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PubMed1996

Immune response in mice following immunization with DNA encoding fragment C of tetanus toxin.

Tetanus toxin is a potent neurotoxin synthesized by Clostridium tetani. Immunization with fragment C protein, the nontoxic C-terminal domain of tetanus toxin, will protect mice against lethal challenge with tetanus toxin. A synthetic gene encoding fragment C (tetC) had previously been shown to express high levels of fragment C in Saccharomyces cerevisiae. A plasmid, pcDNA3/tetC, which encodes the synthetic tetC gene expressed under the control of the human cytomegalovirus major intermediate-early promoter/enhancer region, was constructed. Expression of fragment C was observed in eukaryotic cells growing in vitro following transfection with pcDNA3/tetC. The immune response induced by intramuscular immunization with pure pcDNA3/tetC DNA was evaluated in a murine model. Anti-fragment C serum immunoglobulin and proliferative responses in splenocytes were observed in BALB/c mice following two immunizations with pcDNA3/tetC. The major immunoglobulin G subclass that recognized fragment C was immunoglobulin G2a, and the stimulated splenocytes secreted high levels of gamma interferon. Immunity to tetanus is dependent on the presence of neutralizing serum antibodies against tetanus toxin. Sufficient anti-fragment C serum immunoglobulins were induced by DNA-mediated immunization to protect mice against lethal challenge with tetanus toxin.

Animals↗
PubMed2000

Interleukin 12 as an adjuvant to WI-1 adhesin immunization augments delayed-type hypersensitivity, shifts the subclass distribution of immunoglobulin G antibodies, and enhances protective immunity to Blastomyces dermatitidis infection.

Cell-mediated immunity is pivotal in host resistance to Blastomyces dermatitidis infection. Immunization of mice with the WI-1 adhesin enhances resistance against experimental pulmonary infection but elicits features of a mixed T-helper-cell immune response. Immune mice acquire delayed-type hypersensitivity (DTH) but also high titers of WI-1-specific immunoglobulin G1 (IgG1) and IgG2b, a result indicative of T-helper-2 cellular immunity. We report that interleukin-12, used as an adjuvant for WI-1 immunization, augments DTH, shifts the balance of the T-helper phenotype toward Th1, and enhances resistance to B. dermatitidis infection.

Adhesins, Bacterial↗
PubMed2002

Specific immune responses and enhancement of murine pulmonary clearance of Moraxella catarrhalis by intranasal immunization with a detoxified lipooligosaccharide conjugate vaccine.

Moraxella catarrhalis is an important human mucosal pathogen. This study investigated the effect of intranasal immunization with a detoxified-lipooligosaccharide-cross-reactive mutant of diphtheria toxin (dLOS-CRM) vaccine candidate on pulmonary clearance following an aerosol challenge of mice with M. catarrhalis. Intranasal immunization with dLOS-CRM plus cholera toxin induced a significantly dose-dependent increase of immunoglobulin A (IgA) and IgG in the nasal wash, lung lavage fluid, saliva, and fecal extract. In addition, serum IgG, IgM, and IgA against LOS of M. catarrhalis were detected. LOS-specific antibody-forming cells were found in the nasal passages, spleens, nasally associated lymphoid tissues, cervical lymph nodes, lungs, and Peyer's patches using an enzyme-linked immunospot assay. The dLOS-CRM vaccine induced a significant bacterial clearance (70 to 90%) of both homologous and heterologous strains in the lungs compared to that observed in the controls (P < 0.01). Intriguingly, intranasal immunization with dLOS-CRM showed a higher level of bacterial clearance compared with subcutaneous injections with dLOS-CRM. These data indicate that dLOS-CRM induces specific mucosal and systemic immunity through intranasal immunization and also provides effective bacterial clearance. On the basis of these results, we believe that dLOS-CRM should undergo continued testing to determine whether it would induce protective immune response in humans.

Administration, Intranasal↗
PubMed2003

Protective efficacy of anti-Helicobacter pylori immunity following systemic immunization of neonatal mice.

Helicobacter pylori infection of the gastric mucosa is a significant cause of morbidity and mortality because of its etiologic role in symptomatic gastritis, peptic ulcer disease, and gastric adenocarcinoma. Infection occurs in young children; therefore, a prophylactic vaccine would have to be administered within the first year of life, a period thought to be immunologically privileged. We investigated vaccine formulations administered by different routes to confer protective anti-H. pylori immunity in neonatal mice. Neonatal mice immunized with a single dose of vaccine in complete Freund's adjuvant (CFA) generated antigen-specific gamma interferon-, interleukin-2 (IL-2)-, IL-4-, and IL-5-secreting T cells in numbers similar to those in immunized adult mice, while vaccine administered to neonates in incomplete Freund's adjuvant (IFA) induced such cells in reduced numbers compared to those in adult mice. Both IFA and CFA, however, provided partial protection from a challenge with infectious H. pylori when the vaccine was administered subcutaneously. Neonatal immunized mice also had reduced bacterial loads when immunized intraperitoneally with CFA. In all cases, protection was equivalent to that achieved when adult counterparts were immunized. These studies suggest that an efficacious vaccine might be successfully administered to very young children to prevent perinatal infection of H. pylori.

Aluminum Hydroxide↗
PubMed1973

Immunization of mice with live attenuated encephalomyocarditis virus: local immunity and survival.

Mice were vaccinated with an attenuated encephalomyocarditis (EMC) virus strain by the intraperitoneal (i.p.) route and by various ways of respiratory administration: aerosol exposure and intratracheal (i.t.) and intranasal (i.n.) instillation. A linear relationship was found between vaccine dose and the resulting serum antibody titer. The effectiveness of the vaccine was determined by measuring the 50% protective doses (ED(50) values) after a lethal challenge with live virulent virus given by the i.p. route. For all three methods of respiratory immunization essentially the same ED(50) value was found, about 200 plaqueforming units (PFU), but i.p. immunization was less effective, the ED(50) value being about 600 PFU. To investigate the protective effect of local immunity, mice were vaccinated i.p. or i.n. and challenged by the i.n. route. The same ED(50) values were found as after i.p. challenge, indicating that the degree of protection afforded by the vaccine depends only on the route of vaccination and not on the route of challenge. This means that protection depends largely on systemic immunity and that local immunity plays only a minor role in this system. The results are discussed in relation to the feasibility of respiratory immunization against animal viruses.

Administration, Intranasal↗
PubMed1967

Experimental salmonellosis. 8. Postinfective immunity and its significance for conferring cellular immunity.

In the process of live-vaccine immunization of Salmonella enteritidis infection in mice, the relation between the number of bacteria in the organs of mice and their protecting effect was studied. Treatment with antibiotics was used to control the number of immunizing bacteria in the tissues. Mice, which were infected with 10(-5) mg (1,000 mouse MLD) of virulent S. enteritidis and treated with kanamycin simultaneously, acquired high antilethal resistance against infection with the same organisms. However, the administration of large amounts of kanamycin, which caused a rapid decrease in bacterial numbers in the organs of infected mice, was incapable of conferring immunity. This indicated the necessity of persistence of live bacteria in the host for the production of immunity. A large number of microorganisms were maintained for 53 weeks in a diffusion chamber inserted into the mouse abdominal cavity. The mice implanted with diffusion chambers containing large numbers of virulent S. enteritidis did not acquire antilethal resistance against infection with the same organisms, although agglutinins against S. enteritidis were observed in these mice. Agglutinin was also found in the fluid contained in diffusion chambers inserted into mice immunized with a killed vaccine of S. enteritidis. This indicated that antibody penetrated the membrane filter of diffusion chambers from outside to inside and vice versa. From these results, it is suggested that contact of live microorganisms with the host cell is necessary for conferring postinfective immunity in salmonellosis.

Agglutination Tests↗
PubMed2004

Immunization with hepatitis C virus-like particles induces humoral and cellular immune responses in nonhuman primates.

We have previously reported the production of hepatitis C virus-like particles (HCV-LP) using a recombinant baculovirus containing the cDNA of the HCV structural proteins (core, E1, and E2). These particles resemble the putative HCV virions and are capable of inducing strong and broad humoral and cellular immune responses in mice. Here we present evidence on the immunogenicity of HCV-LP and the effects of novel adjuvant systems in a nonhuman primate model, the baboon. Three groups of four baboons were immunized with HCV-LP, HCV-LP and adjuvant AS01B (monophosphoryl lipid A and QS21), or HCV-LP and the combination of AS01B and CpG oligodeoxynucleotides 10105. After four immunizations over an 8-month period, all animals developed HCV-specific humoral and cellular immune responses including antibodies to HCV structural proteins and gamma interferon(+) (IFN-gamma(+))CD4(+) and IFN-gamma(+)CD8(+) T-cell responses. The immunogenicity of HCV-LP was only marginally enhanced by the use of adjuvants. The overall HCV-specific immune responses were broad and long lasting. Our results suggest that HCV-LP is a potent immunogen to induce HCV-specific humoral and cellular immune responses in primates and may be a promising approach to develop novel preventive and therapeutic modalities.

Adjuvants, Immunologic↗
PubMed2005

The immune response to human metapneumovirus is associated with aberrant immunity and impaired virus clearance in BALB/c mice.

Human metapneumovirus (HMPV), recently identified in isolates from children hospitalized with acute respiratory tract illness, is associated with clinical diagnosis of pneumonia, asthma exacerbation, and acute bronchiolitis in young children. HMPV has been shown to cocirculate with respiratory syncytial virus (RSV) and mediate clinical disease features similarly to RSV. Little is known regarding the pathophysiology or immune response associated with HMPV infection; thus, animal models are needed to better understand the mechanisms of immunity and disease pathogenesis associated with infection. In this study, we examine features of the innate and adaptive immune response to HMPV infection in a BALB/c mouse model. Primary HMPV infection elicits weak innate and aberrant adaptive immune responses characterized by induction of a Th2-type cytokine response at later stages of infection that coincides with increased interleukin-10 expression and persistent virus replication in the lung. Examination of the cytotoxic T lymphocyte and antibody response to HMPV infection revealed a delayed response, but passive transfer of HMPV-specific antibodies provided considerable protection. These features are consistent with virus persistence and indicate that the immune response to HMPV is unique compared to the immune response to RSV.

Animals↗
PubMed1976

Immunity in syphilis. Studies in active immunity.

Support for the concept of the development of immunity during the course of syphilis is avaiable in the literature. In experimental syphilis in rabbits, some immunity is present approximately 3 weeks after infection with Treponema pallidum. Resistance to re-infection increases to a maximum at approximately 3 months after infection. Termination of this state by penicillin treatment within this 3-month period may enable re-infection to be accomplished. Attempts to reproduce this state of immunity experimentally by injection of T. pallidum itself, or protein derivatives, or ultrasonic disintegrates obtained from T. pallidum or non-pathogenic treponemes, have been unsuccessful. However, promising results in rabbits have resulted from injecting T. pallidum suspensions attenuated by storage at 4 degrees C, penicillin, or gamma irradiation, and also by suspensions preserved by glutaraldehyde. In the present study, partial resistance to intratesticular challenge in rabbits with T. pallidum has been obtained by immunization with a variety of non-pathogenic treponemes, as exemplified by the strains Nichols, Kazan 2, 4, 5, and 8, Treponema minutum, Treponema ambigua, Treponema refringens and Treponema microdentium. Success is attributed to the processing of immunizing antigens at 4 degrees C and storage until use at -20 degrees C. Attempts to attenuate T. pallidum by immunological means, namely, passage through a limited number of immunized rabbits, were unsuccessful.

Animals↗
PubMed1987

Lack of immune deficiency in sarcoidosis: compartmentalisation of the immune response.

The original findings of peripheral anergy in sarcoidosis led to the conclusion that sarcoidosis was a disease associated with immune deficiency, but patients with sarcoidosis do not appear to suffer from repeated infections suggestive of immune suppression. With the technique of bronchoalveolar lavage it is now possible to examine the local immune response within the lung, the most commonly affected organ in sarcoidosis. In this study three different indices of cell mediated immunity (lymphocyte transformation, interleukin-2 production, and interleukin-1 production) have been examined by comparison of cells recovered by lavage with those collected from peripheral blood. It was found that in vitro anergy was confined to peripheral blood cells, where all three markers of the immune response used in this study was impaired in the 12 patients with sarcoidosis group when compared with results in the 12 controls, with the most depressed responses seen in those patients classified as having active disease (lymphocyte proliferation 45% (SD 17%); interleukin-2 production 44% (13%), and interleukin-1 production 31% (10%) of control levels). By contrast, T lymphocytes recovered from the lungs of patients with sarcoidosis showed a greater response than did those from controls in terms of lymphocyte transformation and interleukin-2 production; these differences were greatest in those with active disease (lymphocyte proliferation 209% (27%) and interleukin-2 production 202% (19%) of control levels). Interleukin-1 production by cells of the monocyte lineage recovered from the lung gave similar results to those of the control and sarcoid groups. It is concluded that the anergy seen in the peripheral blood compartment possibly reflects redistribution of T lymphocytes rather than a generalised immune deficiency.

Adult↗
PubMed1999

Isoforms of the major allergen of birch pollen induce different immune responses after genetic immunization.

BACKGROUND: Recent publications indicate that immunization with plasmid DNA encoding allergens might represent a potential approach in allergen-specific immunotherapy. OBJECTIVE: In the present study we have compared the immune responses induced by plasmid DNA encoding for two isoforms of Bet v 1, the major allergen of birch pollen. METHODS: BALB/c mice were injected intradermally with plasmid DNA encoding for the genes of Bet v 1a (pCMV-Beta) and Bet v 1d (pCMV-Betd). In addition, the effect of immunostimulatory DNA sequences was investigated by appending and/or coinjecting CpG motifs. Antibody responses and IFN-gamma and IL-4 levels were measured by ELISA. Allergen-specific proliferation was determined by incorporation of [(3)H]-thymidine. RESULTS: The two isoforms induced a similar humoral response. The lack of any IgE production and the ratio of IgG1 to IgG2a clearly indicated a Th-1-type response. The antisera against both isoforms were highly cross-reactive, which was supported by the energy plot indicating similar folding of the two protein isoforms. However, determination of IFN-gamma and IL-4 in the serum elicited a strikingly different cytokine profile during the course of the immune response. In contrast to pCMV-Beta, pCMV-Betd caused no significant allergen-specific proliferation and induced only marginal levels of the key cytokines. CONCLUSIONS: Based on the assumption that the induction of a strong Th-1 type response is a prerequisite for successful treatment of allergy, our results favor the use of isoform Bet v 1a in combination with CpG motifs for a novel type of allergen immunotherapy based on plasmid DNA immunization. Additionally, the data also confirm the assumption that the antigen itself can have a marked influence on the immune response after genetic immunization.

Allergens↗
PubMed1994

Changes in cellular immune function after immune specific guided imagery and relaxation in high and low hypnotizable healthy subjects.

This article presents the results of two investigations, each measuring cellular immune function on 3 investigation days 1 week apart in 15 high and 15 low hypnotizable healthy subjects randomly selected for three groups: (1) a guided imagery group receiving instructions to enhance cellular immune function: (2) a relaxation group which did not receive instructions regarding the immune system, and (3) a control group. Study 1 investigated changes in monocyte chemotaxis (MC) and lymphocyte proliferative response (LPR) to three mitogens, while natural killer cell activity (NKCA) was measured in study 2. The results show similar patterns of brief decreases in LPR and NKCA immediately after intervention on all investigation days in both the imagery and relaxation groups. Increases in MC were found in both intervention groups on day 1. On a follow-up investigation day in study 2, a brief stress task yielded a slight increase in NKCA. In study 2, the control group showed decreases in NKCA similar to those observed in the two intervention groups. In general there were no significant changes in preintervention immune function throughout the investigation period. When comparing the effects in high and low hypnotizable subjects, we found that high hypnotizables showed greater decreases in LPR and NKCA than low hypnotizables. There are several inconsistencies between the results of the limited number of investigations studying the effects of guided imagery and relaxation on immune function. These differences may in part be explained by differences in methodology, time intervals between blood sampling, and subject characteristics such as age, health status and hypnotizability. The inconsistent results make it premature to make inferences about possible benefits of the application of these techniques in the treatment of immune related diseases, and further investigations are needed.

Adolescent↗
PubMed1980

Immune responses after localized lung immunization in the dog.

The immune response in immunized and unimmunized bronchoalveolar spaces, as well as in the blood, was measured after localized deposition of antigen in the lung. Using a fiberoptic bronchoscope, groups of dogs were immunized with sheep red blood cells (SRBC) deposited into a single airway of the left apical or right apical lung lobes. Bronchoalveolar cells were obtained by lung lavage through the fiberoptic bronchoscope from the immunized lung lobe, as well as from lung lobes that did not receive antigen. Lavage cells and blood samples were collected at 3 to 21 days after immunization. The total number of lymphocytes, macrophages, and polymorphonuclear leukocytes, and the number of lymphoid cells producing anti-SRBC IgM and IgG antibodies were determined. Our results indicated that the highest number of antibody-forming cells (AFC) were found in the immunized lung lobes. An elevated, but significantly lower number of AFC were observed in the unimmunized lung lobes. The number of IgM and IgG AFC in the blood reached peak concentrations 3 to 7 days earlier than the AFC in the lung. We concluded from our data that the blood is an important source of the AFC found in the lung.

Animals↗
PubMed1985

Formation of soluble immune complexes by complement in sera of patients with various hypocomplementemic states. Difference between inhibition of immune precipitation and solubilization.

To examine whether the ability of complement to form soluble immune complexes plays a role in preventing immune complex-mediated diseases, we analyzed the capacity of complement to inhibit immune precipitation (IIP) and to solubilize preformed immune aggregates (SOL) in 23 sera of patients with various hypocomplementemic states, and we correlated the results of these studies with the clinical syndromes found in the various patients. In sera with deficiency or depletion of early classical pathway components, IIP was profoundly altered, whereas SOL was delayed but in the normal range. In contrast, in sera with C3 depletion but intact classical pathway and in properdin-deficient serum, IIP was initially preserved, whereas SOL was abolished. Since the incidence of immune complex diseases in various hypocomplementemic states correlates with the severity of IIP defects, but not with reduced SOL, it is suggested that IIP is an essential biological function of complement that prevents the rapid formation of insoluble immune complexes in vivo.

Antigen-Antibody Complex↗
PubMedDate not supplied

Use of public school immunization data to determine community-level immunization coverage.

OBJECTIVES: To evaluate whether immunization data collected on a child's entry into kindergarten, i.e., Chicago Public School Immunization Data (PSID), was comparable to coverage levels determined by the National Immunization Survey (NIS) and to use these data to identify community areas with consistently low immunization coverage. METHODS: The Chicago Department of Public Health obtained four years of PSID (2000-2003); these data included demographic information, home address, and immunization records. Coverage levels were determined in two ways: (1) one dose of measles-containing vaccine (MCV) and (2) four doses of diphtheria and tetanus toxoids and pertussis vaccine, three doses of poliovirus vaccine, and one dose of measles-containing vaccine (the 4:3:1 series), stratified by racial/ethnic group; these levels were compared to NIS estimates for the respective time periods. We used geographic information system software to illustrate variations in coverage levels between distinct community areas within Chicago. RESULTS: Year 2000 MCV coverage levels determined from PSID closely approximated NIS estimates (84.6% vs. 87.2% +/- 4.6%, respectively). MCV coverage levels determined by race/ethnicity from PSID were within the 95% confidence intervals (CI) for all racial categories (white, 89.5% vs. 92.2% +/- 6.4%; black, 79.0% vs. 83.5% +/- 9.4%; Hispanic, 89.5% vs. 87.5% +/- 5.8%). Comparison of PSID and NIS 4:3:1 coverage levels revealed similar findings. For each study year, PSID identified 12 community areas with consistently low MCV coverage levels, i.e., < 80%. CONCLUSIONS: PSID closely approximated NIS coverage estimates for MCV and 4:3:1 immunization. These methods can be used by state and city health departments to identify and direct resources to communities at greatest need.

Black or African American↗
PubMed2004

Sex differences in immune responses and immune reactivity to stress in adolescents.

The immune system is the body's major defense mechanism against disease. However, psychosocial factors, such as stress, can modulate various immune responses. Although they have been examined in adult humans and other animals, sex differences in immune responses and immune reactivity to stress have rarely been examined in adolescents, particularly comparing healthy and asthmatic adolescents. In 151 healthy and asthmatic high school adolescents (91 females and 60 males), natural killer cell (NK) cytotoxicity, polymorphonuclear leukocyte (PMN) superoxide release, lymphocyte proliferative responses, and CD subsets were measured twice: once during mid-semester and again during final examinations. There was little difference in these measures between healthy and asthmatic adolescents. Similarly, only sex difference was noted in NK cytotoxicity at a 25:1 effector-to-target cell ratio, with males showing significantly higher responses than females. For PMN superoxide release, females significantly increased their responses during final examinations, whereas males demonstrated no changes. For lymphocyte proliferative responses, both females and males increased their responses during final examinations, but the magnitude of increase was much greater in males. Furthermore, racial comparisons indicated that African American adolescents (n = 16), as compared with Caucasian adolescents (n = 128), had significantly higher responses in PMN superoxide release to N-Formyl-Met-Leu-Phe (FMLP) activation during mid-semester and lymphocyte proliferative responses at both time points. Nevertheless, the overall findings indicate limited differences in immune responses and immune reactivity to stress in adolescents between males and females, healthy and asthmatic adolescents, and Caucasians and African Americans. However, further investigations with larger samples are warranted.

Adolescent↗
PubMed2006

Protective and destructive immunity in the periodontium: Part 1--innate and humoral immunity and the periodontium.

Based on the results of recent research in the field, the present paper will discuss the protective and destructive aspects of the innate vs. adaptive (humoral and cell-mediated) immunity associated with the bacterial virulent factors or antigenic determinants during periodontal pathogenesis. Attention will be focused on: (i) the Toll-like receptors (TLR), the innate immune repertoire for recognizing the unique molecular patterns of microbial components that trigger innate and adaptive immunity for effective host defenses, in some general non-oral vs. periodontal microbial infections; (ii) T-cell-mediated immunity, Th-cytokines, and osteoclastogenesis in periodontal disease progression; and (iii) some molecular techniques developed and used to identify critical microbial virulence factors or antigens associated with host immunity (using Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis as the model species). Therefore, further understanding of the molecular interactions and mechanisms associated with the host's innate and adaptive immune responses will facilitate the development of new and innovative therapeutics for future periodontal treatments.

Adaptor Proteins, Signal Transducing↗
PubMed1993

Why aren't preschoolers immunized? A comparison of parents' and providers' perceptions of the barriers to immunizations.

A community-wide survey of 302 parents of 2-year-old children and 90 private medical practitioners in a large midwestern city revealed low immunization rates (31%) and differences in parent and provider perceptions of barriers to preschool immunizations. Parents most frequently identified barriers of system factors such as cost, lack of insurance coverage, and long office waits. System barriers were reported across differing sources of immunizations (private physician as well as public clinics) and were pervasive across income groups. Providers were more likely to report barriers of parental difficulties with forgetting immunizations or not knowing when the immunizations were due. Even though providers identified parental shortcomings with scheduling as problematic, only one fifth employed tracking and reminder systems. Implications of findings for modifications of the delivery of immunization services and for parent education are discussed.

Adult↗