A DNA-prime/protein-boost vaccination regimen enhances Th2 immune responses but not protection following Schistosoma mansoni infection

DNA immunization represents a promising vaccine strategy that has been reasonably successful, and will likely play an even greater role in vaccine development as these vaccines continue to be improved. We have developed a partially protective DNA vaccine against schistosome infection based on a 23-kDa integral membrane protein, Sm23. The focus of this study was to compare immunogenicity and efficacy of vaccination regimens utilizing Sm23 DNA vaccine alone vs. regimens that utilized both Sm23 DNA and Sm23 in recombinant protein form. We found that priming and boosting with the Sm23 DNA construct (Sm23-pcDNA) resulted in a significant level of protection against challenge infection (36-44%). In contrast, altering this protocol by changing the boost from Sm23 DNA to boosting with recombinant Sm23 protein (rSm23) formulated in aluminium hydroxide (alum) failed to induce a significant reduction in worm burdens. Similarly, mice primed and boosted with the rSm23 in alum also did not develop significant levels of protection against challenge infection. We hypothesize that the differences in the ability to drive protective immunity using the DNA prime-DNA boost strategy and the inability to do so when recombinant Sm23 in alum was substituted for Sm23 DNA is due to driving of different immune responses. In support of this, we found that mice primed and boosted with Sm23-pcDNA had Th1-type immune responses characterized by low anti-Sm23 IgG1 : IgG2a antibody isotype ratios, whereas mice boosted with rSm23 had higher IgG1 : IgG2a ratios. In addition, priming and boosting with rSm23 elicited mainly IgG1 antibodies with no detectable IgG2a, indicative of a polarized Th2-type immune response. Thus, similar to our earlier work, the results of this study show that protective vaccination using Sm23 is associated with a Th1 immune response, and efficacy is diminished using protocols that diminish this Th1 bias. In our study, this was likely due to the use of the Th2-driving adjuvant alum, and future studies are planned where we will compare the protective efficacy of rSm23 administered with Th1-type adjuvants.     

以恶性疟原虫裂殖子表面蛋白1的17区片段基因为基础的复合核酸疫苗诱导小鼠体液免疫反应的研究

目的: 检测以恶性疟原虫裂殖子表面蛋白1 的17 区片段基因为基础的复合核酸疫苗VR1012/TPA/HG-MSP1-17(分泌性)和VR1012/HG-MSP1-17(非分泌性)诱导小鼠的体液免疫反应。方法: 分别用分泌性与非分泌性核酸疫苗肌注免疫小鼠。用间接ELISA法测定小鼠血清的特异性抗体。结果: 每只小鼠经3 次100 μg/100μl非分泌性核酸疫苗免疫后, BALB/c小鼠和C57BL/6 小鼠均产生明显的抗HG和抗真菌表达的MSP1 17 区蛋白(YMSP119 )抗体。但总体抗体水平不高。BALB/c小鼠经3 次200 μg/100 μl非分泌性核酸疫苗免疫后, 产生较高的抗HG抗体, 但抗MSP1-17 的抗体无明显变化。经3 次200 μg/100 μl分泌性核酸疫苗免疫后, 只产生较低的抗HG抗体。结论: 非分泌性核酸疫苗较分泌性核酸疫苗具有更强的免疫原性     

以恶性疟原虫MSP1和AMA1疫苗组合免疫小鼠诱导保护性免疫

目的以MSP1和AMA1的DNA疫苗、重组痘苗病毒疫苗和重组蛋白疫苗组合免疫小鼠,诱导针对疟疾红内期抗原MSP1和AMA1的保护性抗体。方法将编码恶性疟原虫MSP1全片段和AMA1胞外域的DNA免疫质粒(VR1020/190.3和VR1020/E)、痘苗病毒载体(rMVA/190.3和rMVA/E)及重组蛋白(d-GX190H和E)的同种类型疫苗混合,作为核酸疫苗(D)、病毒疫苗(V)及蛋白疫苗(P)按照“初始-强化”策略免疫小鼠。间接ELISA测血清中抗MSP1和AMA1抗体;用免疫血清进行体外原虫入侵红细胞抑制实验;由转基因伯氏疟原虫Pb-PfM19和P.bANKA株分别对免疫鼠进行体内攻击。结果各组免疫血清中均产生了较强的抗体应答,抗MSP1抗体与抗AMA1抗体滴度的变化趋势一致。实验组免疫小鼠血清在体外对两株原虫入侵红细胞均有较大程度的抑制。体内攻击实验中实验组小鼠平均存活时间较对照组略长。结论采用以MSP1和AMA1为基础的DNA、重组痘苗病毒和重组蛋白疫苗的组合免疫小鼠能诱导出有效的保护性抗体。以上结果为疟疾红内期疫苗合理免疫方案提供了重要的实验依据。     

DNA immunization with Onchocerca volvulus genes, Ov-tmy-1 and OvB20: serological and parasitological outcomes following intramuscular or GeneGun delivery in a mouse model of onchocerciasis

The objective of this study was to evaluate whether the distinct immune responses invoked by epidermal and intramuscular DNA immunization could be harnessed to improve upon the levels of protection to Onchocerca volvulus infective larvae achieved previously by recombinant protein immunization. Intramuscular (IM) and epidermal (GeneGun) routes of DNA immunization generally drive T helper1 and Th2 dominant responses, respectively. This dichotomy was used in an attempt to further define the nature of host-protective immunity in a mouse model of onchocerciasis. Mice were immunized with DNA plasmids expressing the O. volvulus antigens, Ov-TMY-1 (tropomyosin) and OvB20 (a nematode specific gene product). While, IM and GeneGun immunization of mice with Ov-tmy-1 induced expected Th1/Th2-associated IgG isotype profiles, mice responded to OvB20 immunization with a Th2 dominant response, irrespective of the delivery route. Despite inducing potent serological responses, neither DNA construct promoted statistically significant levels of protection to L3 challenge infection. We conclude that DNA immunization has good potential for induction of humoral responses against nematode infections and that serological responses alone do not predict vaccination efficacy under the conditions used here to measure host resistance to parasite challenge.     

恶性疟原虫Pf12基因重组质粒DNA接种诱导小鼠的免疫应答

目的　观察重组质粒VR10 12 -Pf12DNA直接免疫接种诱导BALB/c小鼠所产生的免疫应答 ,分析Pf12基因的抗原性和作为疫苗抗原候选分子的可能性。方法　构建重组质粒VR10 12 -Pf12 ,直接免疫BALB/c小鼠 ,通过NK细胞杀伤活性、脾T淋巴细胞增殖水平、ELISA、体外抑虫试验测定 ,观察其诱导的细胞和体液应答以及体外抑虫效果。结果　重组质粒VR10 12 -Pf12免疫BALB/c小鼠 ,NK细胞杀伤活性、脾T淋巴细胞增殖水平明显高于对照组 (P <0 0 1) ,诱导小鼠产生的抗体水平明显增高 (P <0 0 1) ,免疫血清在体外能抑制恶性疟原虫的生长、发育。结论　重组质粒VR10 12 -Pf12DNA直接免疫接种诱导BALB/c小鼠产生一定水平的体液和细胞免疫应答 ,其免疫血清在体外对恶性疟原虫的生长、发育有明显的抑制作用。     

DNA-based vaccination induces humoral and cellular immune responses against hepatitis B virus surface antigen in mice without activation of C-myc

AIM To develop a safe and effective DNA vaccine for inducing humoral and cellular immunological responses against hepatitis B virus surface antigen (HBsAg). METHODS BALB/c mice were inoculated with NV-HB/s, a recombinant plasmid that had been inserted S gene of hepatitis B virus genome and could express HBsAg in eukaryotes. HBsAg expression was measured by ABC immunohistochemical assay, generation of anti-HBs by ELISA and cytotoxic T lymphocyte (CTL), by MTT method, existence of vaccine DNA by Southern blot hybridization and activation of oncogene C-myc by in situ hybridization.RESULTS With NV-HB/s vaccination by intramuscular injection, anti-HBs was initially positive 2 weeks after inoculation while all mice tested were HBsAg positive in the muscles. The titers and seroconversion rate of anti-HBs were steadily increasing as time went on and were dose-dependent. All the mice inoculated with 100 μg NV-HB/ s were anti-HBs positive one month after inoculation, the titer was 1:1024 or more. The humoral immune response was similar induced by either intramuscular or intradermal injection. CTL activities were much stronger (45.26%) in NV-HB/s DNA immunized mice as compared with those (only 6%) in plasmaderived HBsAg vaccine immunized mice. Two months after inoculation, all muscle samples were positive by Southern-blot hybridization for NV-HB/s DNA detection, but decreased to 25%and all were undetectable by in situ hybridization after 6 months. No oncogene Cmyc activation was found in the muscle of inoculation site. CONCLUSION NV-HB/s could generate humoral and cellular immunological responses against HBsAg that had been safely expressed in situ by NV-HB/s vaccination.     

细胞因子表达质粒对恶性疟原虫顶端膜抗原1DNA免疫的调节作用

目的　探讨细胞因子表达质粒对小鼠DNA免疫的促进和调节作用。　方法　构建编码恶性疟原虫顶端膜抗原1(AMA1)完整胞外域的DNA免疫质粒VR1020/E,构建编码小鼠细胞因子(GMCSF)、白细胞介素(IL)如IL4和IL12的真核表达质粒pcDNA3/GMCSF、pcDNA3.1( ) /IL4和pIL12以及双顺反子质粒pGM CSF/pTPA E,分组免疫小鼠,ELISA检测血清中特异性IgG及其亚类的水平,取小鼠脾细胞进行体外增殖。　结果　 3种细胞因子质粒均有效增强了小鼠针对VR10 20/E的免疫应答,抗体水平增加7至10倍,其中pcDNA3/GMCSF质粒和pIL12质粒分别显著促进了小鼠的IgG1和IgG2a应答,小鼠脾细胞的体外增殖水平亦有明显提高。　结论　利用编码GM CSF、IL4和IL12的表达质粒作为佐剂可有效增强小鼠针对AMA1DNA的免疫应答,并对免疫应答的类型产生调节作用。     

Induction of protective immunity for Bordetella pertussis by nasal inoculation of pertussis vaccine in mice

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.     

日本血吸虫二价DNA疫苗的免疫保护效果研究

目的观察本课题组所构建日本血吸虫大陆株二价DNA疫苗VR101 2-SjGST-Sj31和VR1012-SjGST-Sj32的免疫保护效果.方法用纯化质粒免疫昆明鼠:60只小鼠分为5组,2个对照组的小鼠分别于股四头肌注射生理盐水100μl或空质粒VR1012 100μg,3个实验组的小鼠则同法分别注射VR1012-SjGST、VR1012-SjGST-Sj31和VR1012-SjGST-Sj32各100μg,每隔3周免疫1次,共免疫3次,以间接免疫荧光法观察VR1012-SjGST-Sj31、VR1012-SjGST-Sj32在肌肉组织中的表达后,每只鼠经腹部感染10条尾蚴,45 d后剖杀计数各小鼠成虫数及肝卵数,并用ELISA分析小鼠血清中的抗体.结果ELISA分析表明,第3次免疫后小鼠出现特异性IgG抗体.与生理盐水组比较,3个实验组的减虫率分别为33.90%、33.90%及27.14%(P＜0.01),减卵率分别为61.86%、74.88%及68.87%(均为P＜0.01),每雌肝减卵率分别为44.67%、59.40%、54.32%(P＜0.01).与VR1 012-SjGST组相比,VR1012-SjGST-Sj31和VR1012-SjGST-Sj32组的减卵率分别为34.19%(P＜0.01)、1 8.51%(P＜0.01),每雌肝减卵率为26.62%、17.46%(P＜0.01).结论DNA疫苗VR101 2-SjGST-Sj31和VR1012-SjGST-Sj32能在组织中正常表达,能诱导小鼠产生一定水平的抗日本血吸虫感染保护作用,二价疫苗的抗生殖免疫效果要大于单价疫苗.     

Humoral response in hamsters following vaccination with cDNA encoding acey-1 cysteine proteinase of Ancylostoma ceylanicum

The humoral response in hamsters following vaccination against Ancylostoma ceylanicum infections with DNA construct was investigated. Groups of hamsters were injected intramuscularly with plasmid pcDNA 3.1. containing cDNA of ACEY-1 cysteine proteinase. Vaccination resulted in IgG antibody response to somatic extracts of adult A. ceylanicum. The highest level of antibodies was observed seven weeks after vaccination.     

Plasmid DNA immunization against Japanese encephalitis virus: immunogenicity of membrane-anchored and secretory envelope protein.

Plasmid DNA synthesizing membrane-anchored or secretory Japanese encephalitis virus (JEV) envelope (E) protein and premembrane protein was delivered to mice by intramuscular injection or gene gun. Intramuscular plasmid immunization induced anti-E antibody responses similar to those associated with commercial JEV vaccine. The gene gun induced less antibody response. The 2 forms of the E protein induced similar antibody titers when administered by the same delivery mode. Both plasmids generated high titers of JEV-neutralizing antibodies, although the titers were lower than those induced by the vaccine. Intramuscular DNA immunization induced T helper 1 (Th1) immune responses, and the gene gun induced Th2 responses. Compared with secretory E protein, the membrane-anchored protein heavily skewed the immune response toward either Th1 or Th2, depending on the route of immunization. In an intracerebral JEV challenge model, plasmid-immunized mice had approximately 60% protection; this was not affected by the form of the E protein or by immunization route.     

信号肽和辅助性T细胞表位以及GST表位增强猪带绦虫保护性抗原诱导免疫应答的初步研究

目的：研究信号肽和辅助性T细胞表位以及GST表位增强猪带绦虫保护性抗原诱导的免疫应答。方法：在猪绦虫融合抗原pCC27(本室从六钩蚴cDNA表达文库筛选的三个保护性抗原经拼接所得)基因片段5′末端引入人IL-2信号肽、一个通用型辅助性T淋巴细胞表位，谷胱甘肽还原酶的T和B淋巴细胞表位(TGG)，经pGEX4T-2表达鉴定，序列分析后构建成DNA疫苗，通过肌肉注射途径将这种DNA疫苗免疫小鼠。结果：这种含辅助表位的DNA疫苗诱导的免疫应答效果明显超过对照组，对绦虫卵攻击的保护率为90％。结论：构建了含绦虫融合抗原pCC27及TGG的核酸疫苗，动物试验结果表明．TGG表位既可提高IgG、IgG1、IgG2a的水平，又进一步增强Th1和Th2细胞间的平衡关系。免疫小鼠对绦虫卵的攻击具有很好的保护作用。     

Sm‐p80‐based DNA vaccine made in a human use approved vector VR1020 protects against challenge infection with Schistosoma mansoni in mouse

Although there is an effective drug (praziquantel) available for the treatment of schistosomiasis, yet the disease is still spreading unabated and is rampant in 76 countries. Control via praziquantel treatment has so far been insufficient in reducing the disease transmission. Therefore, a vaccine in addition to other strategies, for example, improving sanitation and introduction of new drugs are essential to successfully control and eventually eradicate schistosomiasis. To this effect, we have targeted a functionally important antigen, Sm‐p80 as a vaccine candidate. In this study, full length cDNA of Sm‐p80 was cloned in VR1020, a FDA approved vector for human use. The protective efficacy of this vaccine formulation was tested in a murine model. Sm‐p80‐VR1020 vaccine formulation was able to induce 47% reduction in worm burden. Serology on samples obtained from vaccinated animals revealed a strong antibody response which included IgG and all of its subtypes, IgM and IgA. Proliferating splenocytes in response to recombinant Sm‐p80 produced a wide spectrum of cytokines representing Th1, Th2 and Th17 types, as ascertained via RT‐PCR analysis. These findings further strengthen the importance of Sm‐p80 molecule as a vaccine candidate for intestinal schistosomiasis.     

乙型肝炎病毒复制调控元件对HBV DNA疫苗诱导的免疫应答

目的研究乙型肝炎病毒（HBV）复制调控元件增强子Ⅰ（ENHⅠ）及前S2（Pre-S2）抗原基因对HBV DNA疫苗诱导的免疫应答的影响。方法采用常规聚合酶链反应（PCR）从HBV adr亚型全基因DNA序列中分别扩增HBsAg、PreS2-HBsAg、HBsAg-ENHI和PreS2-HBsAg-ENHⅠ基因片段，重组到VR1012载体中，构建4种HBV DNA疫苗，转染HepG2细胞并免疫Balb／C小鼠。通过细胞免疫化学、酶联免疫分析（ELISA）、酶联免疫斑点试验（ELISPOT）等方法检测其在HepG2细胞内的表达及小鼠的体液及细胞免疫应答。结果转染的HepG2细胞表达相应的目的蛋白．ENHⅠ及Pre-S2抗原基因均可增强HBV DNA疫苗转染HepG2细胞表达HBsAg；免疫接种小鼠后第2周产生抗-HBs及HBsAg特异性细胞毒T淋巴细胞（CTL），Pre—S2抗原基因可增强HBV DNA疫苗免疫Balb／C小鼠诱导的抗-HBs及HBsAg特异性CTL的产生，ENHⅠ基因对免疫应答无影响。结论ENHI及Pre—s2抗原基因均可增强HBVDNA疫苗转染HepG2细胞表达HBsAg．Pre-S2抗原基因可增强HBVDNA疫苗免疫Balb／C小鼠引起的免疫应答。     

An SHIV DNA/MVA rectal vaccination in macaques provides systemic and mucosal virus-specific responses and protection against AIDS

We explored the use of a simian-human immunodeficiency virus (SHIV) DNA vaccine as an effective mucosal priming agent to stimulate a protective immune response for AIDS prevention. Rhesus macaques were vaccinated rectally with a DNA construct producing replication-defective SHIV particles, and boosted with either the same DNA construct or recombinant modified vaccinia virus Ankara (MVA) expressing SIV Gag, SIV Pol, and HIV Env (MVA-SHIV). Virus-specific mucosal and systemic humoral and cell-mediated immune responses could be stimulated by this approach but were present inconsistently among the vaccinated animals. Rectal vaccination with either SHIV DNA alone or SHIV DNA followed by MVA-SHIV induced SIV Gag/Pol- or HIV gp120-specific IgA in rectal secretions of four of seven animals. However, the gp120-specific rectal IgA antibody responses were not durable and had become undetectable in all but one animal shortly before rectal challenge with pathogenic SHIV 89.6P. Only the macaques primed with SHIV DNA and boosted with MVA-SHIV demonstrated SHIV-specific IgG in plasma. In addition, these animals developed more consistent antiviral cell-mediated responses and had better preservation of CD4 T cells following challenge with SHIV 89.6P. Our study demonstrates the utility of a rectal DNA/MVA vaccination protocol for the induction of diverse responses in different immunological compartments. In addition, the immunity achieved with this mucosal vaccination regimen is sufficient to delay progression to AIDS.     

Priming with plasmid DNAs expressing interleukin-12 and simian immunodeficiency virus gag enhances the immunogenicity and efficacy of an experimental AIDS vaccine based on recombinant vesicular stomatitis virus

Of the various approaches being developed as prophylactic HIV vaccines, those based on a heterologous plasmid DNA prime, live vector boost vaccination regimen appear especially promising in the nonhuman primate/simian-human immunodeficiency virus (SHIV) challenge model. In this study, we sought to determine whether a series of intramuscular priming immunizations with a plasmid DNA vaccine expressing SIVgag p39, in combination with plasmid expressed rhesus IL-12, could effectively enhance the immunogenicity and postchallenge efficacy of two intranasal doses of recombinant vesicular stomatitis virus (rVSV)-based vectors expressing HIV-1 env 89.6P gp160 and SIVmac239 gag p55 in rhesus macaques. In macaques receiving the combination plasmid DNA prime, rVSV boost vaccination regimen we observed significantly increased SIVgag- specific cell-mediated and humoral immune responses and significantly lower viral loads postintravenous SHIV89.6P challenge relative to macaques receiving only the rVSV vectored immunizations. In addition, the plasmid DNA prime, rVSV boost vaccination regimen also tended to increase the preservation of peripheral blood CD4+ cells and reduce the morbidity and mortality associated with SHIV89.6P infection. An analysis of immune correlates of protection after SHIV89.6P challenge revealed that the prechallenge SHIV-specific IFN-gamma ELISpot response elicited by vaccination and the ability of the host to mount a virus-specific neutralizing antibody response postchallenge correlated with postchallenge clinical outcome. The correlation between vaccine-elicited cell-mediated immune responses and an improved clinical outcome after SHIV challenge provides strong justification for the continued development of a cytokine-enhanced plasmid DNA prime, rVSV vector boost immunization regimen for the prevention of HIV infection.     

Application of SCR priming VLP boosting as a novel vaccination strategy against HIV-1

Human immunodeficiency virus infection is a worldwide health problem and a protective vaccine is desperately needed to control the AIDS pandemics. To address this concern, we previously constructed single-cycle replicable (SCR) HIV-1 virions, which completely maintained the antigenic structures of HIV-1. Herein, to optimize a vaccination strategy, we studied the immunogenicity of produced SCR virions and adjuvant-formulated HIV-1 virus-like particles (VLPs) in homologous and heterologous prime-boosting regimens. Accordingly, BALB/c mice received three doses of immunogens in 3-week intervals and their immune responses were evaluated using ELISA, cytokine and IFN-γ ELISpot assays. These analyses not only indicated the superiority of SCR prime-VLP boosting for strong induction of specific IFN-γ producing cells, but also showed the capability of this strategy over the others for better stimulation of humoral response, which was evidenced with the detection of highest titer of total IgG against HIV ENV glycoprotein. Furthermore, determination of IgG subclasses and IFN-γ/IL4 secretion ratio in cultured splenocytes demonstrated the efficient augmentation of mixed responses with the dominancy of Th1 immunity following SCR/VLP immunization strategy. Our results additionally pointed towards the applicability of Montanide ISA 720 + CpG as a potent Th1-directing adjuvant mixture. Overall, this study suggests SCR prime-VLP boosting as a promising approach in HIV vaccine development.     

以恶性疟原虫裂殖子表面蛋白1的17区片段基因为基础构建的复合核酸疫苗候选质粒

目的 :构建以恶性疟原虫裂殖子表面蛋白 1的 17区基因为基础的复合核酸疫苗。方法 :将恶性疟原虫 FUP株 MSP1的 17区基因片段与包含若干个内源性和外源性 T细胞位点相应的基因片段相连 ,构成复合基因 ( hybrid gene,HG) ,将其分别克隆入非分泌性真核表达载体 [VR10 12和 p CDNA3.1( - ) ]和经改建后的分泌型载体 VR10 12 /TPA中 ,通过 PCR和酶切鉴定重组克隆。结果和结论 :经鉴定复合基因正确地克隆入真核表达载体 ,成功地构建了 VR10 12 /HG,p CD-NA3.1/HG和 VR10 12 /TPA/HG。结论 :为探讨疟疾核酸疫苗的效果及 T细胞位点的作用打下了基础。     

The immune response to influenza vaccination in diabetic patients

Summary The immune response of diabetic patients to influenza vaccination was examined in 31 patients, 10 with Type 1 (insulin-dependent) diabetes and 21 with Type 2 (non-insulin-dependent diabetes), and in 19 normal subjects. Each received a single intramuscular injection of the 3 virus strains (A/Chile,A/Philippines,B/USSR) anti-influenza vaccine recommended by WHO. The antibody titre and the cell-mediated immune response to the 3 virus strains, as evaluated by the generation of activated lymphocytes and enumeration of B lymphocytes, were studied before and 18 h, 72 h and 1, 2, 3 and 6 weeks after vaccination. Overall, the humoral and cell-mediated immune responses were normal in both groups of patients. However, patients with Type 1 diabetes showed a statistically significant increase (p< 0.01) of antibody titre of the A/Chile and an increased percentage of B lymphocytes one week after vaccination compared to age-matched control subjects. Four out of 21 patients with Type 2 diabetes had no antibody response to all 3 virus strains. A significant reduction (p< 0.01) of the percentage of activated cells possessing receptors for interleukin-2 was observed 72 h after vaccination in patients with Type 2 diabetes compared to age-matched control subjects. None of the patients who received the vaccine developed influenza in the course of the following year. These results suggest that valid protection against the influenza virus can be obtained in patients with Type 1 and Type 2 diabetes.     

Duration of immunity after hepatitis B vaccination: efficacy of low-dose booster vaccine

Although the efficacy of hepatitis vaccine is well documented, the duration of immunity of healthy adults after vaccination is unknown. We studied 245 hospital employees 3 years after primary vaccination with hepatitis B vaccine to determine the prevalence of immunity indicated by levels of antibody to hepatitis B surface antigen of 10 mIU/mL or greater; and to compare the immunogenicity of low-dose intradermal vaccine with standard-dose intramuscular vaccine in persons found to be seronegative. Thirty-eight percent of employees studied had antibody levels less than 10 mIU/mL. Low levels were associated with smoking, older age, and higher body-mass index. Seventy-eight percent of persons with low antibody levels responded to a single booster vaccine. Two micrograms of intradermal vaccine was as effective as 20 micrograms of intramuscular vaccine in inducing an antibody response; however, intradermal vaccine was associated with more local reactions (42% compared with 17%). Many healthy adults will need periodic boosters of hepatitis B vaccine to maintain production of antibody to hepatitis B surface antigen; low-dose intradermal booster schedules may be feasible.