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Chronic infectious diseases refer to diseases that require a long period of time from onset to cure or death, the use of therapeutic vaccines has recently emerged to eradicate diseases. Currently, clinical research is underway to develop therapeutic vaccines for chronic infectious diseases based on various vaccine formulations, and the recent success of the messenger RNA vaccine platform and efforts to apply it to therapeutic vaccines are having a positive impact on conquering chronic infectious diseases. However, since research on the development of therapeutic vaccines is still relatively lacking compared to prophylactic vaccines, there is a need to focus more on the development of therapeutic vaccines to overcome threats to human health caused by chronic infectious diseases. In order to accelerate the development of therapeutic vaccines for chronic infectious diseases in the future, it is necessary to establish a clear concept of therapeutic vaccines suitable for the characteristics of each chronic infectious disease, as well as standardize vaccine effectiveness evaluation methods, secure standards/reference materials, and simplify the vaccine approval procedure. [ABSTRACT FROM AUTHOR]

In the wake of the SARS-CoV-2 pandemic, inactivating bioaerosols became a pivotal issue which helps to prevent the transmittance of SARS-CoV-2. Thus, the current study was conducted to investigate a potential inactivating method using both ozone (O3) and ultraviolet C (UVC). Individual and integrated effects of O3 and UVC were compared. A solution containing approximately 4~7.3x106 CFU/mL of Salmonella typhimurium bacteria was used to produce bacteria droplets. These droplets were exposed to O3 and UVC to determine the reduction rate of bacteria. The exposure times were set as 1 and 30 minutes. Ozone concentrations were 100 and 200 ppmv. UVC-LEDs were used as a UVC source. Peak wavelength of the UVC-LED was 275 nm and the irradiation dose was 0.77 mW/cm². In terms of O3 and UVC-LED interaction, 194 ppmv styrene was used as a target compound to be removed. Considering the O3 and UVC-LED interaction, the presence of O3 could reduce the performance of the UVC-LED, and UVC-LED could also reduce significant amount of O3. The sequence of O3 and UVC-LED treatment was as follows: O3 was exposed at first, then UVC-LED, and this order showed the best reduction ratio (>99.9%). Therefore, if O3 and UVC-LED is used to disinfect Salmonella typhimurium bacteria contained in droplets, bacteria should be separately exposed to O3 and UVC-LED in order to improve the inactivation efficiency. [ABSTRACT FROM AUTHOR]

Vaccination is one of the most successful strategies to prevent diseases caused by pathogens. Although various expression systems including Escherichia coli, yeast, insect, and mammalian cells are currently used for producing many of vaccines, these conventional platforms have the limitation of post-translational modification, high cost, and expensive scalability. In this respect, the plant-based expression system has been considered as an attractive platform to produce recombinant vaccines due to fast, cost-effective and scalable production as well as safety. This review discusses the development of plant-derived vaccines and the current stage of plant-based expression system. [ABSTRACT FROM AUTHOR]

In order to develop a successful vaccine against deadly diseases with a wide range of antigenic diversity, an in-depth knowledge of the molecules and signaling mechanisms between the vaccine candidates and immune cells is required. Therefore, monitoring vaccine components, such as antigen or adjuvants, and immune cell dynamics at the vaccination site or draining lymph nodes can provide important information to understand more about the vaccine response. This review briefly introduces and describes various non-invasive molecular imaging methods for visualizing immune cell dynamics after vaccination. [ABSTRACT FROM AUTHOR]

Organoid is an in vitro multicellular form mimicking in vivo organ. Its similarity to human organ including cellular organization, molecular expression patterns, as well as genetic signatures enables to study the characteristics of infectious agents and host-pathogen interaction. For the features of organoid, this system also can be potentially used to cultivate currently uncultivable viruses of vaccine candidates. This paper will briefly describe problems in the current culture system for virus production and the possibility of organoid as culture system for viral vaccine and their current limitations that should be solved to meet the goal. [ABSTRACT FROM AUTHOR]

Purpose: Study on the pathogen and the pathogen-related disease require the information at both cellular and organism level. However, lack of appropriate high-quality antibodies and the difference between the experimental animal models make it difficult to analyze in vivo mechanism of pathogen-related diseases. For more reliable research on the infection and immuneresponse of pathogen-related diseases, accurate analysis is essential to provide spatiotemporal information of pathogens and immune activity to avoid false-positive or mis-interpretations. In this regards, we have developed a method for tracking Francisella tularensis in the animal model without using the specific antibodies for the F. tularensis. Materials and Methods: A dual reporter plasmid using GFP-Lux with putative bacterioferritin promoter (pBfr) was constructed and transformed to F. tularensis live vaccine strain to generate F. tularensis LVS (FtLVS)-GFP-Lux for both fluorescence and bioluminescence imaging. For vaccination to F. tularensis infection, FtLVS and lipopolysaccharide (LPS) from FtLVS were used. Results: We visualized the bacterial replication of F. tularensis in the cells using fluorescence and bioluminescence imaging, and traced the spatio-temporal process of F. tularensis pathogenesis in mice. Vaccination with LPS purified from FtLVS greatly reduced the bacterial replication of FtLVS in animal model, and the effect of vaccination was also successfully monitored with in vivo imaging Conclusion: We successfully established dual reporter labeled F. tularensis for cellular and whole body imaging. Our simple and integrated imaging analysis system would provide useful information for in vivo analysis of F. tularensis infection as well as in vitro experiments, which have not been fully explained yet with various technical problems. [ABSTRACT FROM AUTHOR]

Assessing antigen concentration of vaccine is essential step in determining the quality of the vaccine prior to vaccination. After vaccination, vaccine-induced antibody titer should also be measured to verify the vaccine efficacy. Since conventional assay used for vaccine concen- trations and induced Ab-titers is antibody-based enzyme-linked immunosorbent assay, the assay inevitably brings drawbacks of antibody such as high cost for production, limited stability, and inconsistent quality between lot-to-lots. Aptamer is single-stranded nucleic acid having three-dimensional structure and has features overcoming limitations of antibody. This review will briefly introduce the features of aptamer and potential of aptamer-based system for evalu- ation of vaccine efficacy. [ABSTRACT FROM AUTHOR]

Vaccination is the most efficient method for infectious disease prevention. Parenteral injections such as intramuscular, intradermal, and subcutaneous injections have several advantages in vaccine delivery, but there are many drawbacks. Thus, the development of a new vaccine delivery system has long been required. Recently, microneedles have been attracting attention as new vaccination tools. Microneedle is a highly effective transdermal vaccine delivery method due to its mechanism of action, painlessness, and ease of use. Here, we summarized the characteristics of microneedles and the possibilities as a new vaccine delivery route. [ABSTRACT FROM AUTHOR]

Since the first case of Ebola virus disease (EVD) in Guinea was reported in March 2014 by World Health Organization (WHO), the outbreak has continued through the year and the total number of 19,065 patients was reported as the confirmed or suspected in the EVD-affected countries. Among the cases, 7,388 patients were reported death by 19 December. Currently, available therapeutics to treat the infected patients or vaccines to prevent people from infection is not developed yet while viral diagnostic methods were already developed and firmly established in a lot of countries as a first step for the preparedness of Ebola outbreak. Some potential therapeutic materials including ZMapp were supplied and the treated people got over the EVD. Several candidates of vaccines also were investigated their efficacy in animal models by National Institute of Health (NIH) and Department of Defense, and they are processing of clinical tests in West Africa aiming to finish the development by the 2015. Vaccine and therapeutic development is essential to stop the EVD outbreak in West Africa, also to protect the world from the risk which can be generated by potential spread of Ebola virus. [ABSTRACT FROM AUTHOR]

Tularemia is a high-risk infectious disease caused by Gram-negative bacterium Francisella tularensis. Due to its high fatality at very low colony-forming units (less than 10), F. tularensis is considered as a powerful potential bioterrorism agent. Vaccine could be the most efficient way to prevent the citizen from infection of F. tularensis when the bioterrorism happens, but officially approved vaccine with both efficacy and safety is not developed yet. Research for the development of tularemia vaccine has been focusing on the live attenuated vaccine strain (LVS) for long history, still there are no LVS confirmed for the safety which should be an essential factor for general vaccination program. Furthermore the LVS did not show protection efficacy against high-risk subspecies tularensis (type A) as high as the level against subspecies holarctica (type B) in human. Though the subunit or recombinant vaccine candidates have been considered for better safety, any results did not show better prevention efficacy than the LVS candidate against F. tularensis infection. Currently there are some more trials to develop vaccine using mutant strains or nonpathogenic F. novicida strain, but it did not reveal effective candidates overwhelming the LVS either. Difference in the protection efficacy of LVS against type A strain in human and the low level protection of many subunit or recombinant vaccine candidates lead the scientists to consider the live vaccine development using type A strain could be ultimate answer for the tularemia vaccine development. [ABSTRACT FROM AUTHOR]

Purpose: In vaccine efficacy evaluation, visualization of pathogens in whole organism at each time point would be able to reduce the consuming animals and provide the in vivo information within consistent background with identical organism. Materials and Methods: Using IVIS spectrum whole live-animal imaging system, fluorescent intensity was optimized and visualized proportionately by concentrating Escherichia coli MC1061 strain which expresses GFP (E. coli-GFP) in BALB/C mice after injection. Results: Local distribution of disseminated E. coli-GFP was traced in each organ by fluorescence. Detached organ showed more obvious fluorescent signal, and intestine showed strongest fluorescent signal. Conclusion: This in vivo imaging method using GFP-tagged pathogen strain suggest quantified infected pathogens by fluorescence intensity in whole animals can provide the information about the localization and distribution after infection. [ABSTRACT FROM AUTHOR]

Background: The ectodomain of matrix protein 2 (M2e) of influenza A virus is a rationale target antigen candidate for the development of a universal vaccine against influenza as M2e undergoes little sequence variation amongst human influenza A strains. Vaccine-induced M2e-specific antibodies (Abs) have been shown to display significant cross-protective activity in animal models. M2e-based vaccine constructs have been shown to be more protective when administered by the intranasal (i.n.) route than after parenteral injection. However, i.n. administration of vaccines poses rare but serious safety issues associated with retrograde passage of inhaled antigens and adjuvants through the olfactory epithelium. In this study, we examined whether the sublingual (s.l.) route could serve as a safe and effective alternative mucosal delivery route for administering a prototype M2e-based vaccine. The mechanism whereby s.l. immunization with M2e vaccine candidate induces broad protection against infection with different influenza virus subtypes was explored. Methods and Results: A recombinant M2 protein with three tandem copies of the M2e (3M2eC) was expressed in Escherichia coli. Parenteral immunizations of mice with 3M2eC induced high levels of M2e-specific serum Abs but failed to provide complete protection against lethal challenge with influenza virus. In contrast, s.l. immunization with 3M2eC was superior for inducing protection in mice. In the latter animals, protection was associated with specific Ab responses in the lungs. Conclusions: The results demonstrate that s.l. immunization with 3M2eC vaccine induced airway mucosal immune responses along with broad cross-protective immunity to influenza. These findings may contribute to the understanding of the M2-based vaccine approach to control epidemic and pandemic influenza infections. [ABSTRACT FROM AUTHOR]

Background: HIV-1 specific cytotoxic T lymphocytes (CTLs) have an important role as antiviral effector cells for controlling HIV-1 infection. Methods: To investigate CTL response during the early stage of HIV infection, we measured immunity-related factors including CD4+ T cell counts, CD8+ T cell counts, HIV-1 RNA viral loads and IFN-g secretion according to CTL response in 78 selected primary HIV-1-infected Koreans. Results: The CTL response was strongly induced by HIV-1 specific Gag and Nef peptides (p = 0.016) compared with induction by Tat or Env peptides. These results suggest that the major antiviral factors inducing strong HIV-specific CTL responses are associated with the Gag and Nef viral regions in primary HIV-1 infected Koreans. The relationship between viral load and CTL response showed varying correlations with time following HIV infection. CTL response was inversely correlated with viral loads at preseroconversion stage I (r = -0.224 to -0.33) and changed to a positive correlation at the preseroconversion stage II (r = 0.132 to 0.854). Finally, it changed to an inverse correlation again after seroconversion until a viral set point was established on serological profiling (r = -0.195 to -0.407). Conclusions: These findings demonstrate a dynamic correlation between viral load and subsequent CTL responses during early HIV infection. [ABSTRACT FROM AUTHOR]

Background: In Korea, approximately 70% of HIV-positive individuals are currently diagnosed in hospitals, while most HIV-positive patients were diagnosed at public health centers in 1980 s and 1990 s. However, there are no reporting systems to identify how many HIV tests are performed in the Korean hospitals different from public health centers and Blood centers. We estimated how many HIV tests were performed in hospitals and analyzed the nationwide hospital-based HIV seroprevalence in the present study. Methods: Between 2002 and 2008, data included HIV tests on insurance claims in hospitals and the proportion of computerized insurance claims from the Health Insurance Review and Assessment Services. The number of HIV tests from the survey in the External Quality Assurance Scheme for hospital laboratories was collected to calculate the insurance claim proportion. HIV seroprevalence was estimated using data of tested individuals, including infected individuals. Statistical analysis was confirmed with the 95% confidence interval. Statistical significance was defined at p-values < 0.05. Results: The number of HIV tests in hospitals increased from 2.7 million in 2002 to 5.0 million in 2008. The trend of HIV seroprevalence was decrease (1.5-1.3 per 10,000 individuals, P < 0.0028), except in 2002. The number of women tested was greater than men, and the proportion increased in older individuals and in small towns. Men had a higher annual HIV seroprevalence than women (P < 0.0001). The annual seroprevalence decreased in men (P = 0.0037), but was stable in women. The seroprevalence in the 30-39 year age group demonstrated higher than other age groups except 2008. Conclusions: The nationwide hospital-based number of HIV tests and seroprevalence were estimated using a new method and seroprevalence trends were identified. This information will facilitate improvement in national HIV prevention strategies. [ABSTRACT FROM AUTHOR]

Background: The number of Koreans diagnosed with human immunodeficiency virus (HIV) infections is increasing annually; however, CD4+ T-cell counts at diagnosis have decreased. The purpose of the present study was to identify clinical and epidemiologic associations with low CD4+ T-cell counts at the time of HIV diagnosis in a Korean population.Methods: Data from 2,299 HIV-infected individuals with initial CD4+ T-cell counts measured within 6 months of HIV diagnosis and reason for HIV testing were recorded and measured from 2000 to 2007. Data were selected from the database of the Korea Centers for Disease Control and Prevention. Late diagnosis was defined by CD4+ T-cell counts <200 cells/mm3. Reasons for HIV testing were analyzed using logistic regression including epidemiologic variables.Results: A total of 858 individuals (37.3%) were included in the late diagnosis group. Individuals with a late diagnosis were older, exposed through heterosexual contact, and demonstrated clinical manifestations of acquired immunodeficiency syndrome (AIDS). The primary reason for HIV testing was a routine health check-up (41%) followed by clinical manifestations (31%) of AIDS. The proportion of individuals with a late diagnosis was higher in individuals tested due to clinical symptoms in public health centers (adjusted odds ratio [AOR], 17.3; 95% CI, 1.7-175) and hospitals (AOR, 4.9; 95% CI, 3.4-7.2) compared to general health check-up. Late diagnosis annually increased in individuals diagnosed by voluntary testing both in public health centers (PHCs, P = 0.017) and in hospitals (P = 0.063). Routine testing due to risky behaviors resulted in earlier detection than testing secondary to health check-ups, although this difference was not statistically significant (AOR, 0.7; P = 0.187). Individuals identified as part of hospital health check-ups more frequently had a late diagnosis (P = 0.001)Conclusions: HIV infection was primarily detected by voluntary testing with identification in PHCs and by testing due to clinical symptoms in hospitals. However, early detection was not influenced by either voluntary testing or general health check-up. It is important to encourage voluntary testing for early detection to decrease the prevalence of HIV infection and AIDS progression. [ABSTRACT FROM AUTHOR]

The author announces the selection of "Clinical Experimental Vaccine Research (CEVR)" for coverage in Emerging Sources Citation Index (ESCI) of Web of Science, Thomson Reuters in November 2015.