乙型脑炎重组痘苗病毒候选疫苗小鼠安全性评价

目的对重组痘苗病毒候选疫苗rVTT-JEVE进行动物安全性评价。方法用重组痘苗病毒rVTT-JEVE对BALB/c小鼠进行免疫接种,分别在体液免疫及细胞免疫水平上评价其免疫效果;并通过检测小鼠体内rVTT-JEVE病毒残留,分析乙型脑炎重组痘苗病毒候选疫苗rVTT-JEVE的安全性。结果 BALB/c小鼠经两次免疫接种后,重组痘苗病毒rVTT-JEVE组IgG抗体水平是商品疫苗SA-14-14-2组的1.4倍(t=3.704,P0.05),中和抗体效价是SA-14-14-2组的1.6倍(t=4.418,P0.05),T淋巴细胞增殖水平为SA-14-14-2组的1.7倍(t=3.092,P0.05)。rVTT-JEVE接种小鼠后第1d各脏器均有rVTT-JEVE病毒残留,第3d颌下淋巴结已无病毒残留,第7d仅脾脏和雄性小鼠心脏有少量病毒残留,之后均无病毒残留。结论重组痘苗病毒候选疫苗rVTT-JEVE免疫小鼠可产生较好的免疫效果及免疫安全性。     

共表达PRRSV ORF5和ORF6基因重组核酸疫苗对断奶仔猪的免疫效果研究

目的评价猪繁殖与呼吸综合征病毒(PRRSV)重组核酸疫苗pVAX-ORF5-2A-ORF6对断奶仔猪的免疫效果。方法分别以pVAX-ORF5-2A-ORF6+Quil A、pVAX-ORF5-2A-ORF6、pVAX空质粒和PRRSV弱毒疫苗对断奶仔猪进行免疫接种,检测各免疫组血清中特异性抗体效价、细胞因子IL-2、IL-4、IL-6、IFN-γ的水平、T淋巴细胞增殖程度和CTL杀伤活性,评价其免疫效果。结果重组核酸疫苗pVAX-ORF5-2A-ORF6能够刺激猪体产生PRRSV特异性抗体,促进致敏T淋巴细胞增殖,诱导产生特异性细胞毒性T淋巴细胞(CTL)杀伤活性;免疫仔猪血清IL-2和IFN-γ水平与对照组比较差异有统计学意义(P<0.05),加入免疫佐剂Quil A的实验组IFN-γ水平显著高于未加佐剂的实验组(P<0.05)。结论重组核酸疫苗pVAX-ORF5-2A-ORF6可诱导免疫仔猪产生特异性的体液免疫和细胞免疫应答,有望成为抗PRRSV感染的新型候选疫苗。     

日本血吸虫Rho GTPase DNA疫苗及重组蛋白疫苗免疫保护机制初探

目的　初步探讨日本血吸虫中国大陆株pcDNA3 .1 SjRhoGTPaseDNA疫苗、重组蛋白疫苗以及联合疫苗免疫的保护机制。　方法　将 pcDNA3 .1 SjRhoGTPaseDNA疫苗、重组蛋白疫苗分别及联合疫苗免疫昆明鼠后 ,分不同时间采集血清 ,以ELISA法测定总抗体及IgG亚类。　 结果　重组蛋白疫苗及联合疫苗诱导产生的抗体效价较高 ,DNA疫苗及联合疫苗诱导产生的抗体以IgG2a为主 ,重组蛋白疫苗诱导产生的抗体以IgG1为主。　 结论　Sj RhoGTPase基因DNA疫苗及联合疫苗主要诱生Th1型细胞免疫应答 ,重组蛋白疫苗主要诱生Th2型体液免疫应答     

日本血吸虫Rho GTPase DNA疫苗及重组蛋白疫苗免疫保护机制初探

目的 初步探讨日本血吸虫中国大陆株pcDNA3．1-SjRho GTPase DNA疫苗、重组蛋白疫苗以及联合疫苗免疫的保护机制。方法 将pcDNA3．1-SjRho GTPase DNA疫苗、重组蛋白疫苗分别及联合疫苗免疫昆明鼠后，分不同时间采集血清，以ELISA法测定总抗体及IgG亚类。结果 重组蛋白疫苗及联合疫苗诱导产生的抗体效价较高，DNA疫苗及联合疫苗诱导产生的抗体以IgG2a为主，重组蛋白疫苗诱导产生的抗体以IgG1为主。结论 Sj-Rho GTPase基因DNA疫苗及联合疫苗主要诱生Th1型细胞免疫应答，重组蛋白疫苗主要诱生Th2型体液免疫应答。     

表达口蹄疫病毒复合多表位基因的重组鸡痘病毒以及DNA疫苗在豚鼠中的免疫原性研究

目的评价本课题组构建的共表达FMDV复合多表位基因以及猪白细胞介素18基因的非复制型重组鸡痘病毒活载体疫苗vUTA2-OAT以及DNA疫苗pVRI-OAT诱导FMDV模型动物豚鼠产生特异性体液免疫和细胞免疫的能力。方法将上述2种重组疫苗分别单独或联合接种豚鼠,然后测定FMDV特异性结合抗体、中和抗体和T淋巴细胞增殖反应,并用250ID50的FMDV进行攻击,观察其保护效果。结果这2种重组疫苗均能诱导豚鼠产生特异性的体液免疫及细胞免疫应答。其中以pVRI-OAT/vUTA2-OAT的联合免疫方式的效果最好,其诱导的抗体水平接近于常规灭活疫苗,而细胞免疫水平则比后者高得多。攻击保护结果显示3个重组疫苗组均有一定保护效果,完全保护率和部分保护率分别为1/4和2/4。而PBS对照组发病率为4/4。结论证实了这2种重组疫苗在豚鼠体内具有良好的免疫原性。上述研究结果为FMDV基因工程疫苗的研究奠定了基础。     

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。     

白细胞介素2作为佐剂增强乙型肝炎病毒基因疫苗诱导的免疫应答

目的 :构建乙型肝炎病毒 (HBV)基因疫苗 pCR3.1 S ,观察重组人白细胞介素 2 (rhIL 2 )作为佐剂对其诱导BALB/c小鼠产生免疫应答的影响。方法 :以ELISA法检测免疫小鼠血清抗HBs抗体 ,另用3 H TdR掺入法测定淋巴细胞增殖活性 ,初步研究不同组的体液和细胞免疫应答。结果 :rhIL 2组免疫小鼠抗HBs抗体和淋巴细胞增殖活性与对照组比较差异有统计学意义 (P <0 .0 5 )。结论 :HBV基因疫苗可诱发BALB/c小鼠产生良好的免疫应答 ,rhIL 2作为佐剂可增强其免疫效应。     

表达高致病性PRRSV GP3和GP5基因的核酸疫苗构建及小鼠免疫效果评价

目的构建针对美洲型蓝耳病病毒的重组核酸疫苗,评价其与5种佐剂联合免疫BALB/C小鼠的效果。方法构建含有美洲型蓝耳病病毒GP3基因和GP5基因以及CpG-佐剂序列的重组核酸疫苗pVAX-N35HP,分别加入A1佐剂、A2佐剂、A3佐剂、A4佐剂和A8佐剂,免疫BALB/C小鼠,通过中和性抗体、T淋巴细胞亚群及细胞因子检测分析免疫效果。结果成功构建重组核酸质粒pVAX-N35-HP。用重组核酸质粒转染BHK-21细胞,Western blot显示重组核酸质粒稳定表达目的蛋白。中和性抗体结果显示,重组核酸疫苗免疫后35d,pVAX-N35HP+A1组和pVAXN35HP+A2组抗体滴度为1∶12;pVAX-N35HP+A3组抗体滴度为1∶16。pVAX-N35HP组细胞因子IL-4含量为阴性对照组的1.39倍,CD4+T淋巴细胞亚群百分率为阴性对照组的2.35倍(P0.01)。重组核酸质粒分别与5种佐剂联合免疫小鼠,pVAX-N35HP+A1组CD8+T淋巴细胞亚群百分率为pVAX-N35HP组的1.93倍;pVAX-N35HP+A3组免疫细胞因子IL-4为pVAX-N35HP组的1.41倍(P0.05),IFN-γ为pVAX-N35HP组的3.79倍(P0.01);pVAX-N35HP+A2、pVAX-N35HP+A4和pVAX-N35HP+A8组IFN-γ水平升高,CD8+T淋巴细胞数量增多。结论成功构建重组核酸疫苗pVAX-N35HP。该疫苗具有良好的免疫原性,其中A1、A3免疫佐剂的加入可增强小鼠细胞免疫和体液免疫水平。     

HIV-1中和抗体的作用与机制及实验室检测进展

人类免疫缺陷病毒Ⅰ型(HIV-1)中和抗体在防止病毒感染方面起到重要作用.最近的研究表明,中和抗体也能协同细胞免疫应答延缓感染者的疾病进程.HIV-1中和抗体主要通过结合HIV-1感染细胞过程中暴露的各种中间结构而干扰HIV-1进入靶细胞,从而阻断感染的发生.同时,病毒通过变异和外膜糖蛋白(Env)的高度糖基化发生免疫逃逸.目前中和抗体的检测主要依赖于体外中和试验,近年来研究者不断对该试验方案进行优化和标准化.对中和抗体作用的相关机制的逐渐阐明、相关检测技术的发展,必将推进疫苗研究的发展,并为疫苗评价提供新的可信的实验依据.     

HIV-1env/IFNα-2b表达产物诱导的淋巴细胞转化与CTL实验

目的　将艾滋病病毒外膜蛋白与干扰素 (HIV - 1env/IFNα - 2b)融合基因表达的融合蛋白 ,作为免疫原免疫小鼠 ,观察小鼠的免疫功能状态和细胞免疫应答。方法　将IFNα - 2b基因片段插入到env基因的nt8383位点 ,经脂质体转染与血凝素阴性蚀斑筛选 ,挑出重组痘苗病毒。经SDS -PAGE和Westernblot鉴定表达产物。以小鼠为实验对象 ,用重组痘苗病毒vJ16env/IFNα - 2b免疫小鼠 ,以生理盐水和野生型痘苗病毒为对照 ,用MTT法和 3H -TdR掺入法动态检测小鼠脾淋巴细胞对ConA、Lps的反应性与CTL杀伤活性。结果　脾淋巴细胞对ConA、Lps刺激指数与CTL的杀伤活性百分率 ,其实验组与对照组比较差异有显著性意义 (P <0 0 5 )。ConA、Lps刺激指数实验组间比较差异有显著意义 (P <0 0 5 )。结论　重组痘苗病毒vJ16env/IFNα - 2b能增强小鼠脾淋巴细胞的保护性细胞免疫。IFNα - 2b能作为免疫佐剂加强env蛋白的免疫原性 ,提高免疫小鼠的T淋巴细胞免疫能力。     

应用不同表达载体表达欧洲型PRRSVORF5蛋白的研究

目的构建多种欧洲型PRRSVGP5蛋白原核表达载体,并比较其在大肠埃希菌中的表达效率。方法参考GenBank发表的欧洲型PRRSVLV株（GenBank登录号：M96262）ORF5序列,通过序列分析,设计合成ORF5全基因序列扩增引物及信号肽缺失引物。构建原核表达质粒pET-28a—GP5、pET-28a—gGP5、pET-22b—GP5、pET-22b—gGP5、pET-32a—GP5、pET-32a—gGP5、pGEX-4T—GP5、pGEX-4T—gGP5,经IPTG诱导后采用SDS—PAGE电泳分析GP5蛋白在各个原核表达载体的表达情况。结果pET-28a—gGP5、pET-22b—gGP5、pET-32a—gGP5均没有高效的表达出缺失信号肽的GP5蛋白,缺少信号肽的GP5蛋白在pGEX-4T-1载体中高效表达,目的蛋白分子质量单位为42ku,与理论值相符。没有缺失信号肽的GP5蛋白在pET-28a—GP5、pET22b—GP5、pET-32a—GP5、pGEX-4T—GP5,均未得到高效表达。结论本实验构建的重组原核表达载体pGEX-4T—gGP5能在大肠埃希菌中高效表达欧洲型PRRSVGP5蛋白,为进一步分析该蛋白的抗原性奠定了基础。     

Comparison of HIV Type 1 ADA gp120 monomers versus gp140 trimers as immunogens for the induction of neutralizing antibodies

Designing an immunogen for effective neutralizing antibody induction against diverse primary isolates of human immunodeficiency virus type 1 (HIV-1) is a high priority for HIV-1 vaccine development. Soluble gp120 envelope (Env) glycoprotein subunit vaccines elicit high titers of antibodies that neutralize T cell line-adapted (TCLA) strains but the antibodies possess poor neutralizing activity against many primary isolates. Previously, we generated soluble trimeric recombinant gp140 from the HIV-1 primary isolate ADA. Here we compared monomeric ADAgp120 and trimeric ADAgp140 as immunogens for neutralizing antibody responses in guinea pigs. Both immunogens generated a neutralizing antibody response that was detectable against the vaccine strain and several heterologous strains. The magnitude of this response was significantly greater in ADAgp140-immunized animals when measured against the TCLA strain, MN, and the R5 primary isolate, Bal. Two additional isolates (SS1196 and Bx08) were neutralized equally by sera from both groups of animals whereas other isolates were neutralized weakly or not at all. Despite equal titers of V3 loop specific binding antibodies in sera from both groups of animals, neutralization of ADA by sera from gp140-immunized animals was insensitive to the presence of ADA-V3 peptide, whereas addition of this peptide to sera from gp120- immunized animals blocked all detectable neutralizing activity against ADA. These results support the idea that trimeric gp140 is an improved immunogen compared to monomeric gp120 but that additional improvements are required to afford broad protection against a spectrum of heterologous primary HIV-1 isolates. This ADAgp140 immunogen may be considered a starting point from which to engineer additional improvements for cross-reactive neutralizing antibody induction.     

Synergistic Pathogenicity by Coinfection and Sequential Infection with NADC30-like PRRSV and PCV2 in Post-Weaned Pigs

Porcine reproductive and respiratory syndrome virus (PRRSV) and porcine circovirus (PCVs) are two major viruses that affect pigs. Coinfections between PRRSV and PCV2 are frequently reported in most outbreaks, with clinical presentations involving dyspnea, fever, reduced feed intake, weight loss, and death in fattening pigs. The NADC30-like PRRSV and PCV2d are the main circulating virus strains found in China. This study determines the impact of NADC30-like PRRSV and PCV2d mono-infection and coinfection on the immune system, organ pathology, and viral shedding in five-week-old post-weaned pigs. Pigs were randomly divided into six groups: PBS, PRRSV, PCV2, PRRSV-PCV2 coinfection (co), and PRRSV-PCV2 or PCV2-PRRSV sequential infections. Fever, dyspnea, decreased feed intake, weight loss, and pig deaths occurred in groups infected with PRRSV, Co-PRRSV-PCV2, and PRRSV-PCV2. The viral load was higher in Co-PRRSV-PCV2, PRRSV-PCV2, and PCV2-PRRSV than those mono-infected with PRRSV or PCV2. Additionally, cytokines (IFN-γ, TNF-α, IL-4, and IL-10) produced by pigs under Co-PRRSV-PCV2 and PRRSV-PCV2 groups were more intense than the other groups. Necropsy findings showed hemorrhage, emphysema, and pulmonary adhesions in the lungs of pigs infected with PRRSV. Smaller alveoli and widened lung interstitium were found in the Co-PRRSV-PCV2 and PRRSV-PCV2 groups. In conclusion, PRRSV and PCV2 coinfection and sequential infection significantly increased viral pathogenicity and cytokine responses, resulting in severe clinical signs, lung pathology, and death.     

Nasal immunization with a recombinant HIV gp120 and nanoemulsion adjuvant produces Th1 polarized responses and neutralizing antibodies to primary HIV type 1 isolates

Epidemiological and experimental data suggest that both robust neutralizing antibodies and potent cellular responses play important roles in controlling primary HIV-1 infection. In this study we have investigated the induction of systemic and mucosal immune responses to HIV gp120 monomer immunogen administered intranasally in a novel, oil-in-water nanoemulsion (NE) adjuvant. Mice and guinea pigs intranasally immunized by the application of recombinant HIV gp120 antigen mixed in NE demonstrated robust serum anti-gp120 IgG, as well as bronchial, vaginal, and serum anti-gp120 IgA in mice. The serum of these animals demonstrated antibodies that cross-reacted with heterologous serotypes of gp120 and had significant neutralizing activity against two clade-B laboratory strains of HIV (HIVBaL and HIVSF162) and five primary HIV-1 isolates. The analysis of gp120-specific CTL proliferation, INF-gamma induction, and prevalence of anti-gp120 IgG2 subclass antibodies indicated that nasal vaccination in NE also induced systemic, Th1-polarized cellular immune responses. This study suggests that NE should be evaluated as a mucosal adjuvant for multivalent HIV vaccines.     

Protection against Mucosal SHIV Challenge by Peptide and Helper-Dependent Adenovirus Vaccines

Groups of rhesus macaques that had previously been immunized with HIV-1 envelope (env) peptides and first generation adenovirus serotype 5 (FG-Ad5) vaccines expressing the same peptides were immunized intramuscularly three times with helper-dependent adenovirus (HD-Ad) vaccines expressing only the HIV-1 envelope from JRFL. No gag, pol, or other SHIV genes were used for vaccination. One group of the FG-Ad5-immune animals was immunized three times with HD-Ad5 expressing env. One group was immunized by serotype-switching with HD-Ad6, HD-Ad1, and HD-Ad2 expressing env. Previous work demonstrated that serum antibody levels against env were significantly higher in the serotype-switched group than in the HD-Ad5 group. In this study, neutralizing antibody and T cell responses were compared between the groups before and after rectal challenge with CCR5-tropic SHIV-SF162P3. When serum samples were assayed for neutralizing antibodies, only weak activity was observed. T cell responses against env epitopes were higher in the serotype-switched group. When these animals were challenged rectally with SHIV-SF162P3, both the Ad5 and serotype-switch groups significantly reduced peak viral loads 2 to 10-fold 2 weeks after infection. Peak viral loads were significantly lower for the serotype-switched group as compared to the HD-Ad5-immunized group. Viral loads declined over 18 weeks after infection with some animals viremia reducing nearly 4 logs from the peak. These data demonstrate significant mucosal vaccine effects after immunization with only env antigens. These data also demonstrate HD-Ad vectors are a robust platform for vaccination.     

Harnessing the Genetic Plasticity of Porcine Circovirus Type 2 to Target Suicidal Replication

Porcine circovirus type 2 (PCV2), the causative agent of a wasting disease in weanling piglets, has periodically evolved into several new subtypes since its discovery, indicating that the efficacy of current vaccines can be improved. Although a DNA virus, the mutation rates of PCV2 resemble RNA viruses. The hypothesis that recoding of selected serine and leucine codons in the PCV2b capsid gene could result in stop codons due to mutations occurring during viral replication and thus result in rapid attenuation was tested. Vaccination of weanling pigs with the suicidal vaccine constructs elicited strong virus-neutralizing antibody responses. Vaccination prevented lesions, body-weight loss, and viral replication on challenge with a heterologous PCV2d strain. The suicidal PCV2 vaccine construct was not detectable in the sera of vaccinated pigs at 14 days post-vaccination, indicating that the attenuated vaccine was very safe. Exposure of the modified virus to immune selection pressure with sub-neutralizing levels of antibodies resulted in 5 of the 22 target codons mutating to a stop signal. Thus, the described approach for the rapid attenuation of PCV2 was both effective and safe. It can be readily adapted to newly emerging viruses with high mutation rates to meet the current need for improved platforms for rapid-response vaccines.     

Protective antibody responses elicited by a meningococcal outer membrane vesicle vaccine with overexpressed genome-derived neisserial antigen 1870

Background. Meningococcal outer membrane vesicle (OMV) vaccines are efficacious in humans but have serosubtype-specific serum bactericidal antibody responses directed at the porin protein PorA and the potential for immune selection of PorA-escape mutants.Methods. We prepared an OMV vaccine from a Neisseria meningitidis strain engineered to overexpress genome-derived neisserial antigen (GNA) 1870, a lipoprotein discovered by genome mining that is being investigated for use in a vaccine.Results. Mice immunized with the modified GNA1870-OMV vaccine developed broader serum bactericidal antibody responses than control mice immunized with a recombinant GNA1870 protein vaccine or an OMV vaccine prepared from wild-type N. meningitidis or a combination of vaccines prepared from wild-type N. meningitidis and recombinant protein. Antiserum from mice immunized with the modified GNA1870-OMV vaccine also elicited greater deposition of human C3 complement on the surface of live N. meningitidis bacteria and greater passive protective activity against meningococcal bacteremia in infant rats. A N. meningitidis mutant with decreased expression of PorA was more susceptible to bactericidal activity of anti-GNA1870 antibodies.Conclusions. The modified GNA1870-OMV vaccine elicits broader protection against meningococcal disease than recombinant GNA1870 protein or conventional OMV vaccines and also has less risk of selection of PorA-escape mutants than a conventional OMV vaccine.     

Elicitation of Neutralizing Antibody Responses to HIV-1 Immunization with Nanoparticle Vaccine Platforms

A leading strategy for developing a prophylactic HIV-1 vaccine is the elicitation of antibodies that can neutralize a large fraction of circulating HIV-1 variants. However, a major challenge that has limited the effectiveness of current vaccine candidates is the extensive global diversity of the HIV-1 envelope protein (Env), the sole target for HIV-neutralizing antibodies. To address this challenge, various strategies incorporating Env diversity into the vaccine formulation have been proposed. Here, we assessed the potential of two such strategies that utilize a nanoparticle-based vaccine platform to elicit broadly neutralizing antibody responses. The nanoparticle immunogens developed here consisted of different formulations of Envs from strains BG505 (clade A) and CZA97 (clade C), attached to the N-termini of bacterial ferritin. Single—antigen nanoparticle cocktails, as well as mosaic nanoparticles bearing both Env trimers, elicited high antibody titers in mice and guinea pigs. Furthermore, serum from guinea pigs immunized with nanoparticle immunogens achieved autologous, and in some cases heterologous, tier 2 neutralization, although significant differences between mosaic and single—antigen nanoparticles were not observed. These results provide insights into the ability of different vaccine strategies for incorporating Env sequence diversity to elicit neutralizing antibodies, with implications for the development of broadly protective HIV-1 vaccines.     

弓形虫SAG1单基因疫苗与SAG1-ROP2复合基因疫苗的免疫效果观察

目的构建弓形虫主要表面抗原SAG1单价基因疫苗及其与棒状体蛋白ROP2的复合基因疫苗,接种BALB/c小鼠,观察疫苗的免疫保护性。方法构建重组质粒pcDNA3.1SAG1及pcDNA3.1SAG1ROP2。将两核酸疫苗分别免疫小鼠,ELISA法检测血清IgG抗体、IFNγ、IL4;流式细胞仪测定T细胞亚群;弓形虫速殖子腹腔攻击感染观察小鼠生存时间。结果获得pcDNA3.1SAG1、pcDNA3.1SAG1ROP2重组质粒;pcDNA3.1SAG1ROP2组小鼠IgG抗体(P<0.05)、IFNγ(P<0.01)及CD8+细胞比例(P<0.05)均高于pcDNA3.1SAG1组;实验组组均未测到IL4;复合基因组感染弓形虫后生存时间较单基因组延长(P<0.01)。结论弓形虫不同生活阶段的抗原基因复合疫苗较单基因疫苗具有更好的免疫保护性。