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1.
We sought to determine whether palatine tonsils (PTs) harbor naturally acquired influenza-specific T cell immunity and whether routine parenteral immunization with influenza vaccine influences mucosal and systemic T cell reactivity. We demonstrate that tonsillar and peripheral blood mononuclear cells (PBMCs) proliferate strongly to influenza antigens, suggesting that naturally acquired immunity exists within both the mucosal and systemic compartments. Influenza vaccination induced significantly stronger T cell responses in both PTs and blood, in addition to increasing titers of anti-influenza antibodies in serum and saliva. More-rapid proliferative responses of PTs after vaccination were associated with a shift from a response involving both CD45RA+ and CD45RO+ T cells to an entirely CD45RO+-dependent response. Interestingly, the ratio of interferon- gamma to interleukin-5 was dramatically higher in cultures of PT T cells responding to influenza than in PBMCs. Our data indicate that parenteral influenza vaccination influences both mucosal and systemic naturally acquired T cell immunity.  相似文献   

2.
Although nasal vaccination has emerged as an interesting alternative to intramuscular or oral vaccination, knowledge is scarce about the immune responses after such immunization. In the present study, we inoculated purified Pertussis Toxin (PT) and Filamentous Haemagglutinin (FHA) with or without adjuvant (kayexalate), or Diphtheria acellular Pertussis Tetanus (DaPT) combined vaccine to mice intranasally three times every four weeks to investigate the references of the immunoresponses between nasal and intramuscular vaccination. The levels of pertussis specific serum IgG antibodies (Abs) and secretory IgA Abs in the nasal wash were measured by ELISA, and cytotoxic T cell activities were examined by proliferative response, and compared with the result from intramuscular inoculation. We also studied the efficacy of adjuvant in the nasal vaccination. The intramuscular inoculation of pertussis vaccine induced serum IgG antibodies and cellular immunity against PT and FHA, but did not induce local IgA antibodies. On the other hand, the nasal inoculation induced both serum and local antibody responses. Moreover, it also induced significant cellular immunity to pertussis antigen. In nasal vaccination, the inoculation with adjuvant was superior to inoculation without adjuvant for the induction of both humoral and cellular immunity.  相似文献   

3.
Secretory antibody following oral influenza immunization   总被引:4,自引:0,他引:4  
Secretory IgA antibody may be important in protection against respiratory viral infections, and the concept of a common mucosal immune system offers the theoretical basis for the convenient stimulation of this antibody. Therefore, the oral route was compared with intramuscular injection in a double-blind, placebo-controlled study in young healthy volunteers. A killed influenza vaccine, given in enteric-coated capsules (total of 98 ug hemagglutinin of A/Bangkok) led to significant salivary and nasal IgA antibody rises in a 4-week period. The preimmunization titers in secretions were inversely correlated with the antibody rise after immunization. The orally administered vaccine was associated with no more side effects than placebo, in contradistinction to reactions following the intramuscular route. The latter route also was without significant effect in regard to a stimulation of secretory antibodies. The observed simultaneous induction of antibodies in saliva and nasal secretions following oral administration of killed vaccine gives further evidence of a common mucosal immune system and its possible clinical use.  相似文献   

4.
The objective of this observational study is to determine characteristics as predictive factors for the humoral immune response to the influenza vaccine in patients with rheumatoid arthritis (RA). Fifty-seven RA patients who visited our department between 2011 and 2012 were recruited for the present study. The anti-influenza antibody titers of a trivalent influenza subunit vaccine (A/California/7/2009 (H1N1)-like strain (A/H1N1 strain), A/Victoria/210/2009 (H3N2)-like strain (A/H3N2 strain), and B/Brisbane/60/2008-like strain (B strain)) were measured at baseline and 4 weeks after the vaccination using the hemagglutination inhibition assay. Associations between the immune response to the influenza vaccine and clinical characteristics such as background, clinical parameters, and “having treatments or not” were examined to determine predictive factors for the immune response to the influenza vaccine. The titers of the three strains were significantly increased in all RA patients after the influenza vaccination. Concerning predictive factors of the immune response, no significant differences were observed in background (age and sex) or clinical parameters (peripheral lymphocyte count, C-reactive protein, erythrocyte sedimentation rate, rheumatoid factor, matrix metalloproteinase-3, and disease activity score-28). No significant differences were observed in the titers of anti-influenza antibodies between the treatment (methotrexate, prednisolone, salazosulfapyridine, or tacrolimus) and no-treatment groups. In contrast, there was a significant difference in A/H3N2 strain between the patients with biologics and without biologics. The only factor that affected anti-influenza antibody titers was “having biologics or not”; therefore, the immune response to the influenza vaccine may not be predicted from the viewpoints of background and clinical parameters.  相似文献   

5.
A Vero cell-derived whole-virus H5N1 influenza vaccine has been shown to induce neutralizing antibodies directed against the hemagglutinin (HA) protein of diverse H5N1 strains in animal studies and clinical trials. However, neuraminidase-inhibiting (NAi) antibodies can reduce viral spread and may be of particular importance in the event of an H5N1 pandemic, where immunity due to HA antibodies is likely absent in the general population. Here we demonstrate the effective induction of NAi antibody titers after H5N1 vaccination in humans. In contrast to the immune response directed toward HA, a single vaccine dose induced a strong NAi response that was not significantly boosted by a second dose, most probably due to priming by previous vaccination or infection with seasonal influenza viruses. After 2 immunizations, seroconversion rates based on antibody titers against HA and NA were similar, indicating the induction of equally strong immune responses against both proteins by this H5N1 vaccine.  相似文献   

6.
OBJECTIVE: To determine the efficacy of influenza virus vaccine in patients with systemic lupus erythematosus (SLE). METHODS: The study population comprised 24 patients with SLE who received the split-virion, inactivated vaccine containing 15 micro g hemagglutinin (HA)/dose of each of A/Beijing/262/95(H1N1), A/Sydney/05/97(H3N2), and B/Harbin/07/94. Hemagglutination inhibition (HI) antibodies were tested using the HI test according to a standard World Health Organization procedure. Immune response was defined as 4-fold or greater rise in HI antibodies 6 weeks after vaccination. Geometric mean titers (GMT) were calculated to assess the immunity of the whole group. RESULTS: All patients were women. Prior to vaccination, the percentage of SLE patients with protective levels of HI antibodies and the GMT of HI antibodies were similar to those of age matched healthy women. Six weeks after vaccination, 75% of the patients had immune response to at least one of the 3 antigens; 58.3% and 62.5% of the patients responded to A/Sydney/05/97(H3N2) and B/Harbin/07/94, respectively. However, only 37.5% of the patients responded to A/Beijing/262/95(H1N1). Six weeks after immunization, the SLE patients generated immune response against a mean number of 1.5 of the 3 influenza vaccines. There was a trend toward a lower immune response in patients with age > or = 50 years, prednisone dosage > or = 10 mg daily, and who used azathioprine. However, methotrexate therapy was not associated with decreased response. CONCLUSION: The immune response to influenza vaccine of patients with SLE is lower than that seen in adults in the general population, in particular among older patients and those treated with immunosuppressive therapy.  相似文献   

7.
The effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on the serological response at influenza vaccination was studied in 117 patients who had undergone stem cell transplantation (SCT). The vaccine response was evaluated as significant increases in levels of influenza hemagglutination-inhibition (HAI) antibodies and of IgG antibodies measured by enzyme-linked immunosorbent assay (ELISA). There was no difference in antibody response to either influenza A or B in 64 patients who received GM-CSF at vaccination, compared with the 53 who did not. In the subgroup of allogeneic SCT patients, HAI showed that the response rate to the influenza B vaccine was significantly higher in the treatment group (P<.05). ELISA showed that autologous SCT patients with breast cancer who received GM-CSF had a better response to influenza A (P<.05) and B (P<.01). At early vaccination, 4-12 months after stem cell transplantation, these responses were more pronounced. GM-CSF appears to improve the response to influenza vaccination in some groups of SCT patients, but only to a limited extent.  相似文献   

8.
This study investigated the effect of natural priming and age on serum IgG and IgA subclass responses after parenteral trivalent influenza vaccination. Sera from 18 young children and 8 adults were collected at various times after vaccination. An ELISA was performed to quantify the concentrations of antibody subclasses. The children were divided into primed and unprimed groups based on the presence of prevaccination serum antibodies. In both children and adults, IgG1 and IgA1 were the predominant IgG and IgA subclasses detected after vaccination. No IgG2 responses were detected in sera of unprimed children, and the proportion of the IgG2 response was lower in primed children than in adults. This suggests that the IgG2 immune response in young children is dependent on previous priming and may mature later than the other IgG subclasses after parenteral influenza vaccination.  相似文献   

9.
Rubella virus-specific IgM and IgA antibodies were quantitated by antibody capture immunoassay in adults after primary infection and after experimentally induced reinfection. Antibodies to rubella virus were also detected in fetuses whose mothers had rubella before week 18 of pregnancy. IgM and IgA concentrations in fetal blood were determined by radial immunodiffusion and enzyme immunoassay, respectively. In primary postnatal infection, IgM antibodies were consistently found until week 8 after onset of the disease, and after week 14 these antibodies were usually no longer detected. The time of disappearance of rubella virus-specific IgA varied with each individual. After vaccination of previously immune volunteers, no change was noted in level of IgA antibody, and no IgM antibody was detected. In infected fetuses, total IgM and IgA concentrations rose significantly, and rubella virus-specific IgM and IgA antibodies were detected as early as week 22 of pregnancy.  相似文献   

10.
Background and Objective In this study we investigated the levels of cytokines and chemokines produced locally and systemically after influenza vaccination of patients undergoing tonsillectomy. Methods Blood and saliva were collected prior to, and 1 or 2 weeks after vaccination at the time of the tonsillectomy. The cytokine and chemokine concentrations were determined in both unstimulated (whole blood, serum and saliva) and in vitro influenza stimulated peripheral blood mononuclear cell (PBMC) and tonsillar lymphocyte (TMC) cultures. Results We found that influenza vaccination elicited protective levels of serum haemagglutination inhibition antibodies and a significant local antibody response in the saliva. No significant differences were observed in the cytokine or chemokine levels 1 or 2 weeks post‐vaccination in either the serum or saliva. Similarly, no significant differences were found in the gene expression levels in PBMC after vaccination, but interleukin (IL)‐2, IL‐4, γ‐interferon and transforming growth factor‐β were slightly elevated at 1 week post‐vaccination but decreased by 2 weeks post‐vaccination. In contrast, increased concentrations of a mixture of type 1, type 2 and inflammatory cytokines were produced 1 and 2 weeks after influenza vaccination by in vitro‐stimulated PBMC and TMC. Conclusion We show that cytokine responses can be measured after influenza vaccination in in vitro‐stimulated lymphocytes but not directly in the blood or saliva. These results will provide a useful baseline that can be used for comparison of the immune response in human volunteers involved in clinical trials of novel influenza vaccines.  相似文献   

11.
AIM: To prepare poly (D,L-lactide)-polyethylene glycol copolymer (PELA) microspheres loaded H.pylori lysates or Cystografin and observe their targeting in gastrointestinal mucous membrane or analyze the mucosal immune responses by oral administration. METHODS: PELA microspheres loaded H.pylori lysates or Cystografin were prepared by double emulsion evaporation method. Their distribution in gastrointestinal mucous membrane was observed by CT. Balb/c mice orally immunized in mucosal immune responses, whose antibody production in salivary and gut washing and antibody secreting cells in Peyer's patches (PP) were estimated by ELISA and ELISPOT, respectively. The microspheres physical properties, such as particle size, protein level and morphology were investigated. RESULTS: All prepared microspheres were found to have a smooth surface morphology from 3.20-4.05 microm in diameter and high encapsulation efficiency from 74.9-82.2 %. No significant correlation in their physical properties was shown, depending on their molecular weight at the similar composition ratio. Immunization with all types of PELA-Hp microspheres elevated the saliva sIgA level at week 3 by approximately 3-4 times that with soluble antigen, which was greatly enhanced after boosting. At one week after last immunization with all types of PELA-Hp microspheres (week 8), the specific sIgA-ASCs, IgG-ASCs and sIgA in salivary rose obviously. In intestinal Peyer's patches, the specific sIgA-ASCs were 5.92-6.98X10(4)/ml cell and IgG-ASCs were 3.47-4.02X10(4)/ml cell, about 5-9 times higher than those with soluble antigen (P<0.01). ASCs in intestine were more than those in stomach and the majority of the ASCs were sIgA-ASCs. The sIgA in gut washing fluid was 1.62-1.85 OD, about 3-6 times tthat of those with soluble antigen. There were significant differences of the ASCs and sIgA in gut washing fluid as compared with those of PBS and MS-0 (P<0.05). There appeared to be good correlation between sIgA level in gut washing fluid and sIgA-ASCs in intestinal Peyer's patches. CONCLUSION: PELA microspheres may be used as vehicle to delivery antigen and adjuvant in designing oral vaccination.  相似文献   

12.
BACKGROUND: Influenza virus and respiratory syncytial virus (RSV) are among the most common viruses causing infections of the lower respiratory tract in young children. Although there are important differences in the immunopathogenesis of these 2 viral pathogens, little is known about how they affect antigen-presenting cells in children with acute infections. METHODS: To characterize the immune cells that are mobilized to the respiratory tract by influenza virus and RSV, we analyzed nasal wash and blood samples obtained from children hospitalized with acute respiratory infections. RESULTS: Influenza virus and RSV mobilize immune cells, including myeloid dendritic cells (mDCs) and plasmacytoid dendritic cells (pDCs), to the nasal mucosa. Patients with influenza virus infection had greater numbers of mDCs, pDCs, and monocytes in nasal wash samples than did patients with RSV infection. The frequencies of respiratory tract and blood T cell subsets were not affected by infection with influenza virus or RSV. Monocyte chemoattractant protein-1 concentrations in nasal wash samples were significantly increased in patients with influenza virus infection but not in those with RSV infection. RANTES (regulated on activation, normally T cell expressed and secreted) concentrations were increased only in the blood of patients with influenza virus infection. CONCLUSIONS: Infection with influenza virus or RSV mobilizes antigen-presenting cells to the respiratory tract. The differences in antigen-presenting cell numbers and cytokine concentrations suggest that there are distinctive, early immune responses to these 2 viruses.  相似文献   

13.
We investigated immune responses in 63 mentally retarded patients each given a low-dose (4 micrograms) intradermally of plasma-derived hepatitis B vaccine made in Japan and which was repeated after 1 and 6 months. Two doses of the vaccine induced antibodies in 85.5% these patients. A further dose 6 months later induced antibodies in 93.5% of the recipients and markedly increased the proportion of recipients with acceptable or high concentrations of antibody. The numbers of acceptable and high responders decreased slightly during a period of 12 months. The rate of acquiring antibody was significantly higher in the males. No significant differences in antibody response with regard to age and type of disease were observed. One patient with Down's syndrome, who acquired a low concentration of antibody after vaccination, was infected with hepatitis B virus. Supplementary vaccination may be necessary for poor responders in order to obtain protection. Side-effects resulting from the vaccination were not severe in any patients. These results suggest that low-dose, intradermal hepatitis B vaccination is safe and effective.  相似文献   

14.
Aim: To investigate the distribution of hemagglutination inhibition (HI) titers before and after influenza vaccination and to examine the relationship between physical and nutritional factors and the change in HI titer after influenza vaccination in the elderly. Methods: Pre‐post‐vaccination HI titers were determined from 203 individuals aged 65 years or older residing in a nursing home. For the assessment of physical and nutritional status, information was retrieved from care records. Results: The immune response to vaccination was assessed as good in 122 subjects based on a fourfold rise or more in HI titer after vaccination for at least one of three vaccine strains. In univariate logistic regression analysis with poor versus good immune response as the dependent variable, factors found to be significantly associated with a poor immune response were disability, a combination of body mass index less than 18.5 and bodyweight loss in 6 months or 5% or more, mid‐upper‐arm circumference of less than 80%, arm muscle circumference of less than 80% and total protein of less than 6.5 g/dL. Physical and nutritional indicators might be useful in identifying individuals who are unlikely to have a good immune response to influenza vaccination. In a multivariate analysis, the association remained significant for a low level of activities of daily living and a combination of body mass index of less than 18.5 and bodyweight loss in 6 months of 5% or more. Conclusion: Elderly individuals with poor physical and nutritional status tended to respond poorly to influenza vaccination. A low level of activities of daily living and a combination of being underweight and having had recent bodyweight loss are good indicators of a poor immune response. Geriatr Gerontol Int 2011; 11: 63–68.  相似文献   

15.
Lethally irradiated Balb/c mice reconstituted with syngeneic T cell-depleted or syngeneic untreated bone marrow (BM) were able to produce equal levels of hemagglutination inhibition (HI) antibodies at 4 weeks after bone marrow transplantation (BMT) in response to nasal infection with A/PR8 influenza virus given 1 week after BMT. Likewise, no differences in mortality rates could be observed following influenza virus infection 1 day after BMT. Antibody production was detected in 10-20% of BMT recipients. All animals responded to a secondary infection given 2 months later by production of secondary IgG-type HI antibodies. Mice reconstituted with BM enriched with spleen cells obtained from immune donors showed an improved survival rate as compared with recipients of na?ve BM, immune BM or T-depleted BM obtained from immune mice. Our results indicate that T cell depletion by itself does not increase susceptibility of syngeneic BMT recipients to virus infection. However, immune spleen cells may play a significant role in conveying protection against influenza virus infections. Although recipients of both immune and na?ve intact BM may mount better anti-influenza titers as compared with T-lymphocyte-depleted BMT recipients, it appears that the proportion of immune donor T cells in the marrow inoculum is insufficient for protection against influenza virus infection. Generation of memory cells to influenza viral antigens in the post-BMT period is not impaired in recipients of T-depleted marrow grafts, suggesting that memory cell precursors are unaffected by the T cell depletion procedure, or else that they were regenerated during the immediate post-BMT period from Thy 1.2-negative precursors.  相似文献   

16.
BACKGROUND: Yearly influenza vaccination, although recommended for human immunodeficiency virus (HIV)-infected individuals, has not received thorough evaluation in the era of antiretroviral therapy. We assessed the impact of HIV disease on B cell responses to influenza vaccination. METHODS: Sixty-four HIV-infected and 17 HIV-negative individuals received the 2003-2004 trivalent inactivated influenza vaccine. Frequencies of influenza-specific antibody-secreting cells (ASCs) were measured by enzyme-linked immunospot (ELISPOT) assay, and antibody responses were measured by hemagglutination-inhibition (HI) assay. Memory responses to influenza were measured by ELISPOT assay after polyclonal activation of B cells in vitro. RESULTS: Prevaccination HI titers were significantly higher in HIV-negative than in HIV-infected individuals. Peak HI titers and influenza-specific ASC frequencies were directly correlated with CD4+ T cell counts in HIV-infected individuals. Influenza-specific memory B cell responses were significantly lower in HIV-infected than in HIV-negative individuals and were directly correlated with CD4+ T cell counts. CONCLUSIONS: HIV infection is associated with a weak antibody response to influenza vaccination that is compounded by a poor memory B cell response. CD4+ T cell count is a critical determinant of responsiveness to influenza vaccination, and the contribution of plasma HIV RNA level is suggestive and warrants further investigation.  相似文献   

17.
BACKGROUND: Immunization prepares the body for a reencounter with the microbe. Information on the targeting of immune effector cells during secondary immune response--that is, lymphocyte homing--is scarce. In the present study, the homing potentials of lymphocytes are examined after antigen reencounter at mucosal versus nonmucosal sites. METHODS: Orally or parenterally immunized volunteers were reimmunized orally or parenterally with Salmonella typhi Ty21a, and the expression of the gut homing receptor (HR), alpha(4)beta(7), and of the peripheral lymph node HR, L-selectin, was investigated in circulating antigen-specific antibody-secreting cells (ASCs). Lymphocytes were sorted by HR expression and examined for antibody production, by use of an enzyme-linked immunospot assay. RESULTS: After oral reimmunization, 90% of ASCs were alpha(4)beta(7) positive and 88% were L-selectin positive, an expression profile that differed significantly from that found after oral primary immunization. After parenteral reimmunization, 45% of ASCs were alpha(4)beta(7) positive and 79% were L-selectin positive, similar to the results after parenteral primary immunization. The route of priming had no effect on HR patterns in either case. CONCLUSIONS: Homing potentials of lymphocytes depend on the site of antigen reencounter. Whereas the HR profile after parenteral reimmunization resembles that after primary immunization, the profile after oral reimmunization is uniquely characterized by high expression of both HRs, suggesting gut-localized memory and effective homing ability to both the mucosal and systemic immune system. These data may prove valuable in the search for the most effective immunization route in humans.  相似文献   

18.
The cytotoxic T-cell and humoral immune response to a commercially available influenza A-H1N1 subunit vaccine in 14 patients with type 1 diabetes mellitus was compared with the response in 13 healthy volunteers. Cytotoxic T-cell response to vaccination was poor in both patients and controls. At a calculated 50: 1 effector-target cell ratio, however, significantly more controls than patients showed an increase of over 5% cytotoxic T-cell mediated lysis after vaccination (P less than 0.05). In patients the cytotoxic T-cell response decreased with higher percentages of glycosylated haemoglobin (regression coefficient not equal to 0 with P less than 0.05). No significant difference was found between diabetic patients and control subjects with respect to antibody response after vaccination. Implications for vaccination strategy are discussed.  相似文献   

19.
Despite considerable evidence that cell activation enhances human immunodeficiency virus-type 1 (HIV-1) replication in vitro, there is very little data on the role of immune activation on in vivo HIV-1 replication. In this study, we examined the effect of influenza vaccination on HIV-1 replication in the peripheral blood of 20 study subjects, and in 14 control subjects who did not receive influenza vaccination. Blood was obtained from each subject on three occasions during the month before vaccination and again on three occasions during the following month. Over the study period, there was little change in levels of proviral DNA in peripheral blood mononuclear cells (PBMCs). However, peak PBMC viral RNA levels after influenza vaccination were significantly increased over the mean of prevaccination values. This change was not observed to the same extent in unvaccinated controls. Therefore, this is the first report showing that HIV-1 replication can increase in temporal association with influenza vaccination. Our results suggest that continued immunologic (antigenic) stimulation may result in increased virus load in vivo. To address the appropriateness of influenza vaccination in HIV-infected patients, expanded studies will be required to examine specific and generalized immune responses to vaccination, and differences in patient response based on disease stage.  相似文献   

20.
Pigs single inoculated with Ascaris suum eggs expel the majority of larvae between days 14 and 21 post inoculation (p.i.), but the role of the immune system in expulsion is unclear. To investigate the dynamics of immune responses before, during and after the expulsion of A. suum larvae, pigs inoculated with 10 000 A. suum eggs were sequentially necropsied. Ascaris suum gradually moved distally from days 10-14 p.i. and only a few larvae were left by day 21 p.i. Pronounced increases in mucosal A. suum-specific IgA antibody secreting cells (ASCs) were already found by day 10 p.i. especially in the proximal jejunum, while only small increases in parasite-specific IgM ASCs were observed by day 21 p.i. in both proximal and distal jejunum. No mucosal IgG ASC responses could be detected. Increases in systemic A. suum-specific IgG1, IgM and to a lesser extent IgA antibodies were observed, while IgG2 remained almost unchanged. The levels of eosinophils and mast cells in the small intestinal mucosa did not change throughout infection. The results demonstrate that both systemic and mucosal A. suum-specific effector mechanisms are strongly stimulated in A. suum single infections and indicate that mucosal IgA may be an important mediator in the expulsion of A. suum.  相似文献   

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