Cross-protection

交叉保护
  • 文章类型: Journal Article
    冷冻面团技术在现代面包店操作中很重要,便于将低温面团运输到下游销售点。然而,冻融过程给面包师的酵母带来了巨大的压力,导致生存能力和发酵能力下降。了解冻融胁迫的潜在机制对于减轻其对酵母性能的不利影响至关重要。这篇综述深入研究了冻融应力的复杂机制,特别关注酿酒酵母,烘焙中使用的主要酵母,并提出了广泛的生物技术方法来提高酿酒酵母的抗冻融性。策略包括操纵细胞内代谢物,改变膜组成,管理抗氧化防御,介导水通道蛋白表达,并采用适应性进化和育种技术。应对与冻融压力相关的挑战和策略,这篇综述为未来的研究工作提供了宝贵的见解,旨在提高面包酵母的冻融耐受性,为面包店科学的发展做出贡献。
    Frozen dough technology is important in modern bakery operations, facilitating the transportation of dough at low temperatures to downstream sales points. However, the freeze-thaw process imposes significant stress on baker\'s yeast, resulting in diminished viability and fermentation capacity. Understanding the mechanisms underlying freeze-thaw stress is essential for mitigating its adverse effects on yeast performance. This review delves into the intricate mechanisms underlying freeze-thaw stress, focusing specifically on Saccharomyces cerevisiae, the primary yeast used in baking, and presents a wide range of biotechnological approaches to enhance freeze-thaw resistance in S. cerevisiae. Strategies include manipulating intracellular metabolites, altering membrane composition, managing antioxidant defenses, mediating aquaporin expression, and employing adaptive evolutionary and breeding techniques. Addressing challenges and strategies associated with freeze-thaw stress, this review provides valuable insights for future research endeavors, aiming to enhance the freeze-thaw tolerance of baker\'s yeast and contribute to the advancement of bakery science.
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  • 文章类型: Journal Article
    背景:二价人乳头瘤病毒HPV16/18-AS04疫苗(Cervarix,GSK)提供针对HPV16/18的直接保护。随机对照试验的结果显示了交叉保护作用,并表明在疫苗接种覆盖率高的人群中,一些密切相关的HPV类型可能会下降。
    目的:为了评估英格兰实施后监测中HPV16/18-AS04提供的交叉保护的证据,以及这如何补充其他国家的临床试验数据和实施后观察。
    方法:从英格兰的HPV监测中收集了接受HPV16/18-AS04疫苗接种的年轻女性交叉保护的证据。对临床试验和其他实施后研究的数据进行了审查。
    结果:在英格兰使用匿名残留标本进行的监测发现下降了52.3%,在16-18岁、19-21岁和22-24岁人群中,HPV-31/33/45分组为67.4%和33.3%,分别。此外,类型特异性分析发现,在所有年龄组中,HPV31的患病率均下降至1%以下.自引入疫苗接种计划以来,交叉保护一直受到监测和维持超过10年。在英国监测结果中未发现针对HPV6/11的交叉保护。
    结论:对英格兰符合疫苗资格的人群中特定类型感染的监测已经产生了明确的证据,表明HPV16/18-AS04疫苗接种对高危HPV31/33/45感染具有交叉保护作用。与其他实施后的观察结果一致,并确认并在某些方面超出了临床试验的预期。
    BACKGROUND: Bivalent human papillomavirus HPV16/18-AS04 vaccine (Cervarix, GSK) offers direct protection against HPV16/18. Results from randomised controlled trials showed cross protective effects and suggested that declines in some closely related HPV types could be expected in a population with high vaccination coverage.
    OBJECTIVE: To evaluate the evidence for cross-protection afforded by HPV16/18-AS04 from post-implementation surveillance in England, and how this complements clinical trial data and post-implementation observations in other countries.
    METHODS: Evidence of cross-protection in young women offered vaccination with HPV16/18-AS04 was gathered from HPV surveillance in England. Data from clinical trials and other post-implementation studies were reviewed.
    RESULTS: Surveillance using anonymised residual specimens in England found declines of 52.3%, 67.4% and 33.3% against grouped HPV-31/33/45 in 16-18, 19-21, and 22-24 year olds, respectively. Additionally, type-specific analysis found that the prevalence of HPV31 declined to below 1% across all age groups. Cross-protection has been monitored and maintained for over 10 years since the introduction of the vaccination programme. Cross-protection against HPV6/11 was not found in English surveillance outcomes.
    CONCLUSIONS: Surveillance of type-specific infections in vaccine-eligible populations in England has generated clear evidence of cross-protective effects from HPV16/18-AS04 vaccination against high-risk HPV 31/33/45 infections, consistent with other post-implementation observations and confirming and in some ways exceeding expectations from clinical trials.
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  • 文章类型: Journal Article
    东亚西番莲病毒(EAPV)引起西番莲木屑病,限制东亚西番莲生产的主要威胁,包括台湾和越南。在这项研究中,用绿色荧光蛋白(GFP)报告基因标记台湾严重分离株EAPV-TW的感染性cDNA克隆,以监测植物中的病毒。接种了该构建体的烟草本氏和黄色西番莲植物显示出EAPV-TW的典型症状。基于我们以前对马铃薯病毒HC-Pro的致病性决定因素的研究,仅六个氨基酸的缺失(d6)及其与点突变的关联(F8I,简化为I8)在EAPV-TW的HC-Pro基因的N末端区域进行,分别产生EAPV-d6和EAPV-d6I8的突变体。突变型EAPV-d6I8引起的感染在N.benthamiana和黄色西番莲植物中没有明显的症状,而EAPV-d6仍然诱导轻微的叶片斑点。EAPV-d6I8在温室条件下经过6次传代后是稳定的,并显示出病毒积累的之字形模式,典型的有益保护性病毒。EAPV-d6I8的交叉保护有效性在温室条件下在N.benthamiana和黄色西番莲植物中进行了评估。EAPV-d6I8在N.benthamiana和黄色西番莲植物中对野生型EAPV-TW-GFP赋予了完全的交叉保护(100%),经证实没有严重症状,没有荧光信号,和GFP的PCR阴性状态。此外,EAPV-d6I8还对黄色西番莲植物中的越南严重菌株EAPV-GL1提供了完全保护。我们的结果表明,减毒突变体EAPV-d6I8具有通过交叉保护在台湾和越南控制EAPV的巨大潜力。
    East Asian Passiflora virus (EAPV) causes passionfruit woodiness disease, a major threat limiting passionfruit production in eastern Asia, including Taiwan and Vietnam. In this study, an infectious cDNA clone of a Taiwanese severe isolate EAPV-TW was tagged with a green fluorescent protein (GFP) reporter to monitor the virus in plants. Nicotiana benthamiana and yellow passionfruit plants inoculated with the construct showed typical symptoms of EAPV-TW. Based on our previous studies on pathogenicity determinants of potyviral HC-Pros, a deletion of six amino acids (d6) alone and its association with a point mutation (F8I, simplified as I8) were conducted in the N-terminal region of the HC-Pro gene of EAPV-TW to generate mutants of EAPV-d6 and EAPV-d6I8, respectively. The mutant EAPV-d6I8 caused infection without conspicuous symptoms in N. benthamiana and yellow passionfruit plants, while EAPV-d6 still induced slight leaf mottling. EAPV-d6I8 was stable after six passages under greenhouse conditions and displayed a zigzag pattern of virus accumulation, typical of a beneficial protective virus. The cross-protection effectiveness of EAPV-d6I8 was evaluated in both N. benthamiana and yellow passionfruit plants under greenhouse conditions. EAPV-d6I8 conferred complete cross-protection (100%) against the wild-type EAPV-TW-GFP in both N. benthamiana and yellow passionfruit plants, as verified by no severe symptoms, no fluorescent signals, and PCR-negative status for GFP. Furthermore, EAPV-d6I8 also provided complete protection against Vietnam\'s severe strain EAPV-GL1 in yellow passionfruit plants. Our results indicate that the attenuated mutant EAPV-d6I8 has great potential to control EAPV in Taiwan and Vietnam via cross-protection.
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  • 文章类型: Journal Article
    大多数冠状病毒疫苗专注于尖峰(S)抗原,但S的频繁突变引发了人们对疫苗对抗新变种的效力的担忧.尽管已经测试了具有保守序列的其他抗原,这些疫苗在多大程度上可以提供针对不同冠状病毒物种的免疫力,目前尚不清楚。在这项研究中,我们评估了核衣壳(N)作为冠状病毒疫苗抗原的潜力.用MERS-CoVN免疫诱导强烈的免疫反应,对MERS-CoV提供显著保护。值得注意的是,MERS-CoVN引发对SARS-CoV-2N的交叉反应性T细胞反应,并在短暂的hACE2小鼠模型中对SARS-CoV-2攻击后显着减少肺部炎症。然而,在K18-hACE转基因小鼠中,疫苗显示出有限的保护。总的来说,我们的研究结果表明,冠状病毒N可以是一种有效的疫苗抗原,对抗同源病毒,但是它的功效可能因不同的冠状病毒而异,强调需要进一步研究使用保守抗原的泛冠状病毒疫苗。
    Most coronavirus vaccines focus on the spike (S) antigen, but the frequent mutations in S raise concerns about the vaccine efficacy against new variants. Although additional antigens with conserved sequences are have been tested, the extent to which these vaccines can provide immunity against different coronavirus species remains unclear. In this study, we assessed the potential of nucleocapsid (N) as a coronavirus vaccine antigen. Immunization with MERS-CoV N induced robust immune responses, providing significant protection against MERS-CoV. Notably, MERS-CoV N elicited cross-reactive T cell responses to SARS-CoV-2 N and significantly reduced lung inflammation following a SARS-CoV-2 challenge in the transient hACE2 mouse model. However, in K18-hACE transgenic mice, the vaccine showed limited protection. Collectively, our findings suggest that coronavirus N can be an effective vaccine antigen against homologous viruses, but its efficacy may vary across different coronaviruses, highlighting the need for further research on pan-coronavirus vaccines using conserved antigens.
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  • 文章类型: Journal Article
    禽致病性大肠杆菌(APEC)是一种著名的病原体,经常导致禽大肠杆菌病,对家禽业和公众健康都构成重大风险。针对禽大肠杆菌病的商业疫苗主要是灭活疫苗,但它们的有效性仅限于特定的血清型。最近的进展突出了细菌膜囊泡(MV)作为疫苗研究中的有希望的候选者。如何大规模生产细菌MV疫苗是MV产业化的重大挑战。msbB基因编码酰基转移酶,并参与改变脂质A的酰化模式,导致脂多糖(LPS)中脂质A含量降低。这里,我们评估了来自LPS低表达APEC菌株FY26ΔmsbB的MV的免疫保护功效,这是一个带有msbB基因缺失的APEC突变株。采用氮气空化技术提取APECMV,结果表明,与自然培养相比,MV产量显着增加。评估了免疫效果,揭示FY26ΔmsbBMV引起蛋鸡的抗体反应并促进细菌清除。保护效力研究表明,用FY26ΔmsbBMV免疫在用野生型APEC菌株FY26攻击的鸡中赋予免疫保护。值得注意的是,从突变体FY26ΔmsbB回收的LPS低携带MV也显示出交叉保护能力,并有效预防由O1,O7,O45,O78和O101血清型毒力APEC菌株引起的感染。这些发现表明,由LPS低表达的APEC菌株FY26ΔmsbB产生的MV代表了一种新颖的,经过经验验证的亚单位疫苗,可用于预防和控制各种APEC血清型的感染。
    Avian pathogenic Escherichia coli (APEC) is a notable pathogen that frequently leads to avian colibacillosis, posing a substantial risk to both the poultry industry and public health. The commercial vaccines against avian colibacillosis are primarily inactivated vaccines, but their effectiveness is limited to specific serotypes. Recent advances have highlighted bacterial membrane vesicles (MV) as a promising candidate in vaccine research. How to produce bacterial MVs vaccines on a large scale is a significant challenge for the industrialization of MVs. The msbB gene encodes an acyltransferase and has been implicated in altering the acylation pattern of lipid A, leading to a decrease in lipid A content in lipopolysaccharides (LPS). Here, we evaluated the immunoprotective efficacy of MVs derived from the LPS low-expressed APEC strain FY26ΔmsbB, which was an APEC mutant strain with a deletion of the msbB gene. The nitrogen cavitation technique was employed to extract APEC MVs, with results indicating a significant increase in MVs yield compared to that obtained under natural culture. The immunization effectiveness was assessed, revealing that FY26ΔmsbB MVs elicited an antibody response of laying hens and facilitated bacterial clearance. Protective efficacy studies demonstrated that immunization with FY26ΔmsbB MVs conferred the immune protection in chickens challenged with the wild-type APEC strain FY26. Notably, LPS low-carried MVs recovered from the mutant FY26ΔmsbB also displayed cross-protective capabilities, and effectively safeguarding against infections caused by O1, O7, O45, O78, and O101 serotypes virulent APEC strains. These findings suggest that MVs generated from the LPS low-expressed APEC strain FY26ΔmsbB represent a novel and empirically validated subunit vaccine for the prevention and control of infections by various APEC serotypes.
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  • 文章类型: Journal Article
    流感病毒感染对公众健康构成持续威胁。这里,我们开发了可溶性三聚体HA胞外域疫苗,通过在茎区建立间二硫键,有效保留茎表位的天然抗原性。与未修饰的HA相比,稳定的三聚体H1胞外域蛋白表现出更高的热稳定性,并且对一组识别蛋白间或蛋白内表位的抗茎交叉反应性抗体显示出强结合活性。阴性染色透射电子显微镜(TEM)分析显示,蛋白质间二硫键钉合WA11#5,NC99#2和FLD#1蛋白的稳定三聚体结构以及未修饰的HA分子的不规则聚集。与未修饰的HA蛋白相比,用那些用不完全弗氏佐剂配制的三聚体HA胞外域疫苗对小鼠的免疫引发了显著更有效的交叉中和抗体应答,并提供了针对异源流感病毒株的致死性感染的更广泛的免疫保护。此外,我们的研究结果表明,HA茎特异性抗体应答水平升高与交叉保护增强相关.我们的设计策略已被证明有效的三聚HA胞外域衍生自甲型和乙型流感病毒,从而为今后设计流感HA免疫原提供有价值的参考。
    Influenza virus infection poses a continual menace to public health. Here, we developed soluble trimeric HA ectodomain vaccines by establishing interprotomer disulfide bonds in the stem region, which effectively preserve the native antigenicity of stem epitopes. The stable trimeric H1 ectodomain proteins exhibited higher thermal stabilities in comparison with unmodified HAs and showed strong binding activities towards a panel of anti-stem cross-reactive antibodies that recognize either interprotomer or intraprotomer epitopes. Negative stain transmission electron microscopy (TEM) analysis revealed the stable trimer architecture of the interprotomer disulfide-stapled WA11#5, NC99#2, and FLD#1 proteins as well as the irregular aggregation of unmodified HA molecules. Immunizations of mice with those trimeric HA ectodomain vaccines formulated with incomplete Freund\'s adjuvant elicited significantly more potent cross-neutralizing antibody responses and offered broader immuno-protection against lethal infections with heterologous influenza strains compared to unmodified HA proteins. Additionally, the findings of our study indicate that elevated levels of HA stem-specific antibody responses correlate with strengthened cross-protections. Our design strategy has proven effective in trimerizing HA ectodomains derived from both influenza A and B viruses, thereby providing a valuable reference for designing future influenza HA immunogens.
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  • 文章类型: Journal Article
    流感季节每年都会出现,建立个体的免疫史,但这一病史对后续流感疫苗保护的影响尚不清楚.我们从动物试验中提取数据以研究其潜在影响。试验涉及80只雪貂,每个人在接种疫苗前接受一种类型的感染或安慰剂。我们通过评估血凝抑制(HAI)抗体效价应答来定量疫苗保护。我们测试了具有不同感染史的宿主在接受相同疫苗时对于所有同源和异源结果是否表现出相似水平的应答。我们观察到,不同的预先存在的免疫通常有利于疫苗诱导的反应,但幅度不同。没有预先豁免权,第1剂疫苗接种后的HAI滴度较不可能超过1:40,因此需要加强注射.我们的研究表明,预先存在的免疫可能会增强和延长同源和异源疫苗反应。
    Influenza seasons occur annually, building immune history for individuals, but the influence of this history on subsequent influenza vaccine protection remains unclear. We extracted data from an animal trial to study its potential impact. The trial involved 80 ferrets, each receiving either one type of infection or a placebo before vaccination. We quantified the vaccine protection by evaluating hemagglutination inhibition (HAI) antibody titer responses. We tested whether hosts with different infection histories exhibited similar level of responses when receiving the same vaccine for all homologous and heterologous outcomes. We observed that different pre-existing immunities were generally beneficial to vaccine induced responses, but varied in magnitude. Without pre-immunity, post-vaccination HAI titers after the 1st dose of the vaccine were less likely to be above 1:40, and a booster shot was needed. Our study suggests that pre-existing immunity may strengthen and extend the homologous and heterologous vaccine responses.
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  • 文章类型: Journal Article
    目前批准临床使用的流感疫苗主要包括流感病毒灭活疫苗和流感减毒活疫苗(LAIV)。LAIV有多重优势,如易用性和强免疫原性,可以提供交叉保护。在这项研究中,PR8病毒的M基因突变如下(G11T,C79G,G82C,C85G,andC1016A),用反向基因技术解救并获得含有突变M基因的减毒流感病毒作为疫苗候选物。在MDCK细胞和毒力减弱的小鼠中,被拯救病毒的复制能力均显着减弱。对免疫原性的研究发现,1000TCID50的突变型PR8(mPR8)可以引发强烈的体液和细胞免疫应答。1000TCID50mPR8的单剂量免疫不仅能够对抗同源PR8病毒的攻击,而且还提供针对异源H9N2病毒的交叉保护。
    The influenza vaccines currently approved for clinical use mainly include inactivated influenza virus vaccines and live attenuated influenza vaccines (LAIVs). LAIVs have multiple advantages, such as ease of use and strong immunogenicity, and can provide cross-protection. In this study, the M gene of the PR8 virus was mutated as follows (G11T, C79G, G82C, C85G, and C1016A), and a live attenuated influenza virus containing the mutated M gene was rescued and obtained using reverse genetic technology as a vaccine candidate. The replication ability of the rescued virus was significantly weakened in both MDCK cells and mice with attenuated virulence. Studies on immunogenicity found that 1000 TCID50 of mutated PR8 (mPR8) can prime strong humoral and cellular immune responses. Single-dose immunization of 1000 TCID50 mPR8 was not only able to counter the challenge of the homologous PR8 virus but also provided cross-protection against the heterologous H9N2 virus.
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  • 文章类型: Journal Article
    4组分脑膜炎球菌血清群B(MenB)疫苗,4CMenB,第一个广泛保护性的,基于蛋白质的MenB疫苗将获得许可,现已在全球50多个国家注册。过去十年的真实世界证据(RWE)证实了它的有效性和影响,婴儿免疫计划显示,针对侵袭性MenB疾病的疫苗效力为71-95%,并且对非B血清群具有交叉保护作用,包括在英格兰符合4CMenB标准的队列中,血清群W病例减少了69%。来自不同国家的RWE也证明了在青少年中额外适度保护淋病的潜力。4CMenB的实际安全性与许可前报告一致。使用针对110种MenB菌株的内源性补体人血清杀菌抗体(enc-hSBA)测定可以评估多组分MenB疫苗在临床试验环境中的免疫学有效性。需要公平获得4CMenB疫苗接种,以更好地保护所有年龄组,包括老年人,通过综合免疫政策和弱势群体。
    侵袭性脑膜炎球菌病,由脑膜炎奈瑟菌(脑膜炎球菌)引起,是罕见的,但往往是毁灭性的,可能是致命的。有有效的疫苗,包括针对脑膜炎球菌血清群B疾病的疫苗。2013年,4组分脑膜炎球菌血清群B疫苗,4CMenB,成为第一个广泛保护的,基于蛋白质的针对血清群B的疫苗将获得许可,第二种(二价疫苗,MenB-FHbp)第二年获得许可。4CMenB现已在50多个国家注册,在大多数情况下,适用于婴儿和所有年龄组。在美国,它适用于10-25岁的个人。过去十年免疫计划的证据,比较接种疫苗和未接种疫苗的个体以及接种疫苗前后的相同人群,证实了4CMenB对血清群B疾病的有效性和积极影响。这也证明4CMenB可以提供针对由其他脑膜炎球菌血清群引起的侵袭性疾病的保护。此外,脑膜炎奈瑟菌与引起淋病的细菌密切相关,淋病奈瑟菌,和新兴的现实世界的证据表明,4CMenB提供额外的中度保护对淋球菌疾病。4CMenB给大量婴儿时的安全性,孩子们,青少年,成年人与许可前报告的4CMenB安全概况一致。为了未来,解决建议管理4CMenB的国家指南之间的差异将是有益的,特别是在有流行病学支持性证据但没有公平接种疫苗的情况下。还需要用于评估脑膜炎球菌血清群B疫苗在临床试验中的潜在有效性的新测定法,因为在人群中传播的血清群B菌株在不同国家之间非常多样化。
    The 4-component meningococcal serogroup B (MenB) vaccine, 4CMenB, the first broadly protective, protein-based MenB vaccine to be licensed, is now registered in more than 50 countries worldwide. Real-world evidence (RWE) from the last decade confirms its effectiveness and impact, with infant immunization programs showing vaccine effectiveness of 71-95% against invasive MenB disease and cross-protection against non-B serogroups, including a 69% decrease in serogroup W cases in 4CMenB-eligible cohorts in England. RWE from different countries also demonstrates the potential for additional moderate protection against gonorrhea in adolescents. The real-world safety profile of 4CMenB is consistent with prelicensure reports. Use of the endogenous complement human serum bactericidal antibody (enc-hSBA) assay against 110 MenB strains may enable assessment of the immunological effectiveness of multicomponent MenB vaccines in clinical trial settings. Equitable access to 4CMenB vaccination is required to better protect all age groups, including older adults, and vulnerable groups through comprehensive immunization policies.
    Invasive meningococcal disease, caused by the bacterium Neisseria meningitidis(meningococcus), is rare but often devastating and can be deadly. Effective vaccines are available, including vaccines against meningococcal serogroup B disease. In 2013, the 4-component meningococcal serogroup B vaccine, 4CMenB, became the first broadly protective, protein-based vaccine against serogroup B to be licensed, with the second (bivalent vaccine, MenB-FHbp) licensed the following year. 4CMenB is now registered in more than 50 countries, in the majority, for infants and all age groups. In the US, it is approved for individuals aged 10–25 years. Evidence from immunization programs in the last decade, comparing vaccinated and unvaccinated individuals and the same population before and after vaccination, confirms the effectiveness and positive impact of 4CMenB against serogroup B disease. This also demonstrates that 4CMenB can provide protection against invasive diseases caused by other meningococcal serogroups. Furthermore, N. meningitidis is closely related to the bacterium that causes gonorrhea, N. gonorrhoeae, and emerging real-world evidence suggests that 4CMenB provides additional moderate protection against gonococcal disease. The safety of 4CMenB when given to large numbers of infants, children, adolescents, and adults is consistent with the 4CMenB safety profile reported before licensure.For the future, it would be beneficial to address differences among national guidelines for the recommended administration of 4CMenB, particularly where there is supportive epidemiological evidence but no equitable access to vaccination. New assays for assessing the potential effectiveness of meningococcal serogroup B vaccines in clinical trials are also required because serogroup B strains circulating in the population are extremely diverse across different countries.
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  • 文章类型: Journal Article
    恢复期血浆已被证明可有效保护人类免受新世界(NW)沙粒病毒引起的严重疾病,包括Junin病毒(JUNV)和Machupo病毒(MACV)。该血浆含有针对包括由GP1和GP2组成的核衣壳和包膜糖蛋白(GPcs)的完整互补结构蛋白的抗体。为了深入了解抗GPc特异性多克隆抗体的保护和交叉保护特性,我们在Hartley豚鼠模型中评估了DNA疫苗产生的抗GPc兔抗血清靶向MACV株Carvallo的能力,以提供针对另一种称为Chicava的MACV株的异源保护.发现兔抗血清对异源MACV菌株Chicava和Mallale的中和活性降低了54倍和23倍,分别,与PRNT50测定中针对同源MACV菌株Carvallo的滴度进行比较。尽管对Chicava菌株的中和活性较低,兔抗血清保护100%的豚鼠从这种菌株时,给药长达4天感染后,而所有对照动物都死于这种疾病。使用MACVGPc假型的水疱性口炎病毒(VSV)颗粒,我们确定了Chicava和CarvalloGPc菌株之间在122位的单个氨基酸差异,该差异显着影响了兔抗血清的中和活性。这些发现表明靶向MACV糖蛋白的多克隆抗体可以在攻击后环境中防止致命感染。这些数据将有助于指导未来针对NW沙粒病毒的基于抗体的疗法开发。
    Convalescent plasma has been shown to be effective at protecting humans against severe diseases caused by New World (NW) arenaviruses, including Junin virus (JUNV) and Machupo virus (MACV). This plasma contains antibodies against the full complement of structural proteins including the nucleocapsid and envelope glycoproteins (GPcs) consisting of GP1 and GP2. To gain insights into the protective and cross-protective properties of anti-GPc-specific polyclonal antibodies, we evaluated the ability of a DNA vaccine-produced anti-GPc rabbit antisera targeting MACV strain Carvallo to provide heterologous protection against another MACV strain termed Chicava in the Hartley guinea pig model. The neutralizing activity of the rabbit antisera against the heterologous MACV strains Chicava and Mallale was found to be 54-fold and 23-fold lower, respectively, compared to the titer against the homologous MACV strain Carvallo in the PRNT50 assay. Despite lower neutralizing activity against the strain Chicava, the rabbit antisera protected 100% of the guinea pigs from this strain when administered up to four days post-infection, whereas all the control animals succumbed to the disease. Using vesicular stomatitis virus (VSV) particles pseudotyped with MACV GPc, we identified a single amino acid difference at position 122 between the strains Chicava and Carvallo GPc that significantly influenced the neutralization activity of the rabbit antisera. These findings indicate that polyclonal antibodies targeting the MACV glycoproteins can protect against lethal infection in a post-challenge setting. These data will help guide future antibody-based therapeutics development against NW arenaviruses.
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