Sooseong You

Reduced Antibody Responses to the Pandemic (H1N1) 2009 Vaccine after Recent Seasonal Influenza Vaccination

ABSTRACT The vaccination program against the 2009 pandemic H1N1 influenza virus (2009 H1N1) provided a unique opportunity to determine if immune responses to the 2009 H1N1 vaccine were affected by a recent, prior vaccination against seasonal influenza virus. In the present study, we studied the immune responses to the 2009 H1N1 vaccine in subjects who either received the seasonal influenza virus vaccination within the prior 3 months or did not. Following 2009 H1N1 vaccination, subjects previously given a seasonal influenza virus vaccination exhibited significantly lower antibody responses, as determined by hemagglutination inhibition assay, than subjects who had not received the seasonal influenza virus vaccination. This result is compatible with the phenomenon of “original antigenic sin,” by which previous influenza virus vaccination hampers induction of immunity against a new variant. Our finding should be taken into account for future vaccination programs against pandemic influenza virus outbreaks.

Adjuvant effect of bacterial outer membrane vesicles with penta-acylated lipopolysaccharide on antigen-specific T cell priming

Outer membrane vesicles (OMV) are nano-sized spherical blebs shed by Gram-negative bacteria and have been utilized in vaccine development. In the present study, we evaluated T cell adjuvant activity of OMV with strictly penta-acylated LPS produced by ΔmsbB/ΔpagP mutant of non-pathogenic Escherichia coli W3110 (mOMV) compared to OMV with hexa-acylated LPS produced by wild-type E. coli W3110 (wOMV). Penta-acylation of LPS renders mOMV less endotoxic than wOMV in in vitro and in vivo toxicity assays. In mice, mOMV has adjuvant activity on T cell priming not only in KLH protein immunization but also in SIINFEKL peptide immunization. The T-cell adjuvant activity of mOMV was comparable to that of wOMV and LPS and was abrogated in TLR4 K/O mice. In innate immunity, mOMV stimulated BMDCs to up-regulate co-stimulatory and antigen-presenting molecules and to produce pro-inflammatory cytokines in a TLR4-dependent manner. Of note, mOMV induced cytokine production at a significantly less extent compared with wOMV. Taken together, we propose that mOMV with penta-acylated LPS is a safe vaccine adjuvant for T cell priming and can be used in vaccine development against viral diseases and cancer.

Driving frequency effect on electron heating mode transition in capacitive discharge

A study was conducted on the dependence of the electron heating mode transition upon driving frequency in capacitive discharge. The evolution of the electron energy distribution functions (EEDFs) over a wide range of gas pressures was investigated at different driving frequencies. Regardless of the driving frequency, the measured EEDFs exhibited a typical evolution of EEDF from bi-Maxwellian distribution to Druyvesteyn-like distribution with gas pressure, signifying the electron heating mode transition from collisionless to collisional heating. However, the gas pressure, which the heating mode transition takes place, significantly decreased as the driving frequency increased. This result is ascribed to the fact that the collisionless stochastic heating becomes inefficient at high frequency compared with collisional heating.

Korean Studies on Blood Stasis: An Overview

Blood stasis is one of the important pathological concepts in Korean medicine. We analyzed the Korean studies concerning blood stasis. We searched for articles in eight electronic databases from their inception to September, 2014. We included reviews, clinical studies, and preclinical studies that had studied blood stasis and excluded articles in which blood stasis was not mentioned or in which the original authors had not explained blood stasis. Of 211 total included studies, 19 were reviews, 52 were clinical studies, and 140 were preclinical articles. “Stagnant blood within the body” was the most frequently mentioned phrase of the traditional concept of blood stasis. Traumatic injury was the most frequently studied disease/condition in the clinical studies. In the preclinical studies, coagulopathy was studied most frequently, followed by hyperviscosity, hyperlipidemia, inflammation, neoplasm, ischemic brain injury, and atherosclerosis. Hyeolbuchukeo-tang and Angelicae Gigantis Radix were the most frequent formula and single herb, respectively, used in the blood stasis researches. The results showed that blood stasis was mainly recognized as disorder of circulation and many studies showed the effectiveness of activating blood circulating herbs for diseases and pathologies such as traumatic injury or coagulopathy. Further studies are needed in the pathologic mechanisms and various diseases of blood stasis.

Antibody-Secreting Cells with a Phenotype of Ki-67low, CD138high, CD31high, and CD38high Secrete Nonspecific IgM during Primary Hepatitis A Virus Infection

Although studies investigating the nature of Ab-secreting cells (ASCs) during acute infection with influenza or dengue virus found that the ASC response was dominated by virus-specific IgG secretion, the Ag specificity and phenotype of ASCs during primary acute viral infection were not identified. To this end, we investigated the nature of ASCs in direct ex vivo assays from patients with acute hepatitis A caused by primary infection with hepatitis A virus (HAV). We found that the frequency of CD27highCD38high ASCs was markedly increased in the peripheral blood during the acute phase of HAV infection. Moreover, substantial numbers of ASCs were non-HAV–specific and dominantly secreted IgM. We detected HAV-specific ASCs by staining with fluorochrome-tagged HAV-VP1 protein. As compared with HAV-specific ASCs, non-HAV–specific ASCs were Ki-67lowCD138highCD31highCD38high, demonstrating that non-HAV–specific ASCs had a bone marrow plasma cell–like phenotype whereas HAV-specific ASCs had a phenotype typical of circulating plasmablasts. These data suggest that non-HAV–specific ASCs might be mobilized plasma cells from the bone marrow or the spleen, whereas HAV-specific ASCs were newly generated plasmablasts. In this study, we provide evidence that pre-existing plasma cells are released into the circulation and contribute to Ag-nonspecific secretion of IgM during primary HAV infection.

Melanocyte-specific CD8+ T cells are associated with epidermal depigmentation in a novel mouse model of vitiligo

In the present study, we established a novel murine model of vitiligo by sequential prime/boost immunizations into the hind footpad and tail dermis with tyrosinase‐related protein 2 (TRP2)‐180 (SVYDFFVWL) peptide, lipopolysaccharides and cytosine–phosphate–guanosine (CpG) oligodeoxynucleotides. Immunized mice developed epidermal depigmentation in the tail skin without hair depigmentation, thereby differentiating this approach from established models of vitiligo. Following intradermal tail immunization, activated CD8+ interferon (IFN)‐γ+ T cells were recruited locally to the tail skin. In‐vivo cytotoxicity assays demonstrated specific lysis of TRP2‐180‐presenting cells in immunized mice. Furthermore, the extent of skin depigmentation correlated with the frequency of TRP2‐180‐specific splenic CD8+ T cells, as determined by IFN‐γ and tumour necrosis factor (TNF)‐α production, and cytotoxic degranulation evidenced by CD107a staining. These findings suggest a correlation between the presence of TRP2‐180‐specific CD8+ effector T cells and the development of depigmented skin lesions in our vitiligo model. This new model of vitiligo, characterized by skin depigmentation without hair depigmentation, is more similar to human disease than previous murine models. Therefore, this model is well suited to future studies on the pathogenesis of vitiligo and the development of novel therapeutics for vitiligo.

The use of maca (Lepidium meyenii) to improve semen quality: A systematic review

The aim of this review was to assess the evidence for the effectiveness of maca (Lepidium meyenii) in improving semen quality. We searched 11 databases from their inception to March 2016 and included all clinical trials on the improvement of semen quality parameters in infertile and healthy men, regardless of the study design or the type of maca. The risk of bias for each study was assessed using the Cochrane criteria. The selection of studies, data extraction, and validation were performed independently by the first two authors. Discrepancies were resolved through discussion by the same two authors. Five studies - 3 randomized clinical trials (RCTs) and 2 uncontrolled observational studies (UOSs) - met all of the inclusion criteria. One RCT found favorable effects of maca on sperm mobility in infertile men. The two other RCTs showed positive effects of maca on several semen quality parameters in healthy men. The two UOSs also suggested favorable effects of maca on semen quality. The results of our systematic review provide suggestive evidence for the effectiveness of maca in improving semen quality. However, the total number of trials, the total sample size, and the risk of bias of the included studies prevent the drawing firm conclusions. More rigorous studies are warranted.

Expert opinions on the concept of blood stasis in China: An interview study

ObjectiveTo study various experts’ opinions on the defifinition and diagnosis of blood stasis in China.MethodsWe e-mailed the selected experts to explain the purpose of the study and to invite them to participate and asked them to name a time for the investigator to call them. Eight experts and fifive organizations were interviewed in the research community investigating blood stasis in China.ResultsSix main categories emerged from the interviews: (1) blood stasis concepts; (2) blood stasis-related biomarkers; (3) methods of diagnosing blood stasis; (4) drugs for promoting blood circulation and dissipating stasis; (5) blood stasis-related diseases; and (6) blood stasis-related societies. The consensus among the interviewed experts was that the defifinition of blood stasis is rather complicated and that there is no gold standard marker for detecting blood stasis.ConclusionsThis paper acquired experts’ opinions on the defifinition and diagnosis of blood stasis in order to establish a modern concept of blood stasis. This paper also developed a diagnostic tool and diagnostic indices for blood stasis and identifified biological indices and pathologic mechanisms related to blood stasis, which might be of great reference value in future blood stasis standardization research.

Innate-like Cytotoxic Function of Bystander-Activated CD8+ T Cells Is Associated with Liver Injury in Acute Hepatitis A

Summary Acute hepatitis A (AHA) involves severe CD8+ T cell‐mediated liver injury. Here we showed during AHA, CD8+ T cells specific to unrelated viruses became activated. Hepatitis A virus (HAV)‐infected cells produced IL‐15 that induced T cell receptor (TCR)‐independent activation of memory CD8+ T cells. TCR‐independent activation of non‐HAV‐specific CD8+ T cells were detected in patients, as indicated by NKG2D upregulation, a marker of TCR‐independent T cell activation by IL‐15. CD8+ T cells derived from AHA patients exerted innate‐like cytotoxicity triggered by activating receptors NKG2D and NKp30 without TCR engagement. We demonstrated that the severity of liver injury in AHA patients correlated with the activation of HAV‐unrelated virus‐specific CD8+ T cells and the innate‐like cytolytic activity of CD8+ T cells, but not the activation of HAV‐specific T cells. Thus, host injury in AHA is associated with innate‐like cytotoxicity of bystander‐activated CD8+ T cells, a result with implications for acute viral diseases. Graphical Abstract Figure. No Caption available. HighlightsDuring acute hepatitis A (AHA), non‐HAV‐specific memory CD8+ T cells are activatedNon‐HAV‐specific CD8+ T cells are activated by IL‐15 produced by HAV‐infected cellsCD8+ T cells of AHA patients exert TCR‐independent, innate‐like cytotoxicityInnate‐like cytotoxicity of CD8+ T cells is associated with liver injury in AHA &NA; During acute hepatitis A, hepatitis A virus (HAV)‐infected cells produce IL‐15 that induces TCR‐independent bystander activation of non‐HAV‐specific memory CD8+ T cells. These CD8+ T cells exert innate‐like cytotoxicity triggered by NKG2D and NKp30 without TCR engagement. The severity of liver injury is associated with activation and innate‐like cytotoxicity of non‐HAV‐specific CD8+ T cells, but not the activation of HAV‐specific T cells. Thus, IL‐15‐induced bystander‐activated CD8+ T cells are implicated in host injury during acute viral infection.

Immunogenicity of MenACWY-CRM in Korean Military Recruits: Influence of Tetanus-Diphtheria Toxoid Vaccination on the Vaccine Response to MenACWY-CRM

The quadrivalent meningococcal conjugate vaccine (MenACWY-CRM) has been introduced for military recruits in Korea since 2012. This study was performed to evaluate the immunogenicity of MenACWY-CRM in Korean military recruits. In addition, the influence of tetanus-diphtheria toxoids (Td) vaccination on the vaccine response to MenACWY-CRM was analyzed. A total of 75 military recruits were enrolled. Among them, 18 received a dose of MenACWY-CRM only (group 1), and 57 received Td three days before MenACWY-CRM immunization (group 2). The immunogenicity of MenACWY-CRM was compared between the two groups. The serum bactericidal activity with baby rabbit complement was measured before and three weeks after immunization against serogroups A, C, W-135, and Y. The geometric mean titers (GMTs) against four serogroups were significantly increased in both groups after immunization. Compared to group 2, group 1 exhibited significantly higher vaccine responses in several aspects: post-immune GMTs against serogroup A and C, seroresponse rates against serogroup A, and a fold increases of titers against serogroup A, C, and Y. MenACWY-CRM was immunogenic against all vaccine-serogroups in Korean military recruits. Vaccine response to MenACWY-CRM was influenced by Td administered three days earlier.