA-raised adaptive immune responses against influenza and tumors through activation of innate immunity.

Toll-like receptors (TLRs) recognize microbial components and trigger the signaling cascade that activates the innate and adaptive immunity. TLR adaptor molecules play a central role in this cascade; thus, we hypothesized that overexpression of TLR adaptor molecules could mimic infection without any microbial components. Dual-promoter plasmids that carry an antigen and a TLR adaptor molecule such as the Toll-interleukin-1 receptor domain-containing adaptor-inducing beta interferon (TRIF) or myeloid differentiation factor 88 (MyD88) were constructed and administered to mice to determine if these molecules can act as an adjuvant. A DNA vaccine incorporated with the MyD88 genetic adjuvant enhanced antigen-specific humoral immune responses, whereas that with the TRIF genetic adjuvant enhanced cellular immune responses. Incorporating the TRIF genetic adjuvant in a DNA vaccine targeting the influenza HA antigen or the tumor-associated antigen E7 conferred superior protection. These results indicate that TLR adaptor molecules can bridge innate and adaptive immunity and potentiate the effects of DNA vaccines against virus infection and tumors.

Adaptor Proteins, Signal Transducing↗
PubMed2002

Immunization with surface antigen vaccine alone and after treatment with 1-(2-fluoro-5-methyl-beta-L-arabinofuranosyl)-uracil (L-FMAU) breaks humoral and cell-mediated immune tolerance in chronic woodchuck hepatitis virus infection.

Woodchucks chronically infected with the woodchuck hepatitis virus (WHV) were treated with the antiviral drug 1-(2-fluoro-5-methyl-beta-L-arabinofuranosyl)-uracil (L-FMAU) or placebo for 32 weeks. Half the woodchucks in each group then received four injections of surface antigen vaccine during the next 16 weeks. Vaccination alone elicited a low-level antibody response to surface antigen in most carriers but did not affect serum WHV DNA and surface antigen. Carriers treated first with L-FMAU to reduce serum WHV DNA and surface antigen and then vaccinated had a similar low-level antibody response to surface antigen. Following vaccinations, cell-mediated immunity to surface antigen was demonstrated in both groups, independent of serum viral and antigen load, but was significantly enhanced in woodchucks treated with L-FMAU and was broadened to include other viral antigens (core, e, and x antigens and selected core peptides). Cell-mediated immunity and antibody responses to surface antigen were observed after drug discontinuation in half of the carriers that received L-FMAU alone. Surface antigen vaccine alone or in combination with drug broke humoral and cell-mediated immune tolerance in chronic WHV infection, but the combination with drug was more effective. This suggested that a high viral and antigen load in carriers is important in maintaining immunologic tolerance during chronicity. The humoral and cellular immunity associated with the combination of L-FMAU and vaccine resembled that observed in self-limited WHV infection. Such combination therapy represents a potentially useful approach to the control of chronic hepatitis B virus infection in humans.

Animals↗
PubMed2006

A novel adenovirus type 6 (Ad6)-based hepatitis C virus vector that overcomes preexisting anti-ad5 immunity and induces potent and broad cellular immune responses in rhesus macaques.

Success in resolving hepatitis C virus (HCV) infection has been correlated to vigorous, multispecific, and sustained CD8(+) T-cell response in humans and chimpanzees. The efficacy of inducing T-cell-mediated immunity by recombinant serotype 5 adenovirus vector has been proven in many animal models of infectious diseases, but its immunogenicity can be negatively influenced by preexisting immunity against the vector itself. To evaluate the less prevalent adenovirus serotype 6 (Ad6) as an alternative vector for and HCV vaccine development, we have generated serotype 5 and 6 adenoviral vectors directing expression of the nonstructural region of HCV (MRKAd5-NSmut and MRKAd6-NSmut). Immunogenicity studies in mice showed that the two vectors induced comparable T-cell responses but that only MRKAd6-NSmut was not suppressed in the presence of anti-Ad5 immunity. In contrast, preexisting anti-Ad5 immunity dramatically blunted the immunogenicity of the serotype 5-based HCV vector. Furthermore, MRKAd6-NSmut showed equivalent potency, breadth, and longevity of HCV-specific T-cell responses in rhesus macaques as the corresponding Ad5-based vector over a wide range of doses and was capable of boosting DNA-primed animals even if administered at low doses. These data support the use of the MRKAd6-NSmut for anti-HCV immunotherapy and, more generally, for the Ad6 serotype as a better genetic vaccine vehicle than Ad5.

Adenoviridae↗