Primary Antibody Response Research Articles

Ciprofloxacin enhances T cell function by modulating interleukin activities

Ciprofloxacin (CIP) is a quinolone carboxylic acid derivative with a broad spectrum of antibacterial activity. CIP (0.1-30 micrograms/ml) enhanced DNA synthesis of mouse spleen cells and human peripheral blood lymphocytes (PBL) that had been activated with T cell mitogens or with alloantigens. In addition, CIP increased the amount of IL-2 found in the supernatants of phytohaemagglutinin (PHA)-stimulated human PBL. The presence of CIP in the medium (0.3-10 micrograms/ml) increased the levels of IL-1 found in the culture supernatants of adherence-enriched mouse macrophages, human monocyte/macrophages and a human monocytic cell line stimulated with lipopolysaccharide. In contrast there was no effect of CIP on the release of IL-1 by freshly isolated human monocytes or by cells of the keratinocyte line, A431. CIP alone had no influence on the basal release of IL-2 by NOB-1 cells, a T cell line that responds to IL-1 with an increase in IL-2 synthesis, but, in combination with recombinant IL-1, CIP significantly enhanced the release of IL-2 by these cells. The results of this study suggest that CIP modulates the immune response at two levels--the production of IL-2 by activated T cells and the production of IL-1 by activated monocyte/macrophages. However, CIP did not affect the primary antibody response in vitro or in vivo against sheep erythrocytes and ovalbumin respectively. Thus the enhancing action of ciprofloxacin on the immune system appears to be restricted to T cell function and macrophage/T cell interactions.

IL-2 infusion abrogates humoral immune responses in humans.

Although IL-2 infusion enhances cell-mediated cytotoxicity in patients with neoplastic disease, administration is paradoxically associated with a modest fall in total serum IgG and an increased risk of infection. We now show that the adverse effects of IL-2 infusion on the humoral immune system are substantial. Although IL-2 induces the B cell growth and differentiating factors IL-4 and IL-6, infusion abrogates primary antibody responses entirely and reduces secondary antibody responses 50-fold following antigen challenge. There is no evidence of the generation of cells with suppressive activity on B cells but IL-2 increases the ratio of circulating virgin:memory cells. These results may help to explain the increased rate of bacterial infection in patients receiving IL-2. As IL-2 plays a central role in the generation of an immune response, the finding that it is also sufficiently immunosuppressive to inhibit primary- and secondary-type antibody responses suggests that exploration of the underlying mechanisms may provide insights into immune system homeostasis and may offer new approaches to therapeutic immunosuppression.

An immunosuppressive murine leukaemia virus induces a Th1-->Th2 switch and abrogates the IgM antibody response to sheep erythrocytes by suppressing the production of IL-2.

Many retroviruses have tropism for cells in the immune system and have a propensity to induce immunosuppression in the host. Some of the effects of retroviruses on immune cell function are thought to be mediated through cytokines. Friend ImmunoSuppressive virus-2 (FIS-2) is a low oncogenic murine leukaemia virus (MuLV) that induces lymphadenopathy and immunosuppression in NMRI mice. The role of T cell cytokines during the generation of a primary antibody response in healthy and FIS-2-infected mice was studied following the antibody response to sheep erythrocytes by an in vitro immunization (IVI) technique. In cultures from FIS-2-infected mice, the antibody response was reduced compared with cultures from uninfected mice and the production of the Th2 cytokines IL-4 and IL-6 was elevated, whereas the Th1 cytokines IL-2, interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) were reduced. The suppressed anti-sheep erythrocyte antibody response in cultures from mice infected with FIS-2 seemed to be caused by an insufficient production of IL-2, since addition of recombinant IL-2 stimulated the antibody response. This effect was also observed in cultures depleted of T cells, indicating a direct effect of IL-2 on B cells. A switch to a Th2 cell response and suppression of IL-2 production might play a central role in the immune cell dysfunction induced by FIS-2.

Does an alloimmune response to strong immunogenic red blood cell antigens enhance a response to weaker antigens?

It has been suggested that an immune response against the high immunogenic D antigen also augments the immune response to less immunogenic red blood cell (RBC) antigens. Based on the high antibody frequency, E and K antigens can also be regarded as strong immunogens. The question is whether the immunization against E and K antigens also enhances the formation of other antibody specificities. This question is in particular relevant for patients who are currently transfused with RH- and/or K-matched RBCs. A retrospective multicenter study analyzed FY, JK, and MNS antibodies alone and in combination with anti-E and/or anti-K. Analysis was performed for primary and subsequent antibody responses. In the cohort analyzed, 5016 patients possessed 5981 antibodies. Antibodies directed to multiple blood group systems were present in 606 of the 779 (78%) patients with multiple antibodies. In 88 of 1270 (6.9%) patients, FY, JK, and/or MNS antibodies appeared simultaneous with anti-E and/or anti-K during a primary antibody response after transfusion. Patients formed antibodies to antigens in the FY, JK, and MNS systems equally often as first antibodies followed by anti-E or anti-K than as second antibodies after anti-E or anti-K were already present. Patients with anti-E and/or anti-K or with antibodies to antigens in the FY, JK, and/or MNS systems equally often formed additional antibodies during a second antibody response. An immune response against allogeneic RBC antigens defines good responders who readily form antibodies against other antigens. No support was found that the response against strong RBC antigens also enhances the formation against weaker antigens.

61. Gene expression profiling in the stressed spleen: Dissecting stress-induced suppression of the primary antibody response

61. Gene expression profiling in the stressed spleen: Dissecting stress-induced suppression of the primary antibody response

Type I interferons as vaccine adjuvants against infectious diseases and cancer

Presently, new attention is given to type I interferons (IFNs) as essential factors linking innate and adaptive immunity. Several studies provided evidence about the importance of IFN-α in the differentiation of the Th1 subset, in the generation and activity of cytotoxic T lymphocytes, in the enhancement of a primary antibody response and in the activation of dendritic cells. Owing to their immunomodulatory properties, type I IFNs can represent good candidates to be used as adjuvants for vaccination. In the present review, we summarize recent studies in humans and in animal models, suggesting a possible application of type I IFNs as adjuvants for the development of more effective vaccines against infectious diseases and cancer.

Genetic parameters for body weights, egg traits and antibody response against Newcastle Disease Virus (NDV) vaccine among two Tanzania chicken ecotypes

Genetic parameters were estimated for production traits and primary antibody response (Ab) against Newcastle diseases virus (NDV) vaccine among two Tanzania chicken ecotypes viz. Kuchi and Tanzania Medium (Medium). Production traits studied were body weights at 8 (Bwt8), 12(Bwt12), 16(Bwt16), and 20 (Bwt20) weeks of age, age at first egg (AFE), egg number in the first 90 days after sexual maturity (EN-90), egg weight (EW), egg shell thickness (STH), and egg shape index (ESI). Heritability estimates for Bwt8, Bwt12, Bwt16, Bwt20, AFE, EN-90, EW, STH, ESI and Ab for Kuchi chicken were 0.38 +/- 0.10, 0.41 +/- 0.07, 0.44 +/- 0.08, 0.45 +/- 0.09, 0.42 +/- 0.10, 0.31 +/- 0.05, 0.43 +/- 0.08, 0.53 +/- 0.11, 0.48 +/- 0.13 and 0.27 +/- 0.06, respectively. Corresponding estimates for Medium ecotype were 0.39 +/- 0.09, 0.43 +/- 0.10, 0.42 +/- 0.08, 0.43 +/- 0.07, 0.52 +/- 0.11, 0.32 +/- 0.06, 0.50 +/- 0.07, 0.61 +/- 0.13, 0.52 +/- 0.10 and 0.29 +/- 0.05, respectively. Genetic (r (g)) and phenotypic (r(p)) correlations in both ecotypes were highest among body weights (i.e. r(g) = 0.60 to 0.93 and r(p) = 0.54 to 0.78), and were lowest (around 0.10 and below, ranging from positive to negative) among primary antibody response against NDV vaccine and production traits, and among eggshell thickness, egg shape index and other production traits. The magnitudes of heritability estimates obtained in this study indicate good prospects of improving these traits in both ecotypes through selection.

Association of LEI0258 microsatellite alleles with antibody response against newcastle disease virus vaccine and body weight in two Tanzania chicken ecotypes

A study was carried out to evaluate the prospects of using marker assisted selection (MAS) in improving primary antibody response against Newcastle disease virus (NDV) vaccine and body weight in two Tanzania chicken ecotypes, namely Kuchi and Tanzania Medium (Medium). The study involved evaluation of the association between LEI0258 microsatellite alleles (a microsatellite located within the chicken Major Histocompatibility Complex) and primary antibody response and body weight. Results indicated that the allele 205 bp was significantly (P primary antibody responses against NDV vaccine, while the allele 307 bp was significantly (P<0.05) negatively associated with this trait. The allele 307 bp was also significantly (P<0.05) positively associated with body weight. However, based on the magnitude of R2 (which were less than 0.10), it was envisaged that incorporation of these alleles into breeding programs would results into marginal response and hence their use in resource poor countries may sometimes not be justified. Therefore use of cheaper methods for the chicken MHC typing was recommended.

Cardiovascular exercise intervention improves the primary antibody response to keyhole limpet hemocyanin (KLH) in previously sedentary older adults

Based upon a prior cross-sectional study, we hypothesized that an aerobic exercise intervention in sedentary older adults would improve a primary T cell-dependent immune response. Participants were a subset of older subjects from a large, ongoing exercise intervention study who were randomly assigned to either an aerobic exercise (Cardio, n = 30, 68.9 + 0.8 years) or flexibility/balance (Flex, n = 20, 69.9 + 1.2 years) intervention. The intervention consisted of either three aerobic sessions for 30–60 min at 55–70% VO 2max or two 60 min flexibility/balance sessions weekly for 10 months. Eight months into the intervention, samples were collected before intramuscular administration of KLH (125 μg), followed by sampling at 2, 3, and 6 weeks post-KLH. Serum anti-KLH IgM, IgG1, and IgG2 was measured by ELISA. Physiological and psychosocial measures were also assessed pre- and post-intervention. While there was no difference in the anti-KLH IgG2 response between groups, Cardio displayed significantly ( p < 0.05) higher anti-KLH IgG1 (at weeks 2, 3, and 6 post) and IgM responses when compared to Flex. Despite cardiovascular intervention-induced improvement in physical fitness (∼11% vs. 1% change in VO 2peak in Cardio vs. Flex, respectively), we found no relationship between improved fitness and enhanced anti-KLH antibody responses. Optimism, perceived stress, and affect were all associated with enhanced immune response. We have shown for the first time that cardiovascular training in previously sedentary elderly results in significantly higher primary IgG1 and IgM antibody responses, while having no effect on IgG2 production.

The effects of B‐cell depletion therapies on humoral immune responses in normal mice

Anti‐CD20 mediated B cell depletion is a therapy for treating rheumatoid arthritis and B‐cell malignancies. To examine how B cell depletion affects an individual's capacity to generate antibody responses we assessed in a mouse model primary and secondary antibody responses after treatment with anti‐mouse CD20 and/or BAFFR‐Ig. BALB/c mice dosed with anti‐CD20 one week prior to primary TNP‐KLH immunization had a 93% decrease in anti‐TNP IgG titers at day 10 compared to controls. Mice treated with anti‐CD20 one week prior to immunization with TNP‐Ficoll had a ~50% increase in TNP‐specific IgG and IgM titers. The secondary antibody response to TNP‐KLH was not significantly affected by anti‐CD20 treatment one week prior to immunization. BAFFR‐Ig treatment reduced the secondary response to TNP‐KLH by 57%. Treatment of mice with the combination of anti‐CD20 and BAFFR‐Ig dramatically reduced secondary antibody responses to either antigen. After B‐cell repopulation all treatment groups mounted a strong response to a tertiary challenge. Therefore, B cell depletion with anti‐CD20 results in a strong reduction in the primary antibody response to a neoantigen, however memory B cells appear resistant to anti‐CD20 treatment. Simultaneous anti‐CD20 and BAFFR‐Ig treatment results in elimination of the secondary response by blocking memory B cell activation but does not deplete memory B cells.

Rapid Decline of Influenza Vaccine–Induced Antibody in the Elderly: Is It Real, or Is It Relevant?

Advisory committees have cautioned that influenza vaccine-induced antibody declines more rapidly in the elderly, falling below seroprotective levels within 4 months. We conducted a literature review to assess this assertion. The articles that were included in this review reported antibody levels > or =4 months after influenza immunization in persons > or =60 years old, interpretable in the context of annual influenza vaccine-approval criteria (seroprotection/seroconversion) specified by the Committee for Proprietary Medicinal Products (CPMP) for the elderly. The final review included 14 studies; 8 of which reported seroprotection rates. Seroprotection exceeding CPMP criteria was maintained > or =4 months after influenza immunization in all 8 of the studies reporting this for the H3N2 component and in 5 of the 7 studies reporting this for the H1N1 and B components. In determining whether CPMP criteria were met at season's end, primary antibody response appeared to be more relevant than secondary antibody decline. Both studies reporting seroprotection rates that failed CPMP criteria > or =4 months after influenza immunization for each of the H1N1 and B components had also reported failed seroprotection at 1 month after immunization. If initially achieved after immunization, seroprotection rates of 70%-100% were maintained not just at 4 months (2 studies) but also at 5 months (2 studies) and even at >6 months (4 studies), for the H3N2 and H1N1 vaccine components. Seroprotection rates appeared less consistent for the B vaccine component, throughout the postimmunization period. Seroconversion appears to vary substantially and inversely with preimmunization titers but not with age. In 2 of 6 studies reporting seroconversion alone, CPMP criteria were still met at 4 months. In the other 4 studies, the main reason for failure at 4 months was primary failure at 1 month. A total of 6 studies compared antibody persistence by age, and no consistent differences were found on that basis. The historic concern that the influenza vaccine-induced antibody response in the elderly declines more rapidly and below seroprotective levels within 4 months of immunization should be reconsidered.

Correlated effects of selection for immunity in White Leghorn chicken lines on natural antibodies and specific antibody responses to KLH and M. butyricum

BackgroundThe effect of selection for three general immune response traits on primary antibody responses (Ab) to Mycobacterium butyricum or keyhole limpet hemocyanin (KLH) was studied in four experimental lines of White Leghorn chicken. Birds underwent 12 generations of selection for one of three different general immune criteria; high antibody response to Newcastle disease virus 3 weeks after vaccination (ND3), high cell-mediated immune response, using the wing web response to phytohemglutinin (PHA) and high phagocytic activity, measured as carbone clearance (CC). Line ND3-L was selected on ND3, line PHA-L was selected on PHA, and line CC-L on CC, but all lines were measured for all three traits. The fourth line was a contemporary random bred control maintained throughout the selection experiment. Principal component analysis was used to distinguish clusters based on the overall set of immune measures.ResultsIn the KLH immunised group, no differences were present between lines for natural antibodies binding to KLH and LPS, and, lines ND3-L and PHA-L had higher titers to LTA and anti-Gal titers measured before the immunisation protocol. The measure of ND3 was correlated positively with LPS titers measured post KLH immunisation and with the difference between LPS titers measured at day 0 and 7 post immunisation. In the M. butyricum immunised group, Line ND3-L showed significantly higher specific antibody response to M. butyricum, and this result agrees well with the hypothesis that the Th-1 pathway was expected to be selected for in this line.ConclusionThis study has shown that the two different antigens KLH and M. butyricum gave rise to different responses in the set of selected lines, and that the response was only enhanced for the antigen associated with the same response mechanism as that for the trait (ND3, PHA or CC) for which the line was selected. Interactions between innate and acquired immunity have been observed mainly for the high antibody selected trait, indicating there was a specific interaction due to the selection criterion. Furthermore, the results confirmed the independence between the three selected traits. Finally, principal component analysis contributed to visually discriminate high and low responders to the two new antigens in the four lines.

Stimulation of the primary anti-HIV antibody response by IFN-α in patients with acute HIV-1 infection

Type I IFNs are needed for the production of antiviral antibodies in mice; whether they also stimulate primary antibody responses in vivo during human viral infections is unknown. This was assessed in patients acutely infected with HIV-1 and treated with IFN-alpha2b. Patients with acute HIV-1 infection were randomized to receive antiretroviral therapy alone (Group A, n=60) or combined for 14 weeks with pegylated-IFN-alpha2b (Group B, n=30). Emergence of anti-HIV antibodies was monitored during 32 weeks by Western blot (WB) analyses of serum samples. IFN-alpha2b treatment stimulated the production of anti-HIV antibodies. On Week 32, 19 weeks after the last IFN-alpha2b administration, there were 8.5 (6.5-10.0) HIV WB bands (median, interquartile range) in Group B and 7.0 (5.0-10.0) bands in Group A (P=0.054), and band intensities were stronger in Group B (P<0.05 for p18, p24, p34, p40, and p55 HIV antigens). IFN-alpha2b treatment also increased circulating concentrations of the B cell-activating factor of the TNF family (P<0.001) and ex vivo production of IL-12 (P<0.05), reflecting its effect on innate immune cells. Withdrawal of antiretroviral treatment on Week 36 resulted in a lower rebound of HIV replication in Group B than in Group A (P<0.05). Therefore, type I IFNs stimulate the emerging anti-HIV immune response in patients with acute HIV-1 infection, resulting in an improved control of HIV replication. Type I IFNs are thus critical in the development of efficient antiviral immune responses in humans, including the production of antiviral antibodies.

Study of the Physiological Changes in Blood Chemistry, Humoral Immune Response and Performance of Quail Chicks Fed Supplemental Chromium

One hundred and fifty 2-week old Japanese quail chicks were allotted to 5 groups (30 chicks each) to investigate the effects of adding inorganic chromium (Cr) supplied from chromium chloride (CrCl , 6H O) 3 2 on some blood components, humoral immune responses and growth performance of growing quails. The dietary treatment was different dietary concentrations of Cr in the basal diet, to provide 0.0 (control), 125, 250, 375 and 500 μg / kg feed. Ten chicks per group, at 4 and 6 wk of age were injected intramuscularly with sheep red blood cells (SRBCs) to determining the primary and secondary antibody responses, respectively. Chromium supplementation significantly decreased the plasma levels of glucose, total cholesterol and total lipids, whereas total protein, globulin, AST and ALT increased. Plasma albumin concentration slightly but not significantly also increased. Dietary Cr caused a significantly increased in plasma level of Ca., but did not affect the plasma concentrate of P. In addition, supplementation with Cr significantly improved body weight, weight gain and feed conversion ratio compared to control. However, Cr administration did not affect the relative weights of any organ studied. With respect to humoral immune responses the results indicated that total antibody and IgG titers against SRBCs were significantly higher in chicks receiving Cr at low (125 μg/kg feed) and middle (250 μg/kg feed) doses compared with those of control at secondary immune responses. The results suggest that under condition of this experiment, Cr may play a part in carbohydrate; lipid and proteins metabolism in quail chicks and can used as additives in grower quail diets without side effects on the health of the bird.

Comparison of strain‐specific antibody responses during primary and secondary infections with respiratory syncytial virus

Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection in infants. RSV repeatedly reinfects individuals: this may be due in part to the variability of the attachment (G) glycoprotein and changes in this protein have been shown to be under positive selection. Infants experiencing their primary infection show a genotype-specific antibody response with respect to the variable regions of the G protein. A prospective study of RSV infections in a birth cohort in rural Kenya identified infants experiencing repeat infections with RSV. The serum antibody responses of these infants were investigated with respect to their anti-RSV reactions in an enzyme-linked immunosorbent assay (ELISA) and the specificity of the response to a variable region of the G protein by ELISA and immunoblotting using bacterially expressed polypeptides representative of the currently circulating strains of RSV. The results presented here confirm that the primary antibody response to the variable regions of the G protein is generally genotype-specific, but show that the response may become cross-reactive (at least within group A viruses) during secondary infections even where the secondary infection is of the same genotype as the initial infection. Also, some infants who did not mount a detectable antibody response to whole RSV antigens during their primary infection nevertheless showed genotype-specific responses to the G protein. In conclusion, the strain-specific nature of the serum antibody response to the variable regions of the G protein of RSV observed in primary infections can become cross-reactive in subsequent reinfections.

B lymphocyte physiology: the beginning and the end.

Whereas lymphatic tissues were implicated as the chief sites for antibody production almost 100 years ago, three findings cemented the role of the plasma cell as the actual producer, namely the histological and tissue culture studies of Fagraeus, the beautiful immunofluorescent approach of Coons and his group, and the micromanipulation approach to the study of antibody formation by single cells introduced by Lederberg and myself. Proof that antibody-forming cells derived from B, rather than T, cells had to await the studies of Miller and Mitchell, with some minor technical contributions from myself. The physiology of the germinal centre also has a long history, and recently much interest has surrounded the relative roles of germinal centres as sites of somatic immunoglobulin V gene hypermutation and selection of high affinity B cells, versus the roles of extra-follicular proliferative foci as sources of the primary antibody response. Tolerance and self-antigens within the primary B lymphocyte repertoire is secured by clonal deletion within the bone marrow of those cells which are operationally the most threatening to the body, and a second level of functional impairment of B cell activity and life-span, capable of being induced centrally or peripherally, termed clonal anergy. As these concepts became progressively more refined through transgenic models of immunological tolerance, we turned our attention more towards tolerance within the secondary B lymphocyte repertoire. This is generated primarily inside germinal centres, where it appears that two quite separate mechanisms act as a bulwark against the possible creation of hypermutated anti-self cells. The first is that germinal centre activity and memory cell generation are dependent on antigen-specific, germinal centre-seeking CD4+ T cells, and if a putative anti-self mutant B cell gets no help because of T cell tolerance, it will not expand further. The second is a very specific mechanism confined to the germinal centre whereby antigen-specific B cells are especially sensitive to antigen-induced apoptosis if soluble, deaggregated antigen is presented to them before they reach the 'rescue' signal of follicular dendritic-cell-bound antigen. While some of the death in germinal centres is clearly apoptotic in nature, a further phenomenon observed electron microscopically relates to the formation of type B dark cells. It is not yet clear whether the DNA in this type of dying cell is cleaved. Transgenic expression of bcl-2 in germinal centre B lymphocytes confers incomplete protection from apoptosis caused by soluble antigen. The suggestion that at least some of this apoptosis is mediated via Fas-Fas ligand interactions is prompted by the observation that the apoptotic phenomenon is markedly reduced in lpr mice.

Antibody Response Against Sheep Red Blood Cells in Lines Congenic for Major Histocompatibility (B) Complex Recombinants

Six congenic lines containing B complex recombinants R1 = B-F/B-L24, B-G23; R2 = B-F/B-L2, BG23; R3 = B-F/B-L2, B-G23; R4 = B-F/B-L2, B-G23; R5 = B-F/B-L21, B-G19; and R6R6 = B-F/B-L21, B-G23 were tested individually for antibody response against SRBC. R2, R3 and R4 arose from independent recombination events but are serologically identical. Each B complex recombinant was crossed to inbred Line UCD 003 (B17B17). After ten backcross generations to the inbred line, B complex heterozyogtes were mated to produce recombinant homozygous lines having 99.9% background gene uniformity. Birds of each line were injected intravenously with 1 mL of 2.5% SRBC at four and 11 weeks of age to induce primary and secondary antibody responses, respectively. Blood samples were collected 7 days post-injection. Microtiter methods were used to assay total anti-SRBC and mercaptoethanol-resistant (MER) serum antibody. All antibody titers were evaluated by least squares ANOVA with hatch and B recombinant genotype as main effects. Fisher’s protected LSD was used to evaluate significant means. Genotypes R5R5 and R6R6 had significantly higher primary total antibody titer to SRBC compared with R1R1, R2R2, R3R3 and R4R4. Both R5 and R6 have BF21, a haplotype known for high antibody response to SRBC. Primary MER antibody response did not differ significantly among the genotypes. The total and ME-resistant secondary antibody titers of R5R5 chickens were significantly higher than the other five recombinants. These results indicate that congenic lines carrying six B complex recombinants differ in their primary and secondary antibody responses to SRBC.

Resetting the Adaptive Immune System After Autologous Stem Cell Transplantation: Lessons from Responses to Vaccines

Autologous stem cell transplantation (ASCT) to treat autoimmune diseases (AID) is thought to reset immunological memory directed against autoantigens. This hypothesis can only be studied indirectly because the exact nature of the pathogenetic autoantigens is unknown in most AID. Therefore, 19 children with juvenile idiopathic arthritis (JIA) or systemic lupus erythematodes (SLE) and 10 adults with multiple sclerosis (MS) were vaccinated with the T-cell-dependent neoantigen rabies and the recall antigen tetanus toxoid after, respectively before, bone marrow harvest. Both vaccinations were repeated after ASCT. All except two of the responders mounted a primary antibody response to rabies after revaccination, and 44% of the responders mounted a primary antibody response to tetanus boost after ASCT. These data show that immunological memory to a neoantigen is lost in most patients with AID after immunoablative pretreatment; however, memory to a recall antigen boosted before bone marrow harvest is only lost in part of the patients. Disease progression was arrested in all patients with JIA/SLE except one, but only in a minority of MS patients. Clinical outcome on a per case basis was not associated with the profile of the immune response toward the vaccination antigens after ASCT.

Intratracheally Administered Pathogen-Associated Molecular Patterns Affect Antibody Responses of Poultry

Various potential immune-modulating microbially derived pathogen-associated molecular patterns (PAMP), or so called homotopes, are present in high concentrations in the environment of food animals. In previous studies, intravenously administered PAMP had variable effects on specific primary and secondary immune responses of poultry to systemically administered antigens. In the present study, we evaluated the effects of intratracheal (i.t.) challenge with the PAMP lipopolysaccharide, lipoteichoic acid (LTA), and Zymosan-A (containing 1,3 beta-glucan) on primary and secondary (total) antibody (Ab) responses and (isotype) IgM, IgG, and IgA responses to systemically administered human serum albumin (HuSA), and Ab titers to infectious bursal disease (Gumboro virus) and infectious bronchitis vaccines in layer hens at 9 and 22 wk of age. Birds were challenged via the trachea with PAMP for 5 consecutive days prior to primary and secondary immunization with HuSA. Intratracheally administered LTA and, to a minor extent, lipopolysaccharide significantly enhanced secondary total and IgG Ab responses to HuSA. 1,3 beta-Glucan did not significantly affect Ab responses to HuSA. All birds challenged with PAMP showed a decreased BW. Higher total Ab titers to infectious bursal disease and infectious bronchitis were found in birds challenged with LTA. The present results indicate that i.t. administered PAMP affect the humoral immune responsiveness of poultry, which may lead to an enhanced status of immune reactivity. Furthermore, our results suggest that the hygienic status of the environment influences BW (gain). The consequences of immune modulation by airborne PAMP or hygienic conditions in chicken husbandry for vaccine delivery and immune responsiveness of poultry are discussed.

Immunogenicity of Standard‐Titer Measles Vaccine in HIV‐1–Infected and Uninfected Zambian Children: An Observational Study

Achieving the level of population immunity required for measles elimination may be difficult in regions of high human immunodeficiency virus type 1 (HIV-1) prevalence, because HIV-1-infected children may be less likely to respond to or maintain protective antibody levels after vaccination. We conducted a prospective study of the immunogenicity of standard-titer measles vaccine administered at 9 months of age to HIV-1-infected and uninfected children in Lusaka, Zambia. From May 2000 to November 2002, 696 children aged 2-8 months were enrolled. Within 6 months of vaccination, 88% of 50 HIV-1-infected children developed antibody levels of >or=120 mIU/mL, compared with 94% of 98 HIV-seronegative children and 94% of 211 HIV-seropositive but uninfected children (P=.3). By 27 months after vaccination, however, only half of the 18 HIV-1-infected children who survived and returned for follow-up maintained measles antibody levels >or=120 mIU/mL, compared with 89% of 71 uninfected children (P=.001) and in contrast with 92% of 12 HIV-1-infected children revaccinated during a supplemental measles immunization activity. Although HIV-1-infected children showed good primary antibody responses to measles vaccine, their rapid waning of antibody suggests that measles vaccination campaigns may need to be repeated more frequently in areas of high HIV-1 prevalence.