接种Aβ42全肽疫苗恒河猴的特异性体液免疫应答

目的 观察恒河猴接种Aβ42肽疫苗后的特异性抗体的产生. 方法 将5只雄性恒河猴分别在0、 2、 6、 10、 14、 18、 22 wk肌内注射Aβ42肽疫苗; 用ELISA法检测恒河猴血清抗Aβ42抗体水平及IgG亚类; 用Western blot检测血清抗Aβ42抗体的特异性; 免疫组化染色法观察抗血清对Tg2576转基因小鼠脑组织中Aβ斑的识别. 结果 疫苗接种后第8周, 恒河猴血清中出现明显的抗Aβ42抗体, 抗体水平随着接种次数的增加而升高, 第24周达1∶ 4 320, 以后抗体水平开始下降.产生的抗Aβ42抗体以IgG1和IgG2为主(IgG2/IgG1>1).血清抗Aβ42抗体具有高度特异性, 可识别Tg2576转基因小鼠脑组织中的Aβ斑. 结论 Aβ42肽疫苗可有效地诱导恒河猴产生特异性体液免疫应答.     

Characteristics of the immune response in children multiply inoculated with an inactivated influenza vaccine

The observations involved 1082 children ranging in ages from 11 to 14 years who had been annually given from one to four injections of inactivated chromatographic influenza vaccine. An additional group consisted of 242 children who after three years of vaccination with the inactivated vaccine were given a live influenza vaccine type A (H1N1) and A (H3N2) for children. The studies showed that the highest immunological effect in children was achieved after two years of vaccination with the inactivated influenza vaccine. No positive effect on the immune response in children was demonstrated by the addition of a live vaccine into the immunization schedule against the background of multiple immunizations with the inactivated one. Different types of responses in children to immunization against influenza were observed.     

Characterization of neutralizing antibodies in adults after intranasal vaccination with an inactivated influenza vaccine

The levels and properties of neutralizing antibodies in nasal wash and serum collected from five healthy adults were examined after intranasal administration of an A/Uruguay/716/2007 (H3N2) split vaccine (45 μg hemagglutinin (HA) per dose; five doses, with an interval of 3 weeks between each dose). Prior to the assays, nasal wash samples were concentrated so that the total amount of antibodies was equivalent to about 1/10 of that found in the natural nasal mucus. Vaccination induced virus-specific neutralizing antibody responses, which increased with the number of vaccine doses given. Neutralizing antibodies were produced more efficiently in the nasal passages than in the serum: A ≥4-fold increase in nasal neutralization titres was observed after the second vaccination in four out of five subjects, whereas a rise in serum neutralization titres was observed only after the fifth vaccination. Nasal and serum neutralizing antibodies were mainly found in the polymeric IgA and monomeric IgG fractions, respectively, after gel filtration. Taken together, these results suggest that intranasal administration of an inactivated split vaccine induces high levels of nasal neutralizing antibodies (primarily polymeric IgA) and low levels of serum neutralizing antibodies (primarily monomeric IgG).     

Lack of effect of vaccination with an attenuated infectious bursal disease virus on the immune response to Newcastle disease vaccination

Vaccination at either 1, 7 or 15 days of age with an attenuated strain (vaccinal strain 1-65 PV) of infectious bursal disease (IBD) virus did not suppress the immune response to Newcastle disease vaccination. These results suggest that vaccination of chickens against IBD with vaccinal strain 1-65 PV does not damage the bird's lymphoid tissues and consequently its immunological capabilities against other infectious diseases.     

Specific immune response in the respiratory tract after administration of an oral polyvalent bacterial vaccine.

An oral killed polyvalent bacterial vaccine was assessed in a double-blind trial involving healthy volunteers. Three courses of oral vaccine were given over a 2-month period; each course contained 10(10) Haemophilus influenzae and 7 X 10(9) Staphylococcus aureus organisms. Immunity was assessed by monitoring antibody in saliva and serum over a 3-month period. No evidence of a nonspecific effect on immune parameters (immunoglobulin levels and Escherichia coli antibody) was detected in saliva or serum. An increase in H. influenzae antibody in saliva was detected in 55% of subjects receiving the vaccine compared with 6.7% of the placebo group. Antibody was associated with immunoglobulin A (IgA), IgG, and IgM, but the greatest increases over preimmunization levels were detected in the IgA class. No increase in serum antibody levels was detected. Subjects with higher preimmunization levels of salivary antibody to H. influenzae were less likely to respond to the oral bacterial vaccine. No increase in S. aureus antibody was detected in saliva or serum.     

Cell-mediated immune responses of guinea pigs to an inactivated phase I Coxiella burnetii vaccine.

The ability of a killed phase I Coxiella burnetii vaccine to induce cell-mediated immune responses in guinea pigs was studied. Cell-mediated immune responses were assessed by the inhibition of macrophage migration and lymphocyte transformation assays. The macrophage migration response occurred rapidly and was detected at high levels, but was relatively short-lived. In contrast, the lymphocyte transformation response developed more slowly, and persisted for a longer period. The vaccine, given in a single dose or in two doses 1 week apart, protected guinea pigs from a subsequent virulent challenge.     

Specific immune response in the human respiratory tract following oral immunization with live typhoid vaccine

Specific antibody responses in the lower respiratory tract of human subjects to orally administered Salmonella typhi Ty21a are reported. These responses, predominantly of the immunoglobulin G class, were determined to be a transudate from serum. These results were supported by the similarity in responses to parenteral administration of heat-killed typhoid vaccine. Specific immunoglobulin A antibody was a poor contributor to the respiratory antibody response to either vaccine.     

Local and systemic immune response in community-dwelling elderly after intranasal or intramuscular immunization with inactivated influenza vaccine

Intramuscular (IM) influenza vaccines are about 50% effective in preventing clinical illness among the elderly and their effectiveness in eliciting mucosal response may be even lower. The aim of the present study was to evaluate the immunological effect of a novel inactivated intranasal (IN) trivalent whole influenza virus vaccine among community-dwelling elderly. Sixty-one subjects were vaccinated with two doses of an IN vaccine and a control group of 31 subjects was vaccinated with a commercial IM vaccine. Viral strains in the 1997/8 vaccine used were A/Nanchang/933/95(H3N2), A/Johannesburg/82/96(H1N1) and B/Harbin/7/94. Serum IgG and nasal IgA were determined by HI and ELISA, respectively. Only a few minor local adverse events were reported after vaccination. Seroconversion for the three antigens tested was higher after IM vaccination, although not statistically significant. Local antibody response to the three antigens tested was detected in 50-53% and 19-26% of IN and IM immunized subjects, respectively. The IN vaccine tested was significantly more effective than the IM vaccine in inducing mucosal IgA response. This may prevent influenza at its early stages and thus contribute to the reduction of complications in the elderly.     

Influenza virus: immunity and vaccination strategies. Comparison of the immune response to inactivated and live, attenuated influenza vaccines

Influenza virus is a globally important respiratory pathogen which causes a high degree of morbidity and mortality annually. The virus is continuously undergoing antigenic change and thus bypasses the host's acquired immunity to influenza. Despite the improvement in antiviral therapy during the last decade, vaccination is still the most effective method of prophylaxis. Vaccination induces a good degree of protection (60-90% efficacy) and is well tolerated by the recipient. For those at risk of complications from influenza, annual vaccination is recommended due to the antigenic changes in circulating strains. However, there is still room for improvement in vaccine efficacy, long-lasting effect, ease of administration and compliance rates. The mucosal tissues of the respiratory tract are the main portal entry of influenza, and the mucosal immune system provides the first line of defence against infection. Secretory immunoglobulin A (SIgA) and IgM are the major neutralizing antibodies directed against mucosal pathogens. These antibodies work to prevent pathogen entry and can function intracellularly to inhibit replication of virus. This review describes influenza virus infection, epidemiology, clinical presentation and immune system response, particularly as it pertains to mucosal immunity and vaccine use. Specifically, this review provides an update of the current status on influenza vaccination and concentrates on the two main types of influenza vaccines currently in use, namely the cold-adapted vaccine (CAV) given intranasally/orally, and the inactivated vaccine (IV) delivered subcutanously or intramuscularly. The commercially available trivalent IV (TIV) elicits good serum antibody responses but induces poorly mucosal IgA antibody and cell-mediated immunity. In contrast, the CAV may elicit a long-lasting, broader immune (humoral and cellular) response, which more closely resembles natural immunity. The immune response induced by these two vaccines will be compared in this review.     

Humoral immune response and protection from viral infection in mice vaccinated with inactivated MHV-68: effects of type I interferon.

Infection of mice by murine gammaherpesvirus 68 (MHV-68) represents a suitable animal model in which to investigate the immune response against gammaherpesviruses and to test the efficacy of vaccination strategies. In this study, we evaluated the efficacy of heat-inactivated MHV-68 as a vaccine as well as the adjuvant activity of type I interferon (IFN-I) administered together with the vaccine. Mice vaccinated with inactivated MHV-68 and subsequently infected with the virus exhibited a significant augmentation of the virus-specific humoral immune response and a considerable inhibition of MHV-68 acute replication in the lungs compared with unvaccinated control mice. The coadministration of IFN-I with inactivated MHV-68 significantly enhanced the humoral immune response elicited by the vaccine by stimulating the production of virus-specific IgG2 antibodies but did not significantly enhance protection from viral challenge. We conclude that IFN-I, recently shown to exhibit a powerful adjuvant activity to a poorly immunogenic subunit vaccine in mice, can also enhance the humoral immune response when used as adjuvant of an inactivated viral vaccine, even though this effect is less marked as a result of the strong immune response elicited by the inactivated virus alone, which may also involve the contribution of endogenous IFN.     

Human antibody response to immunization with 17D yellow fever and inactivated TBE vaccine

The antibody response against flaviviruses tick-borne encephalitis (TBE), Kyasanur Forest disease (KFD), Murray Valley encephalitis (MVE), West Nile fever (WNF), Japanese B encephalitis (JE), dengue 2 (DEN-2), and yellow fever (YF) was studied in humans after administration of an inactivated TBE virus vaccine. Individuals were either prevaccinated with 17D yellow fever (experimental group) or without any previous exposure to flaviviruses (control group). The appearance of serum titres of homologous and heterologous haemagglutination inhibition (HI) antibodies, heterotypic DEN-2 neutralizing antibodies, and TBE enzyme-linked immunosorbent assay (ELISA) antibodies were examined. Individuals prevaccinated with the 17D yellow fever developed an antibody pattern that contrasted with that of the control group. This pattern was characterized as follows: (1) Predominantly anti-TBE IgG antibodies appeared earlier and in higher titres than in the control group, (2) heterologous HI antibodies cross-reacting with the WN flavivirus subgroup preceded the appearance of homologous HI antibodies, (3) a broad spectrum HI response was observed against all flaviviruses tested, and (4) low titre heterotypic DEN-2 neutralizing antibodies were formed in about half of the cases. These observations are discussed in the context of cross-reactivity, cross-protection and virus infection enhancement.     

Genomic correlates of variability in immune response to an oral cholera vaccine

Cholera is endemic to many countries. Recent major outbreaks of cholera have prompted World Health Organization to recommend oral cholera vaccination as a public-health strategy. Variation in percentage of seroconversion upon cholera vaccination has been recorded across populations. Vaccine-induced responses are influenced by host genetic differences. We have investigated association between single-nucleotide polymorphic (SNP) loci in and around 296 immunologically relevant genes and total anti-lipopolysaccharide (LPS) antibody response to a killed whole-cell vaccine, comprising LPS from multiple strains of Vibrio cholerae. Titers derived from standard vibriocidal assays were also analyzed to gain further insights on validated SNP associations. Vaccination was administered to 1000 individuals drawn from India. Data on two independent random subsets, each comprising ∼500 vaccinees, were used for discovery of genomic associations and validation, respectively. Significant associations of four SNPs and haplotypes in three genes (MARCO, TNFAIP3 and CXCL12) with AR were discovered and validated, of which two in TNFAIP3 and CXCL12 were also significantly associated with immunity (fourfold increase in vibriocidal titers). CXCL12 is a neutrophil and lymphocyte chemoattractant that is upregulated in response to V. cholerae infection. LPS in the vaccine possibly provides signals that mimic those of the live bacterium. TNFAIP3 promotes intestinal epithelial barrier integrity and provides tight junction protein regulation; possible requirements for adequate response to the vaccine. LPS is a potent activator of innate immune responses and a ligand of MARCO. Variants in this gene have been found to be associated with LPS response, but not with high vibriocidal titer level.     

Effect of vaccination schedule on immune response of Macaca mulatta to cell culture-grown Rocky Mountain spotted fever vaccine.

The effect of vaccination schedule on the immune response of Macaca mulatta to formalin-inactivated chicken embryo cell culture (CEC)-grown Rickettsia rickettsii vaccine was studied. Schedules consisted of inoculation on day 1 only, on days 1 and 15, on days 1 and 30, on days 1, 8, and 15, or on days 1, 15, and 45. Humoral antibody measured by microagglutination and indirect immunofluorescence and resistance to challenge with 10(4) plaque-forming units of yolk sac-grown R. rickettsii were assessed. Seroconversion was noted in all monkeys after the first dose of vaccine. A second dose administered 8 or 15 days after the primary infection, or a third given 7 or 30 days after the second, produced no long-term effect on antibody titer. Only monkeys given two doses of vaccine at a 30-day interval showed an increase in antibody titer during the period before challenge. Vaccination with one, two, or three doses of CEC vaccine prevented development of rash and rickettsemia after challenge. The two-dose schedules appeared to induce the highest degree of resistance to challenge, as indicated by unaltered hematological parameters and body temperature in monkeys. The one- and three-dose schedules were somewhat less effective, in that some challenged monkeys within each group displayed febrile and leukocyte responses associated with Rocky Mountain spotted fever infection. Our data suggest that administration of two doses of CEC vaccine at 15- or 30-day intervals is the immunization schedule of choice.     

Effect of age on serum immunoglobulin G subclass antibody responses to inactivated influenza virus vaccine

We previously reported an age-associated impairment of serum immunoglobulin G (IgG) antibody responses to inactivated influenza virus vaccine. The present study extends these observations by examining the IgG subclass distribution of vaccine responses measured by enzyme linked immunosorbent assay in healthy adults aged <40 (young), 40–64 (middle-aged), and ?65 (elderly) years. Serological responses in all age groups showed antibodies that were predominantly IgG1 and secondarily IgGS. Influenza antigen-specific IgG4 titers did not change following vaccination, and antibodies of the IgG2 subclass were not detected in any serum specimens. Aging was associated with a significant impairment of IgG1, but not of IgGS, antibody production. Relative differences in the magnitude and frequency of response between IgG1 and IgGS subclasses, which were present in young and middle-aged adults (viz., IgG1 > IgGS), were less apparent in the elderly. This observation was confirmed in a second analysis of IgG subclass-specific responses in a separate cohort of elderly vaccinees. These results suggest that the age-related impairment of humoral responses to inactivated influenza virus vaccine is primarily accounted for by differences in IgG1 antibody production, and that IgGS antibodies make up a larger proportion of the overall serologic response in the elderly than they do in younger persons. © 1994 Wiley-Liss, Inc.     

鼠疫菌重组质粒pcDNATE/F1-V的构建及其免疫效果的研究

目的 获得含有鼠疫F1和V抗原编码基因的重组质粒pcDNATE／E1-V,并测定其诱导特异性免疫应答的能力。方法PCR扩增鼠疫菌F1和V编码基因,分别与pGEM-T连接测序,构建pcDNATE／F1-V融合重组质粒,转染COS-7细胞,用Western blot方法鉴定目的蛋白的表达,重组质粒pcDNATE／E1-V加集落刺激因子(GM-CSF)免疫Balb／c小鼠,观察免疫效果。结果pcDNATE／F11-V在COS-7细胞中表达,免疫鼠体内产生特异性抗体,抗体亚型分析、细胞因子等指标的测定结果表明所构建DNA疫苗以诱发Th1型免疫为主。结论成功构建重组真核表达质粒pcDNATE／F1-V,其具有诱导特异性细胞免疫和体液免疫应答的能力,为鼠疫菌新型疫苗研制奠定了基础。     

Antibody persistence and immune memory in healthy adults following vaccination with a two-dose inactivated hepatitis A vaccine: long-term follow-up at 15 years

Long‐term persistence of vaccine‐induced immune response in adults was assessed annually for 15 years following primary immunization with a two‐dose inactivated hepatitis A vaccine. In 1992, 119 and 194 subjects aged 17–40 years and naïve for hepatitis A virus (HAV) were enrolled in two studies to receive 1,440 ELISA units (El.U) of inactivated hepatitis A vaccine (Havrix?, GlaxoSmithKline Biologicals, Belgium) according to a standard 0, 6 or an extended 0, 12 months schedule, respectively. Serum samples were taken 1 month after the second vaccine dose and every consecutive year up to 15 years after primary vaccination for measurement of anti‐HAV antibody concentrations (NCT00291876 and NCT00289757). At year 15, 100% (48/48) and 97.3% (108/111) of subjects vaccinated at 0, 6 or 0, 12 months remained seropositive for anti‐HAV antibodies, with geometric mean concentrations (GMCs) of 289.2 and 367.4 mIU/ml, respectively. An additional dose of HAV vaccine (1,440 El.U) was administered to the six subjects who had become seronegative for anti‐HAV antibodies since year 11. All subjects mounted a humoral immune response to the additional HAV challenge dose, although post‐challenge anti‐HAV antibody levels remained low in one subject. These studies represent the longest annual follow‐up of hepatitis A vaccine in healthy adults. The immune response induced by two doses of this inactivated HAV vaccine was shown to persist for at least 15 years. No difference in long‐term antibody persistence was observed between the two primary vaccination schedules, reinforcing the potential for flexibility in the timing of the second primary vaccine dose. J. Med. Virol. 83:1885–1891, 2011. © 2011 Wiley‐Liss, Inc.     

The effect of endoparasitism on the immune response to antirabies vaccination in puppies

The specific and non-specific immune response after antirabies vaccination was studied in young dogs with altered immune functions suffering from endoparasitoses and compared with those in healthy dogs. The degree of the immunosuppression was confirmed by functional test of phagocytes and proliferation activity test of lymphocytes. The study indicates an association between parasitized animals, and a depression in the immune responses. Toxocara canis, Toxascaris leonina and Trichuris vulpis were the most prevalent parasite species. During the experiment no anthelmintic treatment was applied. In puppies suffering from immunosuppression significantly lower specific antibody level after antirabies vaccination was demonstrated on day 28. In such case of known immunosuppression it is recommended to repeat antirabies vaccination; primovaccination does not provide satisfactory protection. Anthelmintic preventive treatment may be necessary to improve the immune responses to antirabies vaccination and provide effective protection.     

Blastogenic lymphocyte response as indicator of cell-mediated immunity in humans vaccinated with live and inactivated influenza vaccines

The level and dynamics of lymphocyte blastogenesis in response to phytohaemagglutinin (PHA) and to specific influenza virus antigen were studied in 3 groups of humans, vaccinated with live or inactivated whole virion influenza vaccines (H3N2 type) and placebo (control group). Both live and inactivated influenza vaccines did not change significantly the functional activity of T lymphocytes as determined by the mean values of stimulation index (SI). The analysis of individual values of PHA-dependent blastogenic response, however, revealed a decrease in SI as compared with its prevaccination level in 33.3 +/- 11.4% of the vaccinees given the live influenza vaccine.     

Influence of strain of chickens on the immune response to vaccination against Marek's disease

Field trials were conducted to determine the response of different genetic strains of commercial chickens to vaccination against Marek's disease (MD). Cell-associated and cell-free HVT vaccines conferred the same degree of protection within the same strain of chickens. The incidence of MD in vaccinated birds seemed to be correlated with the natural susceptibility of the chicken strains to the disease. Revaccination did not induce better protection in the most susceptible strain.