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Rubella immunity in older children, teenagers, and young adults: a comparison of immunity in those previously immunized with those unimmunized.

Because rubella continues to be a common illness in adolescents and young adults and because it has been suggested that booster rubella immunizations should be performed, we studied antibody prevalence in 459 predominantly adolescent patients in a pediatric group practice. Rubella antibody (PHA titer greater than or equal to 1:13.5) in previously immunized patients (89.6% of 385) was significantly more common than antibody in unimmunized patients and patients with a questionable history of immunization (70.3% of 74) (P less than 0.005). Twenty-three seronegative patients with a documented history of prior immunization were reimmunized and 22 had an IgG (secondary) antibody response and only one an IgM (primary) antibody response. Since all but one of our patients with previous immunization had a secondary immune response following revaccination, it seems likely that the level of protection in previously vaccinated individuals is considerably greater than 90%. Attention today should be directed at finding and immunizing unvaccinated teenagers and young adults and not in major booster vaccine programs.

Adolescent↗

Effect of pre-existing immunity for systemic and mucosal immune responses to intranasal immunization with group B Streptococcus type III capsular polysaccharide-cholera toxin B subunit conjugate.

The effects of priming with a group B Streptococcus type III capsular polysaccharide (GBS CPS III)-recombinant cholera toxin B subunit (rCTB) conjugate, purified GBS CPS III or rCTB alone on the systemic and mucosal immune responses to CPS III after intranasal (i.n.) immunization were investigated in mice. Priming with purified GBS CPS III followed by boosting with GBS CPS III-rCTB conjugate or priming with the conjugate followed by boosting with free CPS induced comparable levels of specific IgG and IgA in both serum and in lungs and vagina. However, i.n. immunization comprising both priming and boosting with conjugate was superior to priming with CPS and boosting with conjugate or the reverse, especially with regard to inducing mucosal IgA anti-CPS responses. All the immunization schemes, except priming and boosting with free CPS, induced high and similar levels of IgG1 in serum. In contrast, mice primed with free CPS III and then boosted with CPS III-rCTB conjugate by the i.n. route failed to produce significant levels of IgG2a, IgG2b and IgG3 in serum, at difference from mice primed with the conjugate and boosted with either conjugate or free CPS. Pre-immunization with rCTB either i.n. or i.p. did not suppress specific serum IgG responses induced by GBS CPS III-rCTB conjugate intranasally, but did inhibit serum and especially mucosal IgA responses. Our findings suggest that priming with CPS affects the distribution of IgG subclasses to GBS CPS and that pre-existing anti-carrier rCTB immunity can have an inhibitory effect on mucosal immune responses elicited by the conjugate vaccine given by the i.n. route.

Administration, Intranasal↗

[New aspect of immune system: innate immunity and acquired immunity].

Recently, it has been turned out that our internal defense system is composed of two distinct components; innate/natural immune system and acquired/adaptive immune system. The former innate immunity is principally located at the surface area such as skin and mucosal compartment, while the latter acquired immunity is observed mainly in the circulating blood and lymphoid organs. The critical difference between those two systems exists in the receptors as well as their ligands. Rearranged gene-derived receptors like immunoglobulin (Ig) and MHC molecule-restricted alphabeta-type of T-cell receptors (TCR) with high specificities and memories are used to recognize peptide antigens in the acquired immunity, whereas non-rearranged invaliant receptors such as toll-like receptors (TLR), gammasigmaTCR and CD1 molecule-restricted alphabeta TCR are employed to detect lipid/glycolipid or nucleic acid-related antigens in the innate immunity. Based on such new findings, the actual roles of immunity are discussed.

Animals↗

Specific immune response genes of the guinea pig. V. Influence of the GA and GT immune response genes on the specificity of cellular and humoral immune responses to a terpolymer of L-glutamic acid, L-alanine, and L-tyrosine.

The ability of guinea pigs to make immune responses to the random linear copolymer of L-glutamic acid and L-alanine, GA, and to L-glutamic acid and L-tyrosine, GT, is each controlled by a different immune response gene. On the other hand, the random linear terpolymer of L-glutamic acid, L-alanine, and L-tyrosine, GAT, which contains both GA and GT antigenic determinants, is immunogenic in all guinea pigs. After GAT immunization, all animals develop delayed hvpersensitivity and serum antibody specific for GAT. However, only those guinea pigs possessing the GA immune response gene demonstrate cross-reactive delayed hypersensitivity when challenged with GA. In addition, the anti-GAT antisera produced by those animals having the GA gene contain cross-reacting anti-GA antibodies. The sera from guinea pigs lacking the GA gene have no anti-GA antibody activity. Thus, we have demonstrated that a specific immune response gene controlling responsiveness to a "simple" antigen can determine the specificity of both cellular and humoral immune responses to a more complex antigen.

Alanine↗

Immunization status and reasons for immunization delay among children using public health immunization clinics.

OBJECTIVES: To determine whether children attending our local health department clinics were being immunized in a timely manner, and to investigate the reasons for children not being immunized on schedule. DESIGN: Cross-sectional research design. SETTING: Five Salt Lake City/County Health Department immunization clinics in Utah. PARTICIPANTS: All patients presenting to the clinics for immunization from November 1990 to March 1991 when minor illness is prevalent. INTERVENTIONS: Data were gathered through interview and questionnaire. MEASUREMENTS/MAIN RESULTS: Children were mostly white; they came from two-parent households with reasonably high incomes and high parental education level. Only four children were denied vaccination, all for inappropriate timing. None were denied for illness. More than 75% had postponed bringing their children in for immunization. The most common reason given for delay was minor illness in the child. CONCLUSION: Even in this "low-risk" population, parental misperception regarding immunizations is a significant, contributing factor to low immunization rates. Public educational programs directed at increasing parental knowledge must be developed.

Child, Preschool↗

Transcutaneous immunization induces mucosal and systemic immunity: a potent method for targeting immunity to the female reproductive tract.

Female BALB/c mice were immunized with tetanus toxoid (TT) admixed with cholera toxin by direct application to shaved skin (Transcutaneous immunization, TCI). Tetanus toxoid-specific IgG and IgA in serum, saliva, vaginal lavage and fecal pellets were assayed by ELISA. Tetanus toxoid specific antibody-secreting cell (ASC) numbers were also determined by immunohistochemistry in sections of vagina, uterus, salivary gland and small intestine of immunized mice. TCI elicited significant levels of TT-specific IgG in serum, saliva and vaginal lavage, with the greatest increases over background seen in saliva (80-400 fold) and vaginal lavage (2-87 fold). TCI induced only modest levels of IgA in any of the samples tested (range 2-7 fold increase). In the absence of cholera toxin, application of TT alone did not result in detectable TT-specific antibodies in mucosal secretions. ASCs were found in all tissues following TCI. Cells were most frequent in uterus and vaginal tissues with ASC numbers less frequent in small intestine and salivary gland. This suggests that local production, rather than transudation from serum, is a major contributor of antibody in reproductive tract secretions. Further studies focussed on the role of sex hormones and immune induction following TCI. Animals immunized at the stage of oestrus cycle at which estrogen is abundant (Estrus), showed significantly lower levels of TT-specific IgG in vaginal lavage samples. Collectively, these data confirm the findings of Glenn and colleagues (1998), who showed TCI using cholera toxin can elicit high levels of serum IgG to both the toxin and co-administered antigen and further demonstrates that this route of immunization is particularly effective at eliciting humoral immunity in saliva and in the female reproductive tract.

Animals↗

Rectal immunization of mice with hepatitis A vaccine induces stronger systemic and local immune responses than parenteral immunization.

Systemic (spleen cell (SPLC), serum antibodies) and intestinal mucosal (Peyer's patch cells (PPC), lamina propria lymphocytes (LPLs), coproantibodies) immune responses were compared in mice immunized with varying doses (144, 72, 36, 18 ELISA units [EU]) of HAVRIX, an alum-adsorbed killed hepatitis A virus (HAV) vaccine, delivered either intrarectally (i.r.) or intraperitoneally (i.p.) in three doses at weekly intervals. HAV-specific IgG, IgM, and IgA antibody responses were evaluated by ELISPOT and EIA and HAV-responsive lymphocytes by lymphocyte stimulation assays. Systemic IgG responses were greater in mice immunized intraperitoneally with 144, 72, and 36EU of HAVRIX, while IgM and IgA responses were greater in PPC and LPL cell populations, serum and coproantibodies of rectally immunized mice, particularly at HAVRIX doses of 36 and 18EU. Rectal immunization at lower doses (36, 18EU) also elicited strong cellular responses in all cell populations while parenteral (i.p.) vaccination, did not. Results suggest that rectal immunization may be a highly effective way of inducing both local and systemic immunity to HAV.

Administration, Rectal↗

Immune response at birth, long-term immune memory and 2 years follow-up after in-utero anti-HBV DNA immunization.

Infections occurring at the end of pregnancy, during birth or by breastfeeding are responsible for the high toll of death among first-week infants. In-utero DNA immunization has demonstrated the effectiveness in inducing specific immunity in newborns. A major contribution to infant immunization would be achieved if a vaccine proved able to be protective as early as at the birth, preventing the typical 'first-week infections'. To establish its potential for use in humans, in-utero DNA vaccination efficiency has to be evaluated for short- and long-term safety, protection at delivery, efficacy of boosts in adults and effective window/s for modulation of immune response during pregnancy, in an animal model suitable with human development. Here we show that a single intramuscular in-utero anti-HBV DNA immunization at two-thirds of pig gestation produces, at birth, antibody titers considered protective in humans. The boost of antibody titers in every animal following recall at 4 and 10 months demonstrates the establishment of immune memory. The safety of in-utero fetus manipulation is guaranteed by short-term (no fetus loss, lack of local alterations, at-term spontaneous delivery, breastfeeding) and long-term (2 years) monitoring. Treatment of fetuses closer to delivery results in immune ignorance without induction of tolerance. This result highlights the repercussion of selecting the appropriate time point when this approach is used to deliver therapeutic genes. All these findings illustrate the relevance of naked DNA-based vaccination technology in therapeutic efforts aimed to prevent the high toll of death among first-week infants.

Animals↗

Immunization coverage and risk factors for failure to immunize within the Expanded Programme on Immunization in Kenya after introduction of new Haemophilus influenzae type b and hepatitis b virus antigens.

BACKGROUND: Kenya introduced a pentavalent vaccine including the DTP, Haemophilus influenzae type b and hepatitis b virus antigens in Nov 2001 and strengthened immunization services. We estimated immunization coverage before and after introduction, timeliness of vaccination and risk factors for failure to immunize in Kilifi district, Kenya. METHODS: In Nov 2002 we performed WHO cluster-sample surveys of >200 children scheduled for vaccination before or after introduction of pentavalent vaccine. In Mar 2004 we conducted a simple random sample (SRS) survey of 204 children aged 9-23 months. Coverage was estimated by inverse Kaplan-Meier survival analysis of vaccine-card and mothers' recall data and corroborated by reviewing administrative records from national and provincial vaccine stores. The contribution to timely immunization of distance from clinic, seasonal rainfall, mother's age, and family size was estimated by a proportional hazards model. RESULTS: Immunization coverage for three DTP and pentavalent doses was 100% before and 91% after pentavalent vaccine introduction, respectively. By SRS survey, coverage was 88% for three pentavalent doses. The median age at first, second and third vaccine dose was 8, 13 and 18 weeks. Vials dispatched to Kilifi District during 2001-2003 would provide three immunizations for 92% of the birth cohort. Immunization rate ratios were reduced with every kilometre of distance from home to vaccine clinic (HR 0.95, CI 0.91-1.00), rainy seasons (HR 0.73, 95% CI 0.61-0.89) and family size, increasing progressively up to 4 children (HR 0.55, 95% CI 0.41-0.73). CONCLUSION: Vaccine coverage was high before and after introduction of pentavalent vaccine, but most doses were given late. Coverage is limited by seasonal factors and family size.

Child Health Services↗

Prophylactic immunization against experimental leishmaniasis. IV. Subcutaneous immunization prevents the induction of protective immunity against fatal Leishmania major infection.

Durable immunity against fatal L. major infection in genetically susceptible mice can be induced by immunization with 150,000-rad irradiated or heat-killed promastigotes administered i.v. or to a lesser extent i.p. Conversely, subcutaneous (s.c.) and intramuscular (i.m.) injections are not only totally ineffective but generally increase susceptibility to and enhance the progression of the disease, leading to earlier mortality. This detrimental effect is particularly evident with lower infecting challenge doses. Disease exacerbation is apparent in mice given 4 X s.c. injections of as few as 2 X 10(4) irradiated promastigotes, but it appears most potent after doses of 2 X 10(7). When mice given 4 X s.c. injections were subsequently immunized i.v. with 2 X 10(7) irradiated promastigotes, they failed to develop any evidence of protection against infection with 2 X 10(5) promastigotes, whereas mice given i.v. immunization alone were strongly protected. Thus, s.c. injections are capable of blocking the prophylactic effect of i.v. immunization with irradiated parasites. This inhibitory effect can be achieved with a single s.c. injection, although rather less potently than with four, and is even effective against four repeated weekly i.v. immunizations. Once induced, the effect persists undiminished after 100 days. A weaker effect is also inducible by s.c. injection given after i.v. immunization. The blocking effect of s.c. injection is not dependent on continuing viability of the promastigotes, as it can be induced equally readily with heat-killed, formalin-fixed, or sonicated parasites. The phenomenon extends to mouse strains genetically resistant as well as susceptible to L. major infection and, in congenic mice of BALB background, is independent of the major histocompatibility (H-2) gene complex.

Animals↗

Immune complexes in the spleen. Replacement of immune complexes trapped in spleen follicles by new immune complexes from the circulation.

The fate of intravenously injected 125I-BGG-anti-BGG in the spleen of mice was studied using autoradiography. Part of the labelled immune complexes was trapped in the follicles of the spleen as could be expected. In a first experiment it was found that injections with unlabelled immune complexes were followed by a partial release of the labelled immune complexes from the follicles. In a second experiment unlabelled immune complexes retained in spleen follicles appeared to inhibit the trapping of intravenously injected labelled immune complexes to some degree and for some time. The conclusion was drawn from these experiments that immune complexes, which normally remain in part of the lymphoid follicles for a long period, may be replaced by new immune complexes from the circulation. This seems important since trapping in lymphoid follicles of antigen complexed by antibody is the only known mechanism by which small amounts of antigen may be preserved in the body for a long time after the initiation of antibody production. The bulk of antigen and antigen-antibody complexes is removed by phagocytosis followed by destruction. It appeared also that, although all spleen follicles in the mouse spleen is able to retain the complexes for a longer time. Possible explanations for these individual differences between the follicles of one spleen are discussed.

Animals↗

Immune complexes in pregnancy. III. Immune complexes in immune complex-associated conditions.

Seventeen patients during the third trimester of pregnancy with associated immune complex disease and/or immune complex state and their infants' cord blood were investigated for the presence of immune complexes. In comparing maternal levels of immune complex in normal third-trimester pregnancies to the study group, no statistical significant difference was noted. However, levels in cord blood were significantly lower (p less than 0.0025) than levels in paired maternal samples, but were found to correlate significantly (p less than 0.002). On the basis of the immunochemical analysis of selected pairs, the conclusion is that IgG-containing immune complexes may be responsible for this observed correlation and may represent the normal physiologic situation of pregnancy, whereas IgM-containing immune complexes may represent pathologic, and, therefore, abnormal, states. The suggestion is that the presence of such IgM-containing immune complexes may become predictive of fetoplacental compromise.

Antigen-Antibody Complex↗

Immunity to Toxoplasma gondii induced in vitro in non-immune mouse macrophages with specifically immune lymphocytes.

Male and female CBA mice were used to study in vitro the mechanisms involved in the development and expression of cellular immunity to toxoplasma infection. The lag phase preceding toxoplasma division was delayed in nonimmune macrophages obtained from peritoneal cavities stimulated with thioglycollate. Specific anti-toxoplasma activity was conferred on nonimmune macrophages incubated with toxoplasma-immune spleen lymphocytes and soluble toxoplasma antigen. Treatment of immune spleen cell populations with anti-theta serum plus complement abolished completely their activity of conferring anti-toxoplasma activity on nonimmune macrophages, demonstrating that the essential cells were T lymphocytes. The mediator(s) responsible for the acquisition of immunity to toxoplasma in the nonimmune macrophages were soluble. Heat-inactivated, toxoplasm-immune macrophages of fibroblasts. The findings are related to previous investigations of induced immunity in animals and man.

Animals↗

Maternal HEL immunization has no lasting effects on the immune response of offspring to immunization with hen egg-white lysozyme.

The effect of prior maternal immunization on the murine offspring response to subsequent immunization with hen egg-white lysozyme was examined. Adult female A/J mice were immunized with 100 micrograms HEL-CFA intraperitoneally 10-27 weeks before conception. The offspring of these experimental female mice were then immunized with HEL-CFA at differing ages. Suppression of the anti-HEL IgG B cell response was observed when the offspring were immunized prior to 3 weeks of age when high levels of maternal antibody were still present. Older offspring, more than 8 weeks of age, were immunized with HEL-CFA to determine if exposure to maternal immunoglobulin early in ontogeny had primed or altered the offspring response to HEL. At this age, suppressive effects of transferred maternal antibody were no longer evident. Priming was not detected in the offspring as judged by the total magnitude of the anti-HEL antibody response or the kinetics of the response when experimental and age-matched control offspring were examined. Furthermore, qualitative differences in the response as evidenced by IgG vs IgM content and fine specificity of the response (primary vs secondary antibody) were not observed. No evidence was found to suggest that exposure to polyclonal maternal anti-HEL antibody had primed the offspring for a more efficient or qualitatively different response to immunization with the protein antigen HEL. After maternal antibody levels decreased, the offspring response was similar to that of controls, suggesting that the response had not been permanently altered by the prior exposure early in ontogeny to polyclonal maternal antibody.

Animals↗

Kinetics of the immune response after primary and booster immunization against tick-borne encephalitis (TBE) in adults using the rapid immunization schedule.

UNLABELLED: A total of 222 adult subjects aged 19-51 years were enrolled in this multi-center, phase III study to evaluate immunogenicity and safety of the first booster immunization with a new tick-borne encephalitis (TBE) vaccine. This was an extension study that followed subjects who had received primary immunization 12-18 months previously with either the new or formerly licensed TBE vaccine according to the rapid immunization schedule (i.e. on Days 0, 7 and 21). Compared to the levels of primary immunization, prior to first booster, neutralizing TBE antibodies (geometric mean titers, GMTs) of both vaccination groups had remained on a high level and were far above the detection limit of the neutralization test used. All subjects showed a sharp increase of TBE antibodies following the booster. The booster was well tolerated by the subjects. CONCLUSION: These results in terms of both immunogenicity and safety indicate that the TBE vaccination with this new TBE vaccine can be used effectively and safely in adults. A long lasting immunity can be concluded from the strong immune response following the first booster.

Adult↗

Genetic control of immunity to parasites: adoptive transfer of immunity between inbred strains of mice characterized by rapid and slow immune expulsion of Trichinella spiralis.

Adoptive transfer of immunity with immune mesenteric lymph node cells (IMLNC) was used to analyse the roles of immune and inflammatory events in determining the strain-characteristic time of expulsion of Trichinella spiralis from mice. Transfer of IMLNC within and between three rapidly responding strains (NIH, SWR, DBA1-all H-2q) resulted in accelerated worm expulsion, worm loss commencing before day 8 in each case. When NIH cells were transferred to slow-responder B10 congenic mice (B10G-H-2q) mice, immunity was evident at 8 days as a reduction in worm fecundity and only by 12 days as a reduction in worm numbers. A similar result was obtained when B10G cells were given to B10G recipients. In the reciprocal transfer, IMLNC from B10G transferred immunity to NIH as effectively and as rapidly as did NIH cells. Cells capable of transferring immunity were present in B10G mice as early as 4 days after infection, even though worm expulsion in this strain does not occur until after day 12. Thus following heterologous transfers of IMLNC, the time of worm expulsion was determined by the response of the recipient, and presumably by the ability to generate intestinal inflammatory changes. Earlier work has shown that the strain-characteristic time of worm expulsion is genetically determined, but not by H-2 linked genes. A corollary of the present work is that non-H-2 linked genes control the generation of intestinal inflammatory changes in T. spiralis infections. H-2 genes may control lymphocyte responsiveness to infection and the haplotype H-2q may determine a rapid response. Comparisons are made with the genetic control of resistance to Listeria monocytogenes and possible mechanisms are discussed.

Animals↗

Antigen detection in vivo after immunization with different presentation forms of rabies virus antigen, II. Cellular, but not humoral, systemic immune responses against rabies virus immune-stimulating complexes are macrophage dependent.

In this paper we describe the effect of depletion of splenic macrophages on the uptake, and immune response against, different formulations of rabies virus antigen. Splenic macrophages were removed by intravenous injection with clodronate liposomes. beta-propiolacton inactivated rabies virus (RV-BPL) and immune-stimulating complexes (iscom) containing these antigens were given to macrophage-depleted and control mice. In the absence of phagocytic cells in the spleen, antigen is still trapped in the red pulp and to a lesser extent in the peri-arteriolar lymphocyte sheaths (PALS) for both antigen formulations. The localization pattern in the main area of immune response induction, namely the follicles, was unaltered after macrophage depletion. Functionally, the depletion of splenic and liver macrophages had no influence on the induction of specific antibody responses in both RV-BPL or RV-iscom immunized mice, even though the latter presentation form was clearly associated with specific localization in the marginal metallophillic macrophages. In RV-BPL immunized mice, macrophage depletion had no influence on proliferative T-cell responses. However, macrophage-depleted mice that were immunized with RV-iscom showed a significant decrease in proliferative T-cell responses. These results confirm existing ideas on the spleen as a physical filter rather than an induction site for humoral responses and shed new light on the efficient role of iscoms as antigen-presenting moieties in relation to their specific in vivo localization patterns and partial macrophage dependency.

Animals↗