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1.
Humoral immune response to HSV-1 and HSV-2 viral proteins in patients with primary genital herpes 总被引:13,自引:0,他引:13
The humoral immune response to HSV-1 and HSV-2 proteins was examined in patients with primary first-episode genital herpes. Ten patients had culture-proven HSV-1 infections, 37 had HSV-2 infections, and all were seronegative to HSV proteins before developing their infections. Development of serum antibodies to individual HSV proteins and glycoproteins was determined by immunoprecipitation of radiolabeled HSV-1- and HSV-2-infected cell proteins and subsequent gel electrophoresis. In HSV-1 patients, a sequential development of antibodies to HSV-1 proteins was observed with early appearance of antibodies to the nucleocapsid protein p148 and to glycoproteins gB and gC. Seroconversion to gD and to a polypeptide of 88,000 molecular weight (p88) occurred next, and, finally, seroconversion to gE and to a nonglycosylated 66,000 dalton protein p66. In HSV-2 patients, antibodies to HSV-2 proteins p148, gB, and p88 appeared within 1 week of onset of symptoms. Seroconversion to p66, gD, and to a complex of glycoproteins gC and gE ("g80") occurred later, at a mean time of approximately 3 weeks. Seroconversion to HSV-1 gB, p88, and p66 occurred significantly later than seroconversion to the homologous counterparts. Seroconversion within 21 days of onset to HSV-2 gD, g80, and p66 was associated with a longer time to the first recurrence in HSV-2 patients, suggesting a possible role of these antibodies, alone or in combination, in the maintenance of HSV-2 latency in humans. 相似文献
2.
Yi-Chun Lai Kuen-Cheh Yang Szu-Min Hsieh Chien-An Yao Long-Teng Lee Kuo-Chin Huang 《Clinical and Vaccine Immunology : CVI》2012,19(3):429-435
After WHO declared H1N1 pandemic, global vaccination was carried out immediately after much research. However, the data on long-term immunogenicity were lacking. We aimed to investigate the long-term immunogenicity of different H1N1 vaccine dosage groups 24 weeks after vaccination by a randomized clinical trial. A total of 218 participants were stratified into adult (≤60 years old) and elderly (>60 years old) groups. The adults were randomized in a 1:1:1 ratio. The first group received a single dose of vaccine with 15 μg hemagglutination antigen (HA). The other two groups received two doses with 15 μg or 30 μg HA triweekly. The elderly were randomized 1:1 for two doses of 15 or 30 μg HA. We evaluated serologic responses at prevaccination and weeks 3, 6, and 24. We also examined possible associated factors of immunogenicity by multivariate logistic regression analyses. At week 24, seroprotection (anti-HA antibody level ≥ 1:40) remained at 76.8% and 46.2% in the adult and elderly groups, respectively. The adult group had a higher seroprotection rate (odds ratio of 2.98, 95% confidence interval [CI]: 1.21 to 7.36) than the elderly group. There was no statistical difference in seroprotection and seroconversion rates between different adult and elderly dosage groups. Lower immunogenicity in the elderly than in the adults 24 weeks after the vaccination was observed. However, there was no statistically significant difference among different dose groups. Therefore, we suggest only a single vaccination dose of 15 μg HA for adults and two doses of 15 μg HA for the elderly in the future. 相似文献
3.
With the recent pandemic of influenza A (H1N1) and vaccine shortages, there has been considerable interest in developing influenza vaccines with reduced doses, allowing for increased production capacity. Here we report a prospective, randomized, double-blind, single-center clinical trial of a reduced-dose whole-virion inactivated, adjuvanted influenza vaccine in adult and elderly volunteers. A total of 234 subjects, including 120 adults (18 to 60 years of age) and 114 elderly subjects (>60 years of age) were enrolled to receive either 6 μg or the conventional 15-μg dose of seasonal trivalent influenza vaccines. The subjects were followed for safety analysis, and serum samples were obtained to assess immunogenicity by hemagglutination inhibition testing. The subjects developed antibody responses against the seasonal influenza A virus H1N1 and H3N2 strains, as well as the seasonal influenza B virus included in the vaccines. Single doses of 6 μg fulfilled licensing criteria for seasonal influenza vaccines. No significant differences in rates of seroconversion or seroprotection or in geometric mean titers were found between the two dosage levels. All adverse events were rare, mild, and transient. We found that the present reduced-dose vaccine is safe and immunogenic in healthy adult and elderly subjects and triggers immune responses that comply with licensing criteria. 相似文献
4.
Ge Liu Langzhou Song David W. C. Beasley Robert Putnak Jason Parent John Misczak Hong Li Lucia Reiserova Xiangyu Liu Haijun Tian Wenzhe Liu Darlene Labonte Lihua Duan Youngsun Kim Linda Travalent Devin Wigington Bruce Weaver Lynda Tussey 《Clinical and Vaccine Immunology : CVI》2015,22(5):516-525
The envelope (E) protein of flaviviruses includes three domains, EI, EII, and EIII, and is the major protective antigen. Because EIII is rich in type-specific and subcomplex-specific neutralizing epitopes and is easy to express, it is particularly attractive as a recombinant vaccine antigen. VaxInnate has developed a vaccine platform that genetically links vaccine antigens to bacterial flagellin, a Toll-like receptor 5 ligand. Here we report that tetravalent dengue vaccines (TDVs) consisting of four constructs, each containing two copies of EIII fused to flagellin (R3.2x format), elicited robust and long-lived neutralizing antibodies (geometric mean titers of 200 to 3,000), as measured with a 50% focus reduction neutralization test (FRNT50). In an immunogenicity study, rhesus macaques (n = 2) immunized subcutaneously with 10 μg or 90 μg of TDV three or four times, at 4- to 6-week intervals, developed neutralizing antibodies to four dengue virus (DENV) serotypes (mean post-dose 3 FRNT50 titers of 102 to 601). In an efficacy study, rhesus macaques (n = 4) were immunized intramuscularly with 16 μg or 48 μg of TDV or a placebo control three times, at 1-month intervals. The animals that received 48-μg doses of TDV developed neutralizing antibodies against the four serotypes (geometric mean titers of 49 to 258) and exhibited reduced viremia after DENV-2 challenge, with a group mean viremia duration of 1.25 days and 2 of 4 animals being completely protected, compared to the placebo-treated animals, which all developed viremia, with a mean duration of 4 days. In conclusion, flagellin-EIII fusion vaccines are immunogenic and partially protective in a nonhuman primate model. 相似文献
5.
Pierre Alex Crisinel Klara Maria Posfay-Barbe Christoph Aebi Jean-Jacques Cheseaux Christian Kahlert Christoph Rudin David Nadal Claire-Anne Siegrist 《Clinical and Vaccine Immunology : CVI》2012,19(11):1751-1757
Vaccination in HIV-infected children is often less effective than in healthy children. The goal of this study was to assess vaccine responses to hepatitis A virus (HAV) in HIV-infected children. Children of the Swiss Mother and Child HIV Cohort Study (MoCHiV) were enrolled prospectively. Recommendations for initial, catch-up, and additional HAV immunizations were based upon baseline antibody concentrations and vaccine history. HAV IgG was assessed by enzyme-linked immunosorbent assay (ELISA) with a protective cutoff value defined as ≥10 mIU/ml. Eighty-seven patients were included (median age, 11 years; range, 3.4 to 21.2 years). Forty-two patients were seropositive (48.3%) for HAV. Among 45 (51.7%) seronegative patients, 36 had not received any HAV vaccine dose and were considered naïve. Vaccine responses were assessed after the first dose in 29/35 naïve patients and after the second dose in 33/39 children (25 initially naïve patients, 4 seronegative patients, and 4 seropositive patients that had already received 1 dose of vaccine). Seroconversion was 86% after 1 dose and 97% after 2 doses, with a geometric mean concentration of 962 mIU/ml after the second dose. A baseline CD4+ T cell count below 750 cells/μl significantly reduced the post-2nd-dose response (P = 0.005). Despite a high rate of seroconversion, patients with CD4+ T cell counts of <750/μl had lower anti-HAV antibody concentrations. This may translate into a shorter protection time. Hence, monitoring humoral immunity may be necessary to provide supplementary doses as needed. 相似文献
6.
我们以前曾报道,表达单纯疱疹病毒Ⅱ型糖蛋白D(HSV-2gD)的重组痘苗病毒(实验疫苗株)能保护被免疫小鼠抵抗致死量HSV-2病毒的攻击。在此工作基础上,严格按人用疫苗研究要求的实验条件,成功地建立了表达HSV-2gD的重组痘苗病毒活疫苗株。首先将经聚合酶链反应(PCR)修饰的HSV-2gD基因插入痘苗表达质粒pJSB1175,置于痘苗病毒P75K早/晚期启动子控制下。将此重组质粒用Lipofectin方法转染已受野型TK+痘苗病毒天坛761株感染的人胚肺二倍体细胞。经同位素探针(32P-HSV-2gD)原位杂交法和3轮蚀斑纯化,筛选出基因组内整合有HSV-2gD基因的重组痘苗病毒。斑点和Southern杂交证实,HSV-2gD基因已插入痘苗病毒基因组内预期的TK区段,间接免疫荧光检测显示,重组病毒感染细胞后能有效地表达HSV-2gD蛋白。 相似文献
7.
表达单纯疱疹病毒Ⅱ型糖蛋白D的重组痘苗病毒活疫苗… 总被引:1,自引:0,他引:1
我们以前曾报道,表达单纯疱疹病毒Ⅱ型糖蛋白的重组痘苗病毒能保护被免疫小鼠抵抗致死量HSV-2病毒的攻击。在此工作基础上,严格按人用疫苗研究要求的实验条件,成功地建立了表达HSV-2gD的重组痘苗病毒活疫苗株,首先将经聚合酶链反应修饰的HSV-2gD基因插入痘苗表达质粒pJSB1175,置于痘苗病毒P7.5K早/晚期启动子控制下,将同位重组质粒用Lipofectin方法转染已受野型TK^+痘苗病毒天 相似文献
8.
目的:研究串联重组核酸疫苗pc(pcDNA3.1)-S(HBsAg)-P6-IL18和pc(pcDNA3.1)-S(HBsAg)-NP6-IL18对机体的免疫效果,P6是我们前期采用噬菌体展示技术筛选出的HSV-2gD的模拟抗原表位,NP6为与HSV-2gD模拟抗原表位P6最相似的天然抗原表位序列。方法:分别将空质粒pcDNA3.1(阴性对照组)和构建的真核表达质粒pc-S-P6-IL18和pc-S-NP6-IL18肌内注射免疫接种BALB/c小鼠3次,每次间隔2周。末次免疫后2周眼眶静脉采血,ELISA法检测小鼠血清特异性抗体滴度、IFN-γ及IL-18含量;末次免疫后一月,处死小鼠,无菌分离脾脏,用刀豆蛋白A刺激淋巴细胞,采用MTT法测定脾淋巴细胞增殖率。结果:重组核酸疫苗pc-S-P6-IL18和pc-S-NP6-IL18免疫小鼠后可刺激血清特异性抗体(抗HBsAg抗体和抗HSV-2gD模拟表位抗体)的产生,与阴性对照组相比可诱导分泌较高水平的IFN-γ和IL-18,可促进小鼠脾淋巴细胞的增殖。结论:重组核酸疫苗pc-S-P6-IL18和pc-S-NP6-IL18能诱导较强的细胞免疫和体液免疫,可用于今后预防HBV和HSV-2感染的研究。 相似文献
9.
G. J. Gorse D. H. Schwartz B. S. Graham T. J. Matthews D. M. Stablein S. E. Frey R. B. Belshe M. L. Clements P. F. Wright M. Eibl P. E. Fast 《Clinical and experimental immunology》1994,98(2):178-184
The purpose of this randomized, double-blind study was to test the safety and immunogenicity of an HIV-1LAI recombinant gp160 (rgp160) vaccine in healthy, uninfected volunteers using accelerated dosing schedules. Thirty volunteers were randomly assigned to receive 50-μg doses of rgp160 in one of two immunization schedules. Group 1 received rgp160 at times 0, 1, 2 and 5 months; and group 2 received rgp160 at times 0, 1, 2, 3 and 4 months. The vaccine was safe and stimulated high levels of HIV-1 envelope-specific binding antibody and T cell memory. There was a trend (P < 0.10) suggesting neutralizing antibodies were better induced by the regimen incorporating a rest period before the final immunization in group 1 volunteers. Both accelerated immunization schedules induced immune responses at levels similar to or better than those achieved by four rgp160 vaccine injections given over 12-18 months in other studies. 相似文献
10.
Low-dose priming before vaccination with the phase I chloroform-methanol residue vaccine against Q fever enhances humoral and cellular immune responses to Coxiella burnetii
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Although the phase I Coxiella burnetii cellular vaccine is completely efficacious in humans, adverse local and systemic reactions may develop if immune individuals are inadvertently vaccinated. The phase I chloroform-methanol residue (CMRI) vaccine was developed as a potentially safer alternative. Human volunteers with no evidence of previous exposure to C. burnetii received a subcutaneous vaccination with the CMRI vaccine in phase I studies under protocol IND 3516 to evaluate the safety and immunogenicity of the vaccine. This clinical trial tested escalating doses of the CMRI vaccine, ranging from 0.3 to 60 μg, followed by a booster dose of 30 μg, in a placebo-controlled study. Although priming doses of the CMRI vaccine did not induce a specific antibody detectable by enzyme-linked immunosorbent assay, booster vaccination stimulated the production of significant levels of anti-C. burnetii antibody. Peripheral blood cells (PBCs) of vaccinees responded to C. burnetii cellular antigen in vitro in a vaccine dose-dependent manner. After the booster dose, PBCs were activated by recall antigen in vitro, regardless of the priming dose. These findings suggest that vaccination with the CMRI vaccine can effectively prime the immune system to mount significant anamnestic responses after infection. 相似文献
11.
Abylay R. Sansyzbay Marianna K. Erofeeva Berik M. Khairullin Nurlan T. Sandybayev Zhailaubay K. Kydyrbayev Seidigapbar M. Mamadaliyev Markhabat M. Kassenov Maria V. Sergeeva Julia R. Romanova Vera Z. Krivitskaya Oleg I. Kiselev Marina A. Stukova 《Clinical and Vaccine Immunology : CVI》2013,20(8):1314-1319
In this study, we assessed in humans the immunogenicity and safety of one dose (7.5 or 15 μg of hemagglutinin [HA]) of a whole-virion inactivated prepandemic influenza vaccine adjuvanted with aluminum hydroxide. The vaccine strain was made by reverse genetics from the highly pathogenic avian A/Chicken/Astana/6/05 (H5N1) clade 2.2 strain isolated from a dead bird in Kazakhstan. The humoral immune response was evaluated after a single vaccination by hemagglutination inhibition (HI) and microneutralization (MN) assays. The vaccine was safe and immunogenic, inducing seroconversion in 55% of the evaluated patients, with a geometric mean titer (GMT) of 17.1 and a geometric mean increase (GMI) of 3.42 after a dose of 7.5 μg in the HI test against the vaccine strain. The rate of seroconversion increased up to 70% when the dose of 15 μg was used. The percentages of individuals achieving anti-HA titers of ≥1:40 were 52.5% and 57.5% for the 7.5- and 15-μg dose groups, respectively. Similar results were obtained when antibodies were analyzed in an MN test. Substantial cross-neutralization titers (seroconversion in 35% and 52.5% of subjects in the two dose groups, respectively) were detected against heterologous clade 1 strain NIBRG14 (H5N1). Thus, one dose of this whole-virion prepandemic vaccine adjuvanted with aluminum has the potential to be effective against H5N1 viruses of different clades. 相似文献
12.
Mechanism of induction of immunological tolerance: VI. Tolerance induction following thoracic duct drainage or treatment with anti-lymphocyte serum* 总被引:3,自引:0,他引:3
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G. R. Shellam 《Immunology》1969,17(2):267-280
Adult Wistar rats were injected with flagellin from Salmonella adelaide three times weekly for different periods of time. With the range of doses 100 fg to 100 μg (fg, femtograms), varying levels of immune responsiveness were demonstrable following challenge, but not one of the doses induced complete immunological tolerance, although a reduced antibody response was elicited in rats which received injections of 100 μg of flagellin.
In contrast to this finding, complete tolerance could be demonstrated following challenge if rats, previously drained of lymph and lymphocytes from the thoracic duct for 5 days, were injected with either 100 μg of flagellin three times weekly or with 1 μg/g body weight/day for 6 weeks. Similarly, anti-lymphocyte serum treatment prior to the injection of antigen resulted in partial tolerance in adult rats and nearly complete tolerance in adult C57BL/Brad mice. The primary response to flagellin of C57BL mice was abrogated if ALS was administered prior to but not after the injection of antigen. The implications of these findings are discussed.
相似文献13.
Summary. Antiviral effects of a DNA vaccine against herpes simplex virus 1 (HSV-1) glycoprotein D (gD) were evaluated in eight week-old
female BALB/c mice. The nuclease-insensitive construct (gD-ASOR) consisted of an HSV-1 gD encoding plasmid coupled to asialo
orosomucoid (ASOR), targeting it to cells bearing ASOR receptors. Mice were immunized on day 0 and 7 with 10 μg doses of gD-ASOR
or control substances. Fourteen days later, mice were infected by the corneal route with 105 pfu or 106 pfu HSV-1, strain 17syn+. Immunized mice showed a significant decrease in ocular disease severity over a 21-day observation
period following infection compared to sham-immunized mice. Acute replication kinetic assays demonstrated a 100-fold decrease
in viral titers on day 6 in trigeminal ganglia from immunized BALB/c mice compared to sham-immunized mice. Immunized mice
showed a significant increase in numbers of CD4+T cells infiltrating the trigeminal ganglia at day 6 post infection compared to sham-immunized mice. Significant differences
were not seen in latent viral reservoir between immunized and unimmunized mouse groups. Immunization with gD-ASOR decreased
the severity of acute ocular HSV-1 infection, induced a CD4+ T cell response, decreased the viral load in the trigeminal ganglia, but did not diminish viral latency.
Received December 17, 2001; accepted April 5, 2002 Published online July 10, 2002 相似文献
14.
Nina Wressnigg P. Noel Barrett Eva-Maria P?llabauer Maria O'Rourke Daniel Portsmouth Michael G. Schwendinger Brian A. Crowe Ian Livey Thomas Dvorak Bernhard Schmitt Markus Zeitlinger Herwig Kollaritsch Meral Esen Peter G. Kremsner Tomas Jelinek Roland Aschoff Roland Weisser Ingomar F. K. Naudts Gerald Aichinger 《Clinical and Vaccine Immunology : CVI》2014,21(11):1490-1499
Lyme borreliosis (LB) patients who recover, as well as previously infected asymptomatic individuals, remain vulnerable to reinfection with Borrelia burgdorferi
sensu lato. There is limited information available about the use of OspA vaccines in this population. In this study, a randomized double-blind phase I/II trial was performed to investigate the safety and immunogenicity of a novel multivalent OspA vaccine in healthy adults who were either seronegative or seropositive for previous B. burgdorferi sensu lato infection. The participants received three monthly priming immunizations with either 30 μg or 60 μg alum-adjuvanted OspA antigen and a booster vaccination either 6 months or 9 to 12 months after the first immunization. The antibody responses to the six OspA serotypes included in the vaccine were evaluated. Adverse events were predominantly mild and transient and were similar in the seronegative and seropositive populations. Substantial enzyme-linked immunosorbent assay (ELISA) and surface-binding antibody responses against all six OspA antigens were induced after the primary immunization schedule in both populations, and they were substantially increased with both booster schedules. The antibody responses induced by the two doses were similar in the seronegative population, but there was a significant dose response in the seropositive population. These data indicate that the novel multivalent OspA vaccine is well tolerated and immunogenic in individuals previously infected with B. burgdorferi sensu lato. (This study is registered at ClinicalTrials.gov under registration no. .) NCT01504347相似文献
15.
Functional Antibody Activity Elicited by Fractional Doses of Haemophilus influenzae Type b Conjugate Vaccine (Polyribosylribitol Phosphate–Tetanus Toxoid Conjugate)
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Sandra Romero-Steiner Josefina Fernandez Christel Biltoft Melissa E. Wohl Jacqueline Sanchez Jesus Feris Sharon Balter Orin S. Levine George M. Carlone 《Clinical and Vaccine Immunology : CVI》2001,8(6):1115-1119
We evaluated the functional activities of antibodies, serum bactericidal activity (SBA), and immunoglobulin G (IgG) antibody avidity indices, using sodium thiocyanate (NaSCN) elution, elicited after vaccination with fractional doses of the Haemophilus influenzae type b conjugate (polyribosylribitol phosphate [PRP] conjugated to tetanus toxoid [PRP-T]) vaccine. A cohort of 600 infants from the Dominican Republic were randomized to receive one of three regimens of the PRP-T vaccine at ages 2, 4, and 6 months: full doses (10 μg of PRP antigen), one-half doses (5.0 μg), and one-third doses (3.3 μg) (J. Fernandez et al., Am. J. Trop. Med. Hyg. 62:485–490, 2000). Sixty serum samples, collected at age 7 months, with ≥2.0 μg of anti-PRP IgG per ml were randomly selected for avidity determinations. Geometric mean IgG concentrations were 13, 14, and 17 μg/ml for infants who received the full-dose (n = 19), one-half-dose (n = 19), and one-third-dose (n = 22) regimens, respectively. SBA geometric mean titers (1/dilution) were 85.0, 82.0, and 76.1 in sera from infants receiving the full-, one-half-, and one-third-dose regimens, respectively. Avidity indices (mean ± standard error weighted average of NaSCN molar concentration × serum dilution factor) were 71.9 ± 9.4, 123.6 ± 26.8, and 150.9 ± 24.9 for the full-, one-half-, and one-third-dose regimens, respectively. Upon comparison, the only significant difference (P = 0.024) found was a greater avidity index for sera from infants receiving the one-third-dose regimen than for sera from infants receiving the the full-dose regimen. We conclude that fractional doses elicit similar functional antibody activities in infants with ≥2 μg of anti-PRP IgG per ml, corresponding to 89, 90, and 97% of infants receiving three doses of either the full concentration or one-half or one-third of the labeled concentration, respectively. This approach offers an alternative strategy for the prevention of H. influenzae type b disease in countries with limited resources. 相似文献
16.
Differential effect of systemic acyclovir treatment of genital HSV-2 infections on antibody responses to individual HSV-2 proteins 总被引:4,自引:0,他引:4
Western blot and reflectance densitometry were used to evaluate the antibody response from patients treated with systemic acyclovir during their primary episodes of genital HSV-2 infection. Of 39 patients studied, 10 received oral acyclovir, 10 received intravenous acyclovir, and 19 received placebo. Total antibody levels as well as levels of antibodies to individual HSV-2 proteins (gB, gG, gC/gE, VP16, gD, and p45) were determined in convalescent phase sera. The median number of HSV-2 proteins recognized and the total amount of HSV-2 antibody were significantly lower in acyclovir than placebo treated patients (P less than or equal to 0.01). Levels of antibodies to individual proteins were also lower in sera from acyclovir versus placebo treated patients: gB (P = 0.013), gC/gE (P = 0.017), VP16 (P = 0.001), gD (P = 0.009), and p45 (P = 0.015). Antibody response to gG-92 and to a newly described gG species, gG-70, was not significantly different among treatment groups. A low number of proteins recognized by convalescent serum antibodies were associated with a higher number of lesions at first recurrence (P = 0.02) and with a longer duration of the first recurrent episode (P = 0.02). Low levels of total antibody were associated with shorter times to first recurrence (P = 0.05). Low levels of antibody to VP16 (P = 0.05) and gD (P = 0.01) were associated with longer duration of the first recurrence. 相似文献
17.
Regulation of Fungal Infection by a Combination of Amphotericin B and Peptide 2, a Lactoferrin Peptide That Activates Neutrophils
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Tetsuro Okamoto Toyohiro Tanida Benjuan Wei Eisaku Ueta Tetsuya Yamamoto Tokio Osaki 《Clinical and Vaccine Immunology : CVI》2004,11(6):1111-1119
To establish a novel strategy for the control of fungal infection, we examined the antifungal and neutrophil-activating activities of antimicrobial peptides. The duration of survival of 50% of mice injected with a lethal dose of Candida albicans (5 × 108 cells) or Aspergillus fumigatus (1 × 108 cells) was prolonged 3 to 5 days by the injection of 10 μg of peptide 2 (a lactoferrin peptide) and 10 μg of α-defensin 1 for five consecutive days and was prolonged 5 to 13 days by the injection of 0.1 μg of granulocyte-monocyte colony-stimulating factor (GM-CSF) and 0.5 μg of amphotericin B. When mice received a combined injection of peptide 2 (10 μg/day) with amphotericin B (0.5 μg/day) for 5 days after the lethal fungal inoculation, their survival was greatly prolonged and some mice continued to live for more than 5 weeks, although the effective doses of peptide 2 for 50 and 100% suppression of Candida or Aspergillus colony formation were about one-third and one-half those of amphotericin B, respectively. In vitro, peptide 2 as well as GM-CSF increased the Candida and Aspergillus killing activities of neutrophils, but peptides such as α-defensin 1, β-defensin 2, and histatin 5 did not upregulate the killing activity. GM-CSF together with peptide 2 but not other peptides enhanced the production of superoxide (O2−) by neutrophils. The upregulation by peptide 2 was confirmed by the activation of the O2−-generating pathway, i.e., activation of large-molecule guanine binding protein, phosphatidyl-inositol 3-kinase, protein kinase C, and p47phox as well as p67phox. In conclusion, different from natural antimicrobial peptides, peptide 2 has a potent neutrophil-activating effect which could be advantageous for its clinical use in combination with antifungal drugs. 相似文献
18.
Fredrik Oftung Gro Ellen Korsvold Audun Aase Lisbeth M. N?ss 《Clinical and Vaccine Immunology : CVI》2016,23(4):353-362
MenBvac and MeNZB are safe and efficacious outer membrane vesicle (OMV) vaccines against serogroup B meningococcal disease. Antibody responses have previously been investigated in a clinical trial with these two OMV vaccines given separately (25 μg/dose) or in combination (12.5 and 12.5 μg/dose) in three doses administered at 6-week intervals. Here, we report the results from analyzing cellular immune responses against MenBvac and MeNZB OMVs in terms of antigen-specific CD4+ T cell proliferation and secretion of cytokines. The proliferative CD4+ T cell responses to the combined vaccine were of the same magnitude as the homologous responses observed for each individual vaccine. The results also showed cross-reactivity in the sense that both vaccine groups receiving separate vaccines responded to both homologous and heterologous OMV antigen when assayed for antigen-specific cellular proliferation. In addition, a multiplex bead array assay was used to analyze the presence of Th1 and Th2 cytokines in cell culture supernatants. The results showed that gamma interferon, interleukin-4 (IL-4), and IL-10 responses could be detected as a result of vaccination with both the MenBvac and the MeNZB vaccines given separately, as well as when given in combination. With respect to cross-reactivity, the cytokine results paralleled the observations made for proliferation. In conclusion, the results demonstrate that cross-reactive cellular immune responses involving both Th1 and Th2 cytokines can be induced to the same extent by different tailor-made OMV vaccines given either separately or in combination with half the dose of each vaccine. 相似文献
19.
J I Sin V Ayyavoo J Boyer J Kim R B Ciccarelli D B Weiner 《International immunology》1999,11(11):1763-1773
A central tenet of vaccine development is to identify immune correlates of protection. Both plasmid-encoded gD as well as recombinant protein gD can protect mice from lethal herpes simplex virus (HSV) challenge. It is known that different vaccine modalities should induce different immune phenotypes. Yet, paradoxically, it is also thought that the basis for protection should rely on exploitation of vulnerabilities of the pathogen and therefore that the overlapping properties of these different vaccines would reveal insight into common immune mechanisms responsible for protection. We sought to investigate this question by comparing two different vaccine modalities in the HSV-2 mouse model. We observed that gD protein was a strong inducer of T(h)2-type immune responses, and overall antibody titers of IgG, IgE and IgA were significantly higher than those induced by plasmid gD vaccines. In contrast, the plasmid gD vaccine induced a strong T(h)1 bias. Following high-dose challenge the gD protein was most effective at providing protection. However, at lower lethal dose challenge, while both vaccines were protective with regards to survival, only the plasmid-vaccinated animals were protected from HSV-2 infection-induced morbidity. These studies suggest that these different vaccine modalities induce protection through unique non-overlapping mechanisms, supporting that vaccine correlates are associated with the types of immunogen rather than solely the pathogen. 相似文献
20.
Chiaki Miyazaki Kenji Okada Takao Ozaki Mizuo Hirose Kaneshige Iribe Hiroyuki Yokote Yuji Ishikawa Takehiro Togashi Kohji Ueda 《Clinical and Vaccine Immunology : CVI》2014,21(2):188-195
The immunogenicity and safety of an inactivated cell culture Japanese encephalitis vaccine (CC-JEV) were compared with those of an inactivated mouse brain-derived Japanese encephalitis vaccine (MB-JEV) in phase III clinical multicenter trials conducted in children. The vaccines contain the same Japanese encephalitis virus strain, the Beijing-1 strain. Two independent clinical trials (trials 1 and 2) were conducted. Trial 1 was conducted in 468 healthy children. Each subject was injected with 17 μg per dose of either CC-JEV or MB-JEV, and the immunogenicity and safety of the vaccines were investigated. Trial 1 showed that CC-JEV was more immunogenic and reactive than MB-JEV at the same dose. Therefore, to adjust the immunogenicity of CC-JEV to that of MB-JEV, a vaccine that has had a good track record regarding its efficacy for a long time, trial 2 was conducted in 484 healthy children. To improve the stability, CC-JEV was converted from a liquid type to a freeze-dried type of vaccine. Each subject was injected subcutaneously with either 4 μg per dose of CC-JEV, 8 μg per dose of CC-JEV, or 17 μg per dose of MB-JEV twice, at an interval of 2 to 4 weeks, followed by an additional booster immunization 1 to 15 months after the primary immunization. Based on the results of trial 2, 4 μg per dose of the freeze-dried CC-JEV (under the label Encevac) was selected as a substitute for the MB-JEV. Encevac was approved and launched in 2011 and has since been in use as a 2nd-generation Japanese encephalitis vaccine in Japan. (These studies have been registered at the JapicCTI under registration no. JapicCTI-132063 and JapicCTI-080586 for trials 1 and 2, respectively.) 相似文献