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Immunization of mice against encephalomyocarditis virus. II. Intraperitoneal and respiratory immunization with ultraviolet-inactivated vaccine: effect of Bordetella pertussis extract on the immune response.

Mice were immunized by intraperitoneal (ip) or respiratory administration of ultraviolet-inactivated virus alone or with Bordetella pertussis extract (BPE) as an adjuvant. The effect of immunization was tested by determination of antibody titers and by survival of a lethal challenge with 200 LD(50) of a virulent (large-plaque variant) strain of EMC virus. For plain vaccine the ip 50% effective dose (ED(50)) was 37 hemagglutination units (HAU; ca. 4 x 10(6) plaque-forming unit equivalents); with adjuvant the ip ED(50) was reduced to 20 HAU. After respiratory immunization by intratracheal injection, an ED(50) value of 100 HAU was found, which was not affected by BPE. After ip vaccination the primary immune response was enhanced by BPE, but the challenge response, measured 3 weeks after challenge, was unaffected. Respiratory immunization induced a primary response which was not influenced by BPE, but here the challenge response was enhanced by the adjuvant. After secondary treatment (challenge or booster vaccination) serum antibodies and protection against challenge persisted for at least 1 year.

Adjuvants, Immunologic↗

Mefloquine for preventing malaria in non-immune adult travellers.

OBJECTIVES: Mefloquine has now largely replaced earlier malaria prophylaxis drugs which are no longer considered to be effective against all Plasmodium species, due to parasite resistance. However mefloquine may be associated with neuropsychological harmful effects. The objective of this review was to assess the effects of mefloquine in adult travellers. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group trials register, Medline, Embase, Lilacs, Science Citation Index and reference lists of articles. We contacted researchers in the subject of malaria chemoprophylaxis, and drug companies. SELECTION CRITERIA: Randomised trials comparing mefloquine with other standard prophylaxis or placebo in non-immune adult travellers. DATA COLLECTION AND ANALYSIS: The two reviewers independently assessed trial quality and extracted data. Study authors were also contacted. MAIN RESULTS: Ten trials involving 2750 non-immune adult travellers were included. One trial comparing mefloquine with placebo showed mefloquine prevented malaria episodes in an area of drug resistance (odds ratio 0.04, 95% confidence interval 0.02 to 0.08). Withdrawals in the mefloquine group were consistently higher in four placebo controlled trials (odds ratio 3. 56, 95% confidence interval 1.67 to 7.60). In five trials comparing mefloquine with other chemoprophylaxis, no difference in tolerability was detected. REVIEWER'S CONCLUSIONS: Mefloquine prevents malaria, but there is not enough evidence to evaluate its tolerability and toxicity, particularly for general travellers.

Adult↗

Effect of immunization on reproducvive performance, embryo quality and progesterone in Rasa Aragonesa ewes actively immunized against androstenedione or passively immunized against testosterone.

A total of 217 Rasa Aragonesa ewes were used to test two immunization treatments: 1.Active immunization against androstenedione: ewes immunized in previous matings (androstenedione, reimmunized; AR groups, n=58) or not (first immunization; AF groups n=64) were boosted either 2 or 4 wk before mating. 2.Passive immunization against testosterone: antisera were injected either at sponge withdrawal (zero time; T0 group, n=21) or 1 wk previously (Tl group, n=22). We used 52 ewes as controls (C group). Half of each group was used either to record reproductive performance or to embryo viability assessment. Prolificacy was significantly increased in ewes which reached a moderate antibody level, independently of the treatment. Fertility was lower in AR ewes that attained a high antibody titre (P<0.01). The percentage of viable embryos recovered was lower in AF ewes (P<0.01), and in ewes whose testosterone antibody titre was high (P<0.05), compared to C group. It was proven that similar or lower antibody levels were more harmful for ewes from AF and Tl than for ewes from AR or T0 groups. The proportion of nonfertilized recovered ova was not significant. Progesterone levels were notably increased in AR ewes (P<0.001) independently of ovulation rate and were positively correlated to antibody titre at mating (P<0.01) but these events were not observed in T ewes. These findings indicate that after androgen immunoneutralization, only those ewes having antibody titres within a limited range at mating had improved reproductive performance. Further research is needed in order to understand the role that progesterone plays in immunized ewes.

Journal Article↗

A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP) Part II: immunization of adults.

Hepatitis B vaccination is the most effective measure to prevent hepatitis B virus (HBV) infection and its consequences, including cirrhosis of the liver, liver cancer, liver failure, and death. In adults, ongoing HBV transmission occurs primarily among unvaccinated persons with behavioral risks for HBV transmission (e.g., heterosexuals with multiple sex partners, injection-drug users [IDUs], and men who have sex with men [MSM]) and among household contacts and sex partners of persons with chronic HBV infection. This report, the second of a two-part statement from the Advisory Committee on Immunization Practices (ACIP), provides updated recommendations to increase hepatitis B vaccination of adults at risk for HBV infection. The first part of the ACIP statement, which provided recommendations for immunization of infants, children, and adolescents, was published previously (CDC. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices [ACIP]. Part 1: immunization of infants, children, and adolescents. MMWR 2005;54[No. RR-16]:1-33). In settings in which a high proportion of adults have risks for HBV infection (e.g., sexually transmitted disease/human immunodeficiency virus testing and treatment facilities, drug-abuse treatment and prevention settings, health-care settings targeting services to IDUs, health-care settings targeting services to MSM, and correctional facilities), ACIP recommends universal hepatitis B vaccination for all unvaccinated adults. In other primary care and specialty medical settings in which adults at risk for HBV infection receive care, health-care providers should inform all patients about the health benefits of vaccination, including risks for HBV infection and persons for whom vaccination is recommended, and vaccinate adults who report risks for HBV infection and any adults requesting protection from HBV infection. To promote vaccination in all settings, health-care providers should implement standing orders to identify adults recommended for hepatitis B vaccination and administer vaccination as part of routine clinical services, not require acknowledgment of an HBV infection risk factor for adults to receive vaccine, and use available reimbursement mechanisms to remove financial barriers to hepatitis B vaccination.

Adult↗

Immune-stimulating complexes as adjuvants for inducing local and systemic immunity after oral immunization with protein antigens.

Orally active synthetic vaccines containing purified antigens would have many benefits for immunizing against systemic and mucosal diseases. However, several factors have limited the development of such vaccines, including the poor immunogenicity of purified proteins and their usual ability to induce tolerance when given orally. Here, we show that incorporation of ovalbumin (OVA) into immune-stimulating complexes (ISCOMS) containing saponin prevents the induction of oral tolerance in mice. In parallel, the spleen and mesenteric lymph node of mice fed OVA ISCOMS are primed for class I major histocompatibility complex (MHC)-restricted cytotoxic T-cell activity which recognizes physiologically processed epitopes on OVA. Oral immunization with OVA ISCOMS also stimulates high secretory IgA antibody responses in the intestine itself, as well as serum IgG antibodies. None of these active immune responses are detectable in mice fed OVA alone. Despite the potent priming of mucosal priming by OVA ISCOMS, re-exposure to antigen does not induce the intestinal immunopathology found in other systems after the breakdown of oral tolerance. Thus, ISCOMS have several unique properties as vectors for oral immunization and could provide a basis for future mucosal vaccines.

Adjuvants, Immunologic↗

Cellular and humoral immune responses to measles in immune adults re-immunized with measles vaccine.

The objective of this study was to characterize the kinetics of the cellular and humoral immune responses elicited by measles vaccine given to previously immune adults. The cellular and humoral immune responses to measles were measured in seven healthy adults, before vaccination and at 1, 2, 3, and 4 weeks and 3 months after vaccination, using measles-specific T-cell proliferation and plaque reduction neutralization assays. All study subjects had detectable measles antibodies, but only six (85%) showed protective titers, defined as >1:120, before immunization. However measles-specific T-cell proliferation was not detectable before vaccination in any of the subjects. The six subjects with protective titers showed a positive stimulation index (SI) of >3.0 within the first 4 weeks after vaccination, an SI of 5 at the 4th week, and an SI of 3 at 3 months after vaccination. The subject with a low antibody titer (1:99) before vaccination developed a high SI at 3 months after vaccination. This subject was the only participant whose neutralizing antibody titers increased more than 4-fold by 3 months after vaccination. No significant increases in geometric mean titers were detected in the other six subjects during the follow-up period. These data suggest that high measles antibody titers interfere with the humoral response in subjects who receive a booster immunization, whereas the cellular response is boosted at least transiently, after revaccination.

Adult↗

Single dose of anti-D immune globulin at 75 microg/kg is as effective as intravenous immune globulin at rapidly raising the platelet count in newly diagnosed immune thrombocytopenic purpura in children.

OBJECTIVE: To conduct a randomized prospective trial of immune globulin treatment for 105 Rh+ children with newly-diagnosed immune thrombocytopenic purpura and a platelet count<20,000/microL, to determine whether anti-D immune globulin (anti-D) is as effective as intravenous immune globulin (IVIg). STUDY DESIGN: Eligible patients received either a single intravenous dose of 50 microg/kg anti-D (anti-D50), 75 microg/kg anti-D, (anti-D75), or 0.8 g/kg IVIg, (IVIg). Patients were monitored for response to treatment and adverse events. RESULTS: By 24 hours after treatment 50%, 72%, and 77% of patients in the anti-D50, anti-D75, and IVIg groups, respectively, had achieved a platelet count>20,000/microL (P=.03). By day 7, hemoglobin concentrations decreased by 1.6 g/dL, 2 g/dL, and 0.3 g/dL in the anti-D50, anti-D75, and IVIg groups, respectively. Headache, fever, or chills occurred least often in the anti-D50 group. CONCLUSIONS: A single 75 microg/kg dose of Anti-D raised the platelet count in children with newly diagnosed immune thrombocytopenic purpura more rapidly than standard-dose anti-D and as effectively as IVIg, with an acceptable safety profile.

Adolescent↗

Adoptive transfer of immunity to dysentery bacilli with immune T lymphocytes from mice orally immunized with Shigella sonnei bacilli.

It has been found previously that live virulent dysentery bacilli administered orally into mice induced immunity against subsequent infection of the animals with lethal dose of these organisms introduced i.v. The experiments revealed that this immunity could be transferred with spleen cells. This report shows that treatment with antiserum prepared against the mouse theta antigen, in the presence of complement, abrogated the ability of specific immune cells to protect the recipient mice against lethal infection with dysentery bacilli. However, treatment of the cells with anti-immunoglobulin serum, in the presence of complement, did not affect the capacity of the immune cells in the adoptive transfer experiments to protect the recipients against dysentery bacilli. Thus, T cells are required for the development of the cell mediated response occurring after oral immunization of mice with live pathogenic bacilli.

Administration, Oral↗

Comparison of the humoral and cellular immune response after immunization with live, UV inactivated herpes simplex virus and a subunit vaccine and efficacy of these immunizations.

Antibody and cell-mediated immune responses were measured in rabbits immunized with live, UV inactivated herpes simplex virus or with a subunit vaccine containing envelope proteins. All the types of immunization procedures induced the production of antibody as well as a specific cellular immunity. Furthermore, the subunit vaccine was as effective as the immunization with live or UV inactivated virus to prevent death upon challenge with live HSV. Live HSV induced a transient unresponsiveness of both B and T cells to in vitro stimulation with various mitogens.

Animals↗

[Systemic humoral immune response to food antigens following oral immunization or immunization via the respiratory tract].

Differences and similarities of the systemic humoral immune response to cow's milk proteins were investigated after exposure of the gut or of the airways to antigen, both in children and in rabbits. Circulating antibodies were determined by radioimmunoassay (children and rabbits) and by enzyme-linked immunosorbent-assay in a small number of children. An age-dependent reference range was established, reflecting the rapid change of active antibody formation after oral immunization against bovine serum albumin in healthy, non-breastfed children up to the age of 24 months (n = 181). In contrast 16 children with recurrent aspiration due to anatomical disturbances or swallowing difficulties, all had antibody-titers well above this reference range. 7 of 9 children with cow's milk protein intolerance and with failure to thrive (oral immunization) also showed high concentrations of milk antibodies in the circulation. In adult rabbits immunized by oral or inhalational route, the vigorous immune response seen in recurrent aspiration could be mimicked. As investigated by enzyme-linked immunosorbent assay, higher titers of antibodies to bovine serum albumin, alpha-lactalbumin, beta-lactoglobulin, alpha-casein and bovine gammaglobulin could be shown in all isotypes tested (specific anti-IgG, -IgA, and -IgE) both in recurrent aspiration (n = 11) and cow's milk protein intolerance (n = 4) as compared to normal age-matched children (n = 14).

Animals↗

Cell preparation in immune response by immune ribonucleic acid. II. Independence of T lymphocytes in immune response against T-independent antigens.

The immune response of congenitally athymic (nude) mice induced by immune ribonucleic acid (iRNA) to lipopolysaccharides of Escherichia coli 0-55 (LPS) was studied. The thymus-independent nature of the immune response of mice to LPS was confirmed and nude mice responded to LPS in a manner similar to normal mice. An iRNA preparation extracted from the spleen of nude mice immunized with LPS could induce the proliferation of rosette-forming cells (RFC) in nude mice. iRNA preparations were insensitive to treatment with deoxyribonuclease and pronase, but were inactivated by ribonuclease treatment. The active fraction of the iRNA preparation had sedimentation values in a sucrose density gradient between 7 and 16 S and comprised only a small fraction of the total RNA present in the spleen cells, thereby indicating that the active moiety was one or more species of RNA. The anamnestic response was induced by treatment with iRNA made from the spleen of nude mice immunized with LPS. An increase in the number of rosette-forming cells (RFC), plaque forming cells (PFC) and formation of humoral antibody to LPS was seen after injection with a small amount of LPS 4 weeks after iRNA treatment.

Animals↗

Immune complexes, serum proteins, cell-mediated immunity, and immune regulation in patients with squamous cell carcinoma of the head and neck.

A collaborative study of the humoral and cellular immune status of patients with carcinoma of the Head and Neck (H&N) was conducted at the West Virginia University (WVU) hospital. In addition, blind-coded serum panels were supplied on H&N cancer patients being treated at the National Cancer Institute (NCI). Serum protein analysis of the WVU study groups revealed that at the pretreatment sampling, the alpha-1 acid glycoprotein (AGP), total complement, and IgA levels were significantly elevated. The AGP levels and total complement levels declined to normal levels in the post-treatment period, whereas the IgA levels remained elevated throughout the entire observation period. Levels of serum immune complexes (SIC) were measured in both the WVU and NCI H&N cancer populations using the polyethylene glycol (PEG) precipitation method. In both survey populations all cancer groups had significantly elevated levels of SIC when compared to any of the control populations. The SIC levels never returned to comparative normal values even in cases after successful treatment. A subpopulation of the WVU-H&N cancer study group underwent a short course of intravenous hyperalimentation prior to their treatment regimen. These patients demonstrated a transient decrease in their SIC levels as well as a concomitant increase in their in vitro cell-mediated immune (CMI) correlates. The analysis of in vitro CMI correlates of the WVU study group using both polyclonal mitogens and specific antigens demonstrated a significant depression in these parameters pretreatment and post-treatment. In addition, it was observed that the time course for elevation of selected serum proteins (i.e., IgA and SIC) correlated with concomitant drops in CMI activity. Investigations were also conducted into the effects of immune complex-rich serum fractions upon selected in vitro CMI correlates. Significant blockage of a normal donor leukocyte migration-inhibition assay was demonstrated. Also, a similar inhibition of the ability of normal human lymphocytes to form high affinity rosettes was accomplished with serum from H&N cancer patients.

Adult↗

The effect of measles-mumps-rubella (MMR) immunization on the immune responses of previously immunized primary school children.

Current policies for measles control call for administration of a second dose of vaccine to immunize those who failed to respond to the initial dose and to boost the responses of those with low levels of antibody. However, there has been concern expressed publicly that reimmunization may have adverse immunologic consequences. To determine the effects of reimmunization on immune responses, primary school children (N=38, mean age=6.14+/-0.35 years) with documented previous measles-mumps-rubella vaccine (MMR) immunization during infancy 4-5 years earlier were studied before and 1 month after receiving MMR as a part of routine reimmunization in Beer-Sheva, Israel. A substantial number of children were seronegative to measles (24%), mumps (34%) and rubella (44%). On reimmunization all seroconverted to mumps and rubella and all but one (92%) seroconverted to measles. The geometric mean titer of measles virus neutralizing antibody increased from 171 to 724 and the greatest increases occurred in those with the lowest pre-immunization titers. Moderate increases in levels of total IgM, IgG and IgE were detected in those with increases in antibody to measles virus. After reimmunization leukocyte counts decreased significantly from (5.8 x 10(6))+/-2.3 to (3.4 x 10(6))+/-0.7 ml(-1) (P=0.0001). The percentages of both CD4(+) and CD8(+) T cells decreased while the CD4:CD8 ratio remained unchanged. The percentage of CD56(+) natural killer (NK) cells increased from 5.2+/-2.7 to 7.2+/-2.8 (P=0.01). Functional assays showed improved lymphoproliferation in response to stimulation with phytohemagglutinin and tetanus toxoid and stable NK lytic activity. Therefore, reimmunization was accompanied by decreased leukocyte counts, but leukocyte function was unchanged or improved.

Antibodies, Viral↗

Effects of immunization of mothers on the immune reaction of their offspring: inhibition of immune responses of offspring caused by antibody imported through the milk.

Effects of immunization of pregnant AKR mice with nucleated chicken erythrocytes (CRBC) on immune responses of their offspring were examined. Antigen-specific reduction of generation of cytotoxicity and plaque forming cells (PFC) was demonstrated in the offspring at 8 weeks after birth, and lasted for 15 weeks. Cross-fostering experiments and cell transfer experiments showed that such suppression would be induced by antibody contained in the milk of immunized mothers rather than suppressor cells. Activities to enhance opsonization and to mediate antibody-dependent cell-mediated cytotoxicity (ADCC) were demonstrated in the serum of such offspring before challenge with CRBC. Delayed footpad reaction (DFR) was maintained at the normal level in such offspring of immunized mice.

Animals↗

Studies on immunity in hybridoma-bearing mice. B. Immunity against the hybridoma. I. Studies on the immune state of mice after rejection of the hybridoma.

Anti-dinitrophenyl IgE secreting hybridoma B 53 cells may be rejected when injected subcutaneously in BALB/c mice. These mice are immune as they withstand without any ill effect the intraperitoneal injection of LD100 B 53 cells. Sera from mice which rejected the tumor have cytotoxic antibodies against the hybridoma, as shown by in vitro tests, but serum cannot transfer immunity to naive BALB/c mice against hybridoma B 53. Spleen cells from mice which have rejected the tumor might transfer immunity against B 53 hybridoma, and with Winn tests it has been shown that these spleen cells are very effective against the B 53 cells and also against the myeloma cells which were used for the fusion to construct the B 53 hybridoma. Subcutaneously injected B 53 cells not only produce anti-DNP IgE secreting tumors, but often also metastasize to spleen, and they are sometimes detected in the circulating blood. Mice with splenic metastasis or with detectable circulating B 53 cells generally die. However, we did observe one mouse with splenic metastasis which successfully rejected the tumor and became immune to B 53 cells.

Animals↗

A 2-year follow-up of an anti-HIV immune reaction in HIV-1 gp160-immunized healthy seronegative humans: evidence for persistent cell-mediated immunity.

The first trial of an anti-HIV immunization, using a recombinant vaccinia virus expressing gp160 (rV) for priming and paraformaldehyde-fixed rV-infected PBLs and soluble gp 160 for boosting, clearly showed an in vitro HIV-protective immune reaction. This result led us to carry out an additional 2 year Phase I clinical trial in 25 HIV-seronegative volunteers, using HIV gp 160 antigens for immunization in four different protocols. The 2 year trial showed (a) the safety of the preparations, (b) a transient humoral immunity following each boost, and (c) a long-lasting memory T-cell response. Memory cytotoxic T-lymphocytes (CTLs) induced by gp 160 antigen with or without vaccinia vector lysed HLA class I restricted target cells expressing HIV-1 env antigens. These results are consistent with CTLs being an effective component of an AIDS vaccine to control cell-to-cell viral replication, dissemination in the organism, and subsequent evolution toward AIDS.

AIDS Vaccines↗

The immune system and intravenous administration of immune globulin. Part I, The immune system.

Interest in the immune response has greatly increased, mostly because of the discovery of the AIDS virus. An understanding of the basic function of the normal human immune system is vital knowledge for today's nurse. Part 1 of this article describes normal immune response as well as abnormal immune system function, and correlates this information with the clinical picture of the patient.

Antibody Formation↗

Passive immunization reduces immunity that results from simultaneous active immunization against tick-borne encephalitis virus in a mouse model.

Concomitant administration of an antigen and antibodies of the respective specificity has been shown to result in reduced levels of actively produced antibodies. This has also recently been observed in a clinical trial on simultaneous passive and active immunization against tick-borne encephalitis virus (TBEV). In the current study the influence of simultaneous passive and active immunization on vaccine induced protective immunity against TBEV has been evaluated in a mouse model. Two immunizations with licensed whole-killed TBEV vaccines gave close to complete protection. Administration of human or mouse TBEV antibodies together with the first vaccine dose resulted in a significant reduction of vaccine induced protection against TBEV challenge. This effect was even more pronounced than that observed earlier on the levels of vaccine induced antibody.

Animals↗