Global vaccines and immunology最新文献

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Comparison of systemic and mucosal immunization with replicating Single cycle Adenoviruses. 复制单循环腺病毒免疫系统与粘膜免疫的比较。

Global vaccines and immunology

Pub Date : 2018-09-01 Epub Date: 2018-05-15 DOI: 10.15761/GVI.1000128

William E Matchett, Stephanie S Anguiano-Zarate, Michael A Barry

HIV-1 infections occur during sexual contact at mucosal surfaces. Vaccines need to provide mucosal barrier protection and stimulate systemic immune responses to control HIV spread. Most vaccines are delivered by systemic immunization via intramuscular (IM) injection route. While this can drive systemic and mucosal immune responses, there are data show that mucosal immunization may be superior at driving responses at mucosal barriers. To explore this question, we immunized mice with replicating single-cycle adenovirus (SC Ad) vaccines expressing clade B HIV-1 envelope (Env) by intramuscular (IM), intranasal (IN), or intravaginal (IVAG) routes to compare vaccine responses. SC-Ads generated significant antibodies against Env after only a single immunization by the IN route, but not the other routes. These animals were boosted by the same route or by the mucosal IVAG routes. IM and IN primed animals generated strong antibody responses regardless of the boosting route. In contrast, IVAG primed animals failed to generate robust antibodies whether they were boosted by the IVAG or IM routes. These data suggest there may be benefits in first educating the immune system at mucosal sites during HIV vaccination. IN and IM prime-boost were then compared in Syrian hamsters which support SC-Ad DNA replication. In this case, IN immunization again was the only route that generated significant Env antibodies after a single immunization. Following a boost by IN or IM routes, IN primed animals had significantly higher antibody responses than the IM primed animals. Env antibodies could still be detected one year after immunization, but only in animals that received at least one mucosal IN immunization. These data suggest that there is merit in vaccination by mucosal routes.

HIV-1感染发生在粘膜表面的性接触中。疫苗需要提供粘膜屏障保护和刺激全身免疫反应来控制艾滋病毒的传播。大多数疫苗是通过肌肉注射途径进行全身免疫接种。虽然这可以驱动全身和粘膜免疫反应，但有数据表明，粘膜免疫可能在驱动粘膜屏障反应方面更胜一筹。为了探讨这个问题，我们通过肌肉注射(IM)、鼻内注射(IN)或阴道内注射(IVAG)途径，用表达进化支B HIV-1包膜(Env)的复制单循环腺病毒(SC Ad)疫苗免疫小鼠，比较疫苗反应。SC-Ads仅通过IN途径单次免疫产生显著的Env抗体，而其他途径均无。这些动物通过相同的途径或粘膜IVAG途径增强。无论增强途径如何，IM和IN引发的动物都产生了强烈的抗体反应。相比之下，IVAG引物的动物无论通过IVAG或IM途径增强，都无法产生强大的抗体。这些数据表明，在接种艾滋病毒疫苗期间，首先在粘膜部位教育免疫系统可能是有益的。然后在支持SC-Ad DNA复制的叙利亚仓鼠中比较IN和IM的初始增强。在这种情况下，在单次免疫后，免疫球蛋白再次成为产生显著Env抗体的唯一途径。在通过IN或IM途径增强后，IN引发的动物的抗体反应明显高于IM引发的动物。免疫一年后仍可检测到Env抗体，但仅限于至少接种过一次粘膜in免疫的动物。这些数据表明，通过粘膜途径接种疫苗是有价值的。

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引用次数: 7

B cell responses in older adults with latent tuberculosis: Considerations for vaccine development. 老年潜伏结核患者的B细胞应答:疫苗开发的考虑

Global vaccines and immunology

Pub Date : 2016-06-01 Epub Date: 2016-05-27 DOI: 10.15761/GVI.1000112

Sina Helbig, Sergey Rekhtman, Kristen Dostie, Alexander Casler, Thomas Schneider, Natasha S Hochberg, Lisa Ganley-Leal

Reactivation of latent tuberculosis (LTBI) is more common among the aging population and may contribute to increased transmission in long-term health care facilities. Difficulties in detecting LTBI due to potential blunting of the tuberculin skin test (TST), and the lowered ability of the elderly to tolerate the course of antibiotics, underscore the need for an effective vaccine. Immuno-senescence reduces the capacity of vaccines to induce sufficient levels of protective immunity against many pathogens, further increasing the susceptibility of the elderly to infectious diseases. We sought to evaluate the response of B cells to Mycobacterium tuberculosis (Mtb) in residents of long-term care facilities to determine the feasibility of using a vaccine to control infection and transmission from reactivated LTBI. Our results demonstrate that although B cell responses were higher in subjects with LTBI, Mtb antigens could stimulate B cell activation and differentiation in vitro in TST negative subjects. B cells from elderly subjects expressed high basal levels of Toll-like receptor (TLR)2 and TLR4 and responded strongly to Mtb ligands with some activation pathways dependent on TLR2. B cells derived from blood, tonsil and spleen from younger subjects responded similarly and to the same magnitude. These results suggest that B cell responses are robust in the elderly and modifications to a TB vaccine, such as TLR2 ligand-based adjuvants, may help increase immune responses to a protective level.

潜伏性结核病(LTBI)的再激活在老龄化人口中更为常见，并可能导致长期卫生保健设施中的传播增加。由于结核菌素皮肤试验(TST)的潜在钝化，以及老年人对抗生素疗程的耐受能力下降，检测LTBI的困难突出了对有效疫苗的需求。免疫衰老降低了疫苗诱导对许多病原体产生足够水平的保护性免疫的能力，进一步增加了老年人对传染病的易感性。我们试图评估长期护理机构居民B细胞对结核分枝杆菌(Mtb)的反应，以确定使用疫苗控制重新激活的LTBI感染和传播的可行性。我们的研究结果表明，尽管LTBI受试者的B细胞反应更高，但Mtb抗原可以刺激TST阴性受试者的B细胞激活和分化。老年受试者的B细胞表达高基础水平的toll样受体(TLR)2和TLR4，并对Mtb配体有强烈反应，一些激活途径依赖于TLR2。从年轻受试者的血液、扁桃体和脾脏中提取的B细胞也有类似的反应，且强度相同。这些结果表明，B细胞反应在老年人中是强大的，对结核病疫苗的修改，如基于TLR2配体的佐剂，可能有助于将免疫反应提高到保护水平。

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引用次数: 1

Integrative representations and analyses of vaccine-induced intended protective immunity and unintended adverse events using ontology-based and theory-guided approaches. 使用基于本体和理论指导的方法对疫苗诱导的预期保护性免疫和意外不良事件进行综合表征和分析。

Global vaccines and immunology

Pub Date : 2016-05-23 DOI: 10.15761/GVI.1000110

Y. He, Edison Ong, Jiangan Xie

While effective preventive vaccines induce intended protective immunity, they also induce unintended adverse events (AEs). Generally speaking, compared to killed, inactivated vaccines and protein vaccines, live attenuated vaccines induce more protective immune responses. However, live attenuated vaccines are also associated with more AEs and even more serious AEs. For example, while live attenuated smallpox vaccines were critical to the eradication of smallpox, approximately 20–30% of smallpox vaccine recipients also experienced with various AEs that range in prevalence and severity [1]. Inter-individual variations in cytokine and AE response after smallpox vaccinations are in part due to genetic variation. For another example, the attenuated oral poliovirus vaccine (OPV) efficiently induces intestinal immunity and durable humoral immunity. However, OPV has the disadvantage of genetic instability, contributing to rare and sporadic cases of vaccine-associated paralytic poliomyelitis and the emergence of genetically divergent vaccine-derived polioviruses [2]. These AEs are worsened in patients with primary immunodeficiencies. These results suggest that the intended protective immune responses and unintended adverse events are correlated and deserve being studied simultaneously.

虽然有效的预防性疫苗可诱导预期的保护性免疫，但它们也会诱导意外的不良事件(ae)。一般来说，与灭活疫苗、灭活疫苗和蛋白疫苗相比，减毒活疫苗可引起更强的保护性免疫反应。然而，减毒活疫苗也与更多的不良反应甚至更严重的不良反应有关。例如，虽然减毒天花活疫苗对根除天花至关重要，但大约20-30%的天花疫苗接种者也经历了流行程度和严重程度不等的各种ae。天花疫苗接种后细胞因子和AE反应的个体间差异部分是由于遗传变异。例如，口服脊髓灰质炎病毒减毒疫苗(OPV)可有效诱导肠道免疫和持久体液免疫。然而，口服脊髓灰质炎具有遗传不稳定的缺点，导致疫苗相关的麻痹性脊髓灰质炎的罕见和散发病例，以及出现遗传分化的疫苗衍生脊髓灰质炎病毒[2]。这些不良事件在原发性免疫缺陷患者中更为严重。这些结果表明预期的保护性免疫反应和意外的不良事件是相关的，值得同时研究。

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引用次数: 3

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