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Results for “Immune correlation”

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At least 217 records · Page 12Linked to original sources

PubMed1999

IL-5 dominates cytokine responses during expression of protective immunity to Onchocerca lienalis microfilariae in mice.

In a model of protective immunity against Onchocerca microfilariae (mf), it has been demonstrated previously that immunocompetent mice clear a primary infection and are highly resistant to re-infection. This immunity correlates with CD4+ Th2 cells, is dependent on IL-5 but not IL-4, and can be transferred adoptively with spleen cells. In the current investigation, high levels of spontaneous proliferation and of IFN gamma production were observed in splenocyte cultures from immune mice, compared with cells from naive controls. Antigen-specific proliferation also occurred in immune cells, being vigorous following stimulation with adult worm antigen, but not with antigens from developing embryos or mf. Levels of IL-4, IL-5 and IFN gamma induced by the various antigens was similar, indicating that activation of alternate T helper cell sub-sets was unlikely to explain the lack of cellular responsiveness. After a primary inoculation with mf, spleen cells from infected mice co-produced IFN gamma and IL-5. In contrast, IFN gamma production was downregulated while IL-5 levels remained high during active elimination of a challenge infection. Significant levels of IL-4 production occurred only once parasite clearance had begun. These data confirm the importance of IL-5 in protection against Onchocerca mf in mice and question the role of IFN gamma in the expression of immunity. Production of high levels of IL-5 correlated with blood and tissue eosinophil mobilization during the clearance of a challenge infection.

Animals↗

PubMed1994

Bacterial immunogens and protective immunity in swine.

This review provides a limited discussion of antibody-mediated immune responses to bacterial pathogens which cause disease in swine. Serum antibody titers or responses have been used to correlate immunization or convalescence with protection from a given disease or infectious agent. Though much effort has been devoted to the elucidation of the host's antibody response to bacterial antigens, there are limited examples where an antibody response to a singular antigen has induced protection from disease. Antibody responses have been shown to be very effective in neutralizing bacterial exotoxins, e.g. Escherichia, Pasteurella, Actinobacillus, and inhibiting the ability of bacterial pathogens to colonize mucosal surfaces, e.g. Escherichia, Salmonella. The protective role of monospecific antibody responses to other bacterial components are less clear; however, antibody responses are generally polyclonal in nature and are an important component of the host immune response following the onset of disease. Anticapsular antibodies have been shown to enhance phagocytosis of numerous pathogens, e.g. Actinobacillus, Streptococcus, Pasteurella. Humoral immune responses directed against the lipopolysaccharide (LPS) of many Gram-negative organisms have been shown to enhance phagocytosis and the activation of complement, e.g. Salmonella. Anti-LPS antibodies have also aided in the identification of the serotypic diversity of Gram-negative organisms, e.g. Serpulina, Salmonella, Pasteurella. Antibody responses to the outer membrane proteins of Gram-negative organisms enhance phagocytosis, activation of complement, or inhibit bacterial adhesion to host cell. Adhesion of Gram-positive microorganisms, e.g. Staphylococcus, Streptococcus, Clostridium, to eukaryotic cells can be inhibited by antibody against the peptidoglycan and these peptidoglycan-specific antibodies may also facilitate opsonization of these organisms. Mycoplasma species have been shown to be metabolically inhibited by antibody directed against membrane proteins. In addition to the protective aspects of humoral immunity, the host's antibody response has been used as a diagnostic and epidemiological tool to identify or determine the prevalence of infectious agents.

Animals↗

PubMed1977

Immunity to experimental cholera. III. Enhanced duration of protection after sequential parenteral-oral administration of toxoid to dogs.

Protection against experimental cholera after immunization with a purified glutaraldehyde toxoid given subcutaneously (sc), orally, or by a combined sc-oral sequence was compared in dogs. The protection induced by toxoid appeared to be entirely due to antitoxin. Repeated sc immunization with precipitated toxoid resulted in 77% protection at two weeks but no protection at four months. Protection after sc immunization correlated with titers of antitoxin in serum and appeared to result entirely from serum-derived antibody. In contrast, immunization by the sc-oral sequence resulted in prolonged protection (74% at two weeks, P=0.04; 100% after four months, P=0.004; and 57% after eight months, P=0.01) that was not related to the low serum antitoxin titers achieved. This sequence was effective only if the oral booster was given in divided doses. Immunization by oral priming and boosting was ineffective. These results suggest that the sc-oral sequence of immunization is an efficient means of stimulating the enteric immune response to nonreplicating protein antigens and may provide an improved approach to immunization against cholera.

Administration, Oral↗

PubMed2005

[Increased IL-4 production in response to virulent Mycobacterium tuberculosis in tuberculosis patients with advanced disease].

The study was designed to compare immune responses to Mycobacterium tuberculosis bacilli and antigens in healthy Portuguese subjects and pulmonary tuberculosis patients (TB), and to correlate immune status with clinical severity of tuberculosis disease. PBMC were cultured and stimulated with live and killed M. tuberculosis H37Rv and purified protein derivative (PPD) and lymphoproliferation and production of IFN-gamma and IL-5/IL-4 by these cultures were evaluated by the use of ELISA and multi-parameter flow cytometry. PBMC from 30 tuberculosis patients demonstrated significantly reduced amounts of proliferation and IFN-gamma when stimulated with live M. tuberculosis compared the control group. Of 15 tuberculosis patients tested for intracellular IL-4 following stimulation with M. tuberculosis, 7 showed greatly increased IL-4 production in CD8+ and gammadelta+ T cells. Tuberculosis patients demonstrated an increase of intracellular IL-4 after PBMC were stimulated with live M. tuberculosis in the CD4+ phenotype, but more notably in CD8+ and gammadelta TCR+ subsets. Increased production of IL-4 in tuberculosis patients was primarily in individuals with advanced involvement of lung parenchymal with high bacterial loads in sputum. These results suggest that an alteration in type 1 and type 2 cytokine balance can occur in patients with tuberculosis at an advanced clinical stage of disease.

Adult↗

PubMed2002

Promises and pitfalls in the reconstitution of immunity in patients who have HIV-1 infection.

Recent studies suggest that immunologic containment of HIV-1 is possible and the immune correlates of this control are being defined. There have been significant advances in our ability to elicit virus-specific immune responses, which have led to viral control in animal models. Although viral escape from the immune system is an important challenge, new strategies for therapeutic and preventative HIV-1 vaccination are being vigorously pursued in human trials.

AIDS Vaccines↗

PubMed2005

Oral spore vaccine based on live attenuated nontoxinogenic Bacillus anthracis expressing recombinant mutant protective antigen.

An attenuated nontoxinogenic nonencapsulated Bacillus anthracis spore vaccine expressing high levels of recombinant mutant protective antigen (PA), which upon subcutaneous immunization provided protection against a lethal B. anthracis challenge, was found to have the potential to serve also as an oral vaccine. Guinea pigs immunized per os with the recombinant spore vaccine were primed to B. anthracis vegetative antigens as well as to PA, yet only a fraction of the animals (30% to 50%) mounted a humoral response to all of these antigens. Protective immunity provided by per os immunization correlated with a threshold level of PA neutralizing antibody titers and was long-lasting. Protection conferred by per os immunization was attained when the vaccine was administered in the sporogenic form, which, unlike the vegetative cells, survived passage through the gastrointestinal tract. A comparison of immunization of unirradiated spores with immunization of gamma-irradiated spores demonstrated that germination and de novo synthesis of PA were prerequisites for mounting an immune protective response. Oral immunization of guinea pigs with attenuated B. anthracis spores resulted in a characteristic anti-PA immunoglobulin isotype profile (immunoglobulin [G1 IgG1] versus IgG2), as well as induction of specific anti-PA secretory IgA, indicating development of mucosal immunity.

Administration, Oral↗

PubMed2004

HIV viral shedding in semen: lack of correlation with systemic virus-specific CD8 responses.

Semen is a major transmission vector for HIV. Virus-specific CD8 T cells are critical in HIV control, but their relationship with semen viral load is unknown. We therefore examined the association between systemic HIV-specific IFN-gamma CD8 responses and viral load in the semen and blood of HIV-infected men. No correlation was observed between viral load in either semen or blood and systemic CD8 T-cell responses. Further studies of immune correlates of semen HIV shedding are needed.

CD8-Positive T-Lymphocytes↗

PubMed1995

The dermatophytes.

The etiologic agents of the dermatophytoses (ringworm) are classified in three anamorphic (asexual or imperfect) genera, Epidermophyton, Microsporum, and Trichophyton. Species capable of reproducing sexually belong in the teleomorphic genus, Arthroderma, of the Ascomycota. On the basis of primary habitat association, they may be grouped as geophilic (soil associated), zoophilic, and anthropophilic. Adaptation to growth on humans by most geophilic species resulted in diminished loss of sporulation, sexuality, and other soil-associated characteristics. The dermatophytes have the ability to invade keratinized tissue (skin, hair, and nails) but are usually restricted to the nonliving cornified layer of the epidermis because of their inability to penetrate viable tissue of an immunocompetent host. However, invasion does elicit a host response ranging from mild to severe. Acid proteinases, elastase, keratinases, and other proteinases reportedly act as virulence factors. The development of cell-mediated immunity correlated with delayed hypersensitivity and an inflammatory response is associated with clinical cure, whereas the lack of or a defective cell-mediated immunity predisposes the host to chronic or recurrent dermatophyte infection. Chronic dermatophytosis is mostly caused by Trichophyton rubrum, and there is some evidence that mannan produced by this fungus suppresses or diminishes the inflammatory response. Since dermatophytes cause a communicable disease, modes of transmission and control are discussed as well as a survey of recent trends in therapy. Collection of specimens, culture media, and tests for identification are also presented. Genetic studies have led to an understanding of incompatibility mechanisms, pleomorphism and variation, resistance to griseofulvin, and virulence. Molecular biology has contributed to our knowledge of the taxonomy and phylogenetic relationships of dermatophytes.

Antigens, Fungal↗

PubMed2007

T cell immune responses to HIV-1.

The recent use of multiparametric flow cytometry to monitor T cell immune responses complements traditional assays, such as IFN-gamma ELISPOT, to provide more information on the functional complexity of CD4+ and CD8+ T cell immune responses induced either by natural infection, or by immunization. In this review, we provide a general background on T cell subsets, and describe the cellular immune response during natural HIV-1 infection. We then review T cell responses to current candidate HIV-1 vaccines. Taken together, this helps to formulate our understanding of the immune correlates of protection required for an effective prophylactic HIV-1 vaccine. Finally, we emphasize current dendritic cell based vaccine strategies designed to modulate immunity to establish immune protection against HIV-1.

AIDS Vaccines↗

PubMed2002

Interferon-alpha in tumor immunity and immunotherapy.

Interferon-alpha (IFN-alpha) is a pleiotropic cytokine belonging to type I IFN, currently used in cancer patients. Early studies in mouse tumor models have shown the importance of host immune mechanisms in the generation of a long-lasting antitumor response to type I IFN. Recent studies have underscored new immunomodulatory effects of IFN-alpha, including activities on T and dendritic cells, which may explain IFN-induced tumor immunity. Reports on new immune correlates in cancer patients responding to IFN-alpha represent additional evidence on the importance of the interactions of IFN-alpha with the immune system for the generation of durable antitumor response. This knowledge, together with results from studies on genetically modified tumor cells expressing IFN-alpha, suggest novel strategies for using these cytokines in cancer immunotherapy and in particular the use of IFN-alpha as an immune adjuvant for the development of cancer vaccines.

Animals↗

PubMed2003

A review of human papillomavirus vaccines: from basic science to clinical trials.

Human papillomavirus (HPV) infection leads to a spectrum of disease from genital warts to precancerous lesions to cervical and anal cancer and is a worldwide public health problem of epidemic proportions. Unique to HPV-related neoplasia, the presence of specific viral antigens such as the L1 capsid structural protein and the oncoproteins E6 and E7 provide opportunities for vaccine therapy. Although difficult to precisely define, the natural immune response to HPV is vitally important and defects in cell mediated immunity correlate with increased risk of disease and cancer. In preclinical animal models, both prophylactic and therapeutic vaccines have effectively induced HPV-specific cell mediated immune responses protecting animals from viral challenge or eliminating established tumors. Most prophylactic vaccines are virus-like particles (VLP) composed of the L1 structural protein. Phase I trials have demonstrated safety and immunogenicity, but limited efficacy data are available. Therapeutic vaccine trials are reviewed including E6 and E7 vaccines comprised of peptides, fusion proteins, encapsulated plasmid DNA, and recombinant vaccinia virus. All of the vaccines appear to be safe, well tolerated, and preliminary data indicates that most are clinically effective. Multiple trials are in progress and more mature data are expected within the next few years.

Animals↗

PubMed1999

Induction of protective host immunity to carcinoembryonic antigen (CEA), a self-antigen in CEA transgenic mice, by immunizing with a recombinant vaccinia-CEA virus.

Human carcinoembryonic antigen (CEA) is a well-characterized oncofetal glycoprotein whose overexpression by human carcinomas has been a target for cancer immunotherapy. Transgenic mice that express CEA as a self-antigen with a tissue distribution similar to that of humans have been developed. This study investigates: (a) the responsiveness of the CEA transgenic (CEA.Tg) mice to endogenous CEA or CEA administered as a whole protein in adjuvant; and (b) whether the presentation of CEA as a recombinant vaccinia virus could generate CEA-specific host immunity. By and large, the CEA.Tg mice were unresponsive to CEA, as shown by the lack of detectable CEA-specific serum antibodies and the inability to prime an in vitro splenic T-cell response to CEA. Furthermore, the administration of whole CEA protein in adjuvant to CEA.Tg mice failed to elicit either anti-CEA IgG titers or CEA-specific T-cell responses. Only weak anti-CEA IgM antibody titers were found in those mice. In contrast, CEA.Tg mice immunized with recombinant vaccinia virus expressing CEA generated relatively strong anti-CEA IgG antibody titers and demonstrated evidence of immunoglobulin class switching. These mice also developed T(H)1-type CEA-specific CD4+ responses and CEA peptide-specific cytotoxicity. The ability to generate CEA-specific host immunity correlated with protection of the CEA.Tg mice against a challenge with CEA-expressing tumor cells. Protection against tumor growth was accomplished with no apparent immune response directed at CEA-positive normal tissue. The results demonstrate the ability to generate an effective antitumor immune response to a tumor self-antigen by immunization with a recombinant vaccinia virus. CEA.Tg mice should be an excellent experimental model to study the effects of more aggressive immunization schemes directed at established tumors with the possible development of accompanying autoimmune responses involving normal tissues.

Animals↗

PubMed2006

Comparative analysis of T-cell turnover and homeostatic parameters in HIV-infected patients with discordant immune-virological responses to HAART.

OBJECTIVE: Inadequate CD4 cell count recovery despite full HIV RNA control occurs in 30% of HAART-treated HIV-infected patients. A better understanding of the relationship between T-cell dynamics and the HIV intracellular reservoir in HIV-infected patients failing to recover CD4 cell count following long-term HAART, is required. METHODS: In a cross-sectional study T-cell turnover and homeostatic parameters featuring discordant responses were investigated in 27 immunologic non-responders (INR; CD4 count, < or = 200 cells/microl; HIV RNA, < or = 50 copies/ml), 15 virological non-responders (VNR; CD4 count, > or = 350 cells/microl; HIV RNA, > or = 10 000) and 22 full responders (FR; CD4 count, > or = 500 cells/microl; HIV RNA, < or = 50 copies/ml). RESULTS: INR displayed significantly higher activated CD38CD8 than FR (P < 0.05) and was comparable to VNR (P > 0.05). As compared with VNR and FR, INR displayed the highest level of proliferating Ki67CD4 and apoptotic CD4 cells (P < 0.05). VNR presented lower proliferation and apoptosis than FR and INR. INR displayed the lowest levels of naive T cells (P < 0.05) and a predominant memory pattern. Despite the memory/activated/apoptotic phenotype, INR showed a statistically non-significant reduction in T-cell receptor excision circles (TREC) compared to FR (P > 0.05), and substantially heightened interleukin (IL)-7 (P < 0.05), while VNR showed higher naive T-cell counts and TREC. Moreover, the reservoir of infected CD4 cells was increased in INR, with a trend toward highest intracellular HIV DNA within total, naive and memory CD4 cells. CONCLUSIONS: The lack of CD4 cell count recovery in INR seems to reflect a highly activated apoptotic T-cell compartment, with elevated IL-7 and thymic impairment. High levels of intracellular HIV-DNA in INR could be strictly involved in the lack of T-cell reconstitution. Immune correlates of an ultimate direction of the response to HAART, could be exploited in clinical practice for the most effective management of discordant patients, to amend immune imbalances and to improve clinical outcome.

Adult↗

PubMed2006

Why can't the immune system control HIV-1? Defining HIV-1-specific CD4+ T cell immunity in order to develop strategies to enhance viral immunity.

Globally, at least 60 million people have been infected with the human immunodeficiency virus type 1 (HIV-1), the majority of whom will develop the acquired immunodeficiency syndrome (AIDS) leading to tremendous morbidity and the mortality. Understanding the immunopathogenesis of AIDS and the immune correlates of viral protection are necessary to develop effective vaccines and immunotherapies. A major focus of our laboratory has been to understand the CD4+ T cell immune response directed against HIV- 1, and to determine mechanisms of T cell dysfunction that lead to viral escape. In addition, we are interested in evaluating the TNF-TNFR family members as potential molecular adjuvants that could be incorporated into vaccines which could be used to further boost T cell immunogenicity in healthy or HIV-1-infected individuals, as many of these molecules have been shown to replace the functions of CD4+ T cell help.

AIDS Vaccines↗

PubMed2003

Protection from lethal infection is determined by innate immune responses in a mouse model of Ebola virus infection.

A mouse-adapted strain of Ebola Zaire virus produces a fatal infection when BALB/cj mice are infected intraperitoneally (ip) but subcutaneous (sc) infection with the same virus fails to produce illness and confers long-term protection from lethal ip rechallenge. To identify immune correlates of protection in this model, we compared viral replication and cytokine/chemokine responses to Ebola virus in mice infected ip (10 PFU/mouse), or sc (100 PFU/mouse) and sc "immune" mice rechallenged ip (10(6) PFU/mouse) at several time points postinfection (pi). Ebola viral antigens were detected in the serum, liver, spleen, and kidneys of ip-infected mice by day 2 pi, increasing up to day 6. Sc-infected mice and immune mice rechallenged ip had no detectable viral antigens until day 6 pi, when low levels of viral antigens were detected in the livers of sc-infected mice only. TNF-alpha and MCP-1 were detected earlier and at significantly higher levels in the serum and tissues of ip-infected mice than in sc-infected or immune mice challenged ip. In contrast, high levels of IFN-alpha and IFN-gamma were found in tissues within 2 days after challenge in sc-infected and immune mice but not in ip-infected mice. Mice became resistant to ip challenge within 48 h of sc infection, coinciding with the rise in tissue IFN-alpha levels. In this model of Ebola virus infection, the nonlethal sc route of infection is associated with an attenuated inflammatory response and early production of antiviral cytokines, particularly IFN-alpha, as compared with lethal ip infection.

Animals↗

PubMed1990

Antibodies of different human IgG subclasses show distinct patterns of affinity maturation after immunization with keyhole limpet haemocyanin.

The functional affinities of antibodies of different IgG subclasses were measured in normal individuals during the primary, secondary and tertiary immune responses to keyhole limpet haemocyanin (KLH). IgG1 responses showed marked affinity maturation between Days 7 and 21 after primary and by Day 7 after secondary and subsequent immunizations, correlating with an expansion of high-affinity antibody populations. When present, IgG2 responses were of low titre but high functional affinity with no change in response to immunization and may represent a T-independent cross-reacting response with a carbohydrate epitope of KLH. IgG3 responses were variable but generally of low titre and low functional affinity, although those of higher titre and affinity were associated with secondary delayed-type hypersensitivity (DTH) and clinical reactions to KLH. In contrast to IgG1, IgG4 antibodies were not detected until 1 year after primary immunization, when they were found at low titre but high functional affinity. Following secondary immunization, IgG4 titres increased rapidly but without any further increase in affinity. The emergence of high-affinity IgG4 antibodies coincided with a loss of the high-affinity IgG1 populations, suggesting a preferential switch with time from high-affinity IgG1 antibodies to IgG4.

Adult↗

PubMed2003

Longitudinal study of humoral immune responses in HIV type 1 subtype CRF01_AE (E)-infected Thai patients with different rates of disease progression.

Identification of immune correlates associated with disease progression will provide information for HIV-1 vaccine design in countries such as Thailand, where the prevalent subtypes (B and CRF01_AE [E]) are characterized. In this study, plasma viral load and humoral immune responses were measured in 20 HIV-1 subtype E-infected Thai patients with different rates of disease progression, based on CD4(+) T cell decline and clinical symptoms. Nine progressors (PRs) and 11 slower progressors (SPs) were evaluated. CD4(+) T cell counts were inversely correlated with viral load (p = 0.004) and positively correlated with p24 Ab (p = 0.022). In progressors, p24 Ab showed a significant decrease (p < 0.001) over time. V3 and gp41 Ab did not change significantly in either group. Both CD4-binding site (CD4/gp120BS) and gp120 titers correlated positively with neutralizing antibody (NAb) against both a subtype E cell line-adapted virus (NP03) and a primary isolate (TH023). However, V3 Ab correlated only with NAb against NP03 (p < 0.001). Increased NAb over time was observed more frequently in SPs as compared with PRs, against both the TH023 (p = 0.004) and NPO3 (p = 0.004) viruses. Cross-clade antibody-dependent cellular cytotoxicity was demonstrated in both groups. These data suggest that in HIV-1 subtype E infection, declining p24 Ab titer is a predictive marker of disease progression, as described for subtype B. Furthermore, in subtype E-infected patients, slower progressors retain the immune competence to develop new antibody responses to Env over time; these evolving responses may contribute to prolonged survival during HIV-1 disease progression.

Antibody-Dependent Cell Cytotoxicity↗

PubMed2001

Nasal or intramuscular immunization of mice with influenza subunit antigen and the B subunit of Escherichia coli heat-labile toxin induces IgA- or IgG-mediated protective mucosal immunity.

Local mucosal IgA antibodies play a central role in protection of the respiratory tract against influenza virus infection. Therefore, new-generation influenza vaccines should aim at stimulating not only systemic, but also local antibody responses. Previously, we demonstrated that the recombinant B subunit of the Escherichia coli heat-labile toxin (LTB) is a potent adjuvant towards nasally administered influenza subunit antigen. Here, we investigated the protection conferred by LTB-supplemented influenza subunit antigen given intranasally (i.n.) or intramuscularly (i.m.) to mice. Both i.n. and i.m. immunization with subunit antigen and LTB completely protected the animals against viral infection. Protection upon i.n. immunization was associated with the induction of antigen-specific serum IgG and mucosal IgA, whereas protection upon i.m. immunization correlated with strong serum and mucosal IgG, but not IgA responses. We conclude that LTB-supplemented influenza subunit antigen, given either i.n. or i.m, induces protective antibody-mediated mucosal immunity and thus represents a promising novel flu vaccine candidate.

Adjuvants, Immunologic↗