Assessing the pyrogenicity of whole influenza virus particle vaccine in cynomolgus macaques.

Among inactivated influenza vaccines, the whole virus particle vaccine (WPV) elicits superior priming responses to split virus vaccine (SV) in efficiently inducing humoral and cellular immunity. However, there is concern for undesired adverse events such as fever for WPV due to its potent immunogenicity. Therefore, this study investigated the febrile response induced by subcutaneous injection with quadrivalent inactivated influenza vaccines of good manufacturing grade for pharmaceutical or investigational products in cynomolgus macaques. Body temperature was increased by 1 °C-2 °C for 6-12 h after WPV administration at the first vaccination but not at the second shot, whereas SV did not affect body temperature at both points. Given the potent priming ability of WPV, WPV-induced fever may be attributed to immune responses that uniquely occur during priming. Since WPV-induced fever was blunted by pretreatment with indomethacin (a cyclooxygenase inhibitor), the febrile response by WPV is considered to depend on the increase in prostaglandins synthesized by cyclooxygenase. In addition, WPV, but not SV, induced the elevation of type I interferons and monocyte chemotactic protein 1 in the plasma; these factors may be responsible for pyrogenicity caused by WPV, as they can increase prostaglandins in the brain. Notably, sufficient antibody responses were acquired by half the amount of WPV without causing fever, suggesting that excessive immune responses to trigger the febrile response is not required for acquired immunity induction. Thus, we propose that WPV with a reduced antigen dose should be evaluated for potential clinical usage, especially in naïve populations.

Complete Genome Sequence of Bacillus cereus Strain HT18, Isolated from Forest Soil.

The genome sequence of Bacillus cereus strain HT18, isolated from forest soil, was 5,333,415 bp long. The genome included 5,825 putative coding sequences and 35.2% GC content; the strain had 5 plasmids. Average nucleotide identity based on BLAST+ (ANIb) and digital DNA-DNA hybridization (dDDH) results showed that HT18 was 98.78% and 90.70% homologous, respectively, to B. cereus ATCC 14579T.

Elevated trauma exposure and mental health burden among men who have sex with men in Vietnam.

The purpose of this study was to characterize trauma exposure and mental health burden among men who have sex with men (MSM) in Hanoi, Vietnam. Participants comprise 100 HIV-positive and 98 high-risk, HIV-negative MSM, ranging from 18 to 29 years of age. Data were collected using the Childhood Trauma Questionnaire, Traumatic Events Inventory, Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, and PTSD Symptom Scale. A subset of participants (n = 12) were also interviewed to evaluate community perception of the prevalence, causation, and available treatment options for mental health issues within the MSM community in Vietnam. In our sample, 23.2% reported having experienced moderate-to-severe childhood physical abuse; 18.7% physical neglect; 13.6% emotional abuse; 11.1% emotional neglect; and 26.8% sexual abuse. Such trauma exposure continued into adulthood and manifested most commonly in the form of interpersonal violence. Approximately 37.4% of the sample met the criteria for probable PTSD; 26.8% for moderate-to-severe depression; and 20.2% for moderate-to-severe anxiety. Neither exposure nor mental health burden differed by serostatus. Linear regression revealed that childhood emotional abuse was the only sub-type of trauma significantly associated with depression, anxiety, and PTSD symptoms. The majority of interviewees believed that mental health burden was higher among MSM relative to the general population and attributed this to their vulnerability to interpersonal violence and lack of available coping resources. However, few believed that these mental health issues warranted clinical attention, and only one participant was able to identify a mental health service provider. Our findings suggest that trauma exposure and mental health burden are prevalent among MSM, irrespective of serostatus, and much higher than what has been previously reported among the general population in Vietnam.

Potent priming by inactivated whole influenza virus particle vaccines is linked to viral RNA uptake into antigen presenting cells.

Current detergent or ether-disrupted split vaccines (SVs) for influenza do not always induce adequate immune responses, especially in young children. This contrasts with the whole virus particle vaccines (WPVs) originally used against influenza that were immunogenic in both adults and children but were replaced by SV in the 1970s due to concerns with reactogenicity. In this study, we re-evaluated the immunogenicity of WPV and SV, prepared from the same batch of purified influenza virus, in cynomolgus macaques and confirmed that WPV is superior to SV in priming potency. In addition, we compared the ability of WPV and SV to induce innate immune responses, including the maturation of dendritic cells (DCs) in vitro. WPV stimulated greater production of inflammatory cytokines and type-I interferon in immune cells from mice and macaques compared to SV. Since these innate responses are likely triggered by the activation of pattern recognition receptors (PRRs) by viral RNA, the quantity and quality of viral RNA in each vaccine were assessed. Although the quantity of viral RNA was similar in the two vaccines, the amount of viral RNA of a length that can be recognized by PRRs was over 100-fold greater in WPV than in SV. More importantly, 1000-fold more viral RNA was delivered to DCs by WPV than by SV when exposed to preparations containing the same amount of HA protein. Furthermore, WPV induced up-regulation of the DC maturation marker CD86 on murine DCs, while SV did not. The present results suggest that the activation of antigen-presenting DCs, by PRR-recognizable viral RNA contained in WPV is responsible for the effective priming potency of WPV observed in naïve mice and macaques. WPV is thus recommended as an alternative option for seasonal influenza vaccines, especially for children.

Draft Genome Sequence of Enterobacter kobei M4-VN, Isolated from Potatoes with Soft Rot Disease.

Enterobacter kobei M4-VN, isolated from potatoes with soft rot disease in Vietnam, contains a total of 4,754,309 bp with 4,424 predicted coding sequences and a G+C content of 55.1%.

Characterization and Genome Structure of Virulent Phage EspM4VN to Control Enterobacter sp. M4 Isolated From Plant Soft Rot.

Enterobacter sp. M4 and other bacterial strains were isolated from plant soft rot disease. Virulent phages such as EspM4VN isolated from soil are trending biological controls for plant disease. This phage has an icosahedral head (100 nm in diameter), a neck, and a contractile sheath (100 nm long and 18 nm wide). It belongs to the Ackermannviridae family and resembles Shigella phage Ag3 and Dickeya phages JA15 and XF4. We report herein that EspM4VN was stable from 10°C to 50°C and pH 4 to 10 but deactivated at 70°C and pH 3 and 12. This phage formed clear plaques only on Enterobacter sp. M4 among tested bacterial strains. A one-step growth curve showed that the latent phase was 20 min, rise period was 10 min, and an average of 122 phage particles were released from each absorbed cell. We found the phage's genome size was 160,766 bp and that it annotated 219 open reading frames. The genome organization of EspM4VN has high similarity with the Salmonella phage SKML-39; Dickeya phages Coodle, PP35, JA15, and Limestone; and Shigella phage Ag3. The phage EspM4VN has five tRNA species, four tail-spike proteins, and a thymidylate synthase. Phylogenetic analysis based on structural proteins and enzymes indicated that EspM4VN was identified as a member of the genus Agtrevirus, subfamily Aglimvirinae, family Ackermannviridae.

Intravenous Infusion of Human Adipose Tissue-Derived Mesenchymal Stem Cells to Treat Type 1 Diabetic Mellitus in Mice: An Evaluation of Grafted Cell Doses.

Mesenchymal stem cell (MSC) transplantation is a novel treatment for diabetes mellitus, especially type 1 diabetes. Many recent publications have demonstrated the efficacy of MSC transplantation on reducing blood glucose and increasing insulin production in both preclinical and clinical trials. However, the investigation of grafted cell doses has been lacking. Therefore, this study aimed to evaluate the different doses of MSCs on treatment of type 1 diabetes in mouse models. MSCs were isolated and expanded from human adipose tissue. Streptozotocin (STZ)-induced diabetic mice were divided into two groups that were intravenously transfused with two different doses of human MSCs: 106 or 2.106 cells/mouse. After transplantation, both grafted and placebo mice were monitored weekly for their blood glucose levels, glucose and insulin tolerance, pancreatic structural changes, and insulin production for 56 days after transplantation. The results showed that the higher dose of MSCs (2.106 cells/mouse) remarkably reduced death rate. The death rates were 50%, 66%, and 0% in placebo group, low-dose (1.106 MSCs) group, and high-dose (2.106 MSCs) group, respectively, after 56 days of treatment. Moreover, blood glucose levels were lower for the high-dose group compared to other groups. Glucose and insulin tolerance, as well as insulin production, were significantly improved in mice transplanted with 2.106 cells. The histochemical analyses also support these results. Thus, a higher (e.g., 2.106) dose of MSCs may be an effective dose for treatment of type 1 diabetes mellitus.

Prevalence of Escherichia coli in surface waters of Southeast Asian cities.

Surface water samples were collected from rivers which fed into large urban areas within Vietnam, Indonesia, Cambodia, and Thailand and were processed to enumerate Escherichia coli. Selected isolates were further characterized using PCR to detect the presence of specific virulence genes. Analyzing the four countries together, the approximate mean cfu/100 ml for E. coli counts in the dry season were log 4.3, while counts in the wet season were log 2.8. Of the 564 E. coli isolates screened for the presence of pathogenic genes, 3.9 % possessed at least one virulence gene. The most common pathogenic types found were Shiga toxin-producing E. coli isolates. These results reinforce the importance of monitoring urban surface waters for fecal contamination, that E. coli in these water environments may serve as opportunistic pathogens, and may help in determining the impact water usage from these rivers have on the public health of urban populations in Southeast Asia.