Establishing a Framework for Evaluating the Effectiveness of Vaccines Targeting National Vaccination Programs.

BACKGROUND: The increasing number of vaccines and the complexity of immunization programs, along with continuous changes in the epidemiology of infectious diseases, necessitate a systematic approach to vaccine effectiveness (VE) evaluation. This study presents a preliminary survey to establish a VE evaluation framework in Korea, focusing on the National Immunization Program. METHODS: Experts' opinions were collected through a two-round online survey targeting key stakeholders. The first round consisted of two multiple-choice questions and two open-ended questions. The second round was a quantitative survey with 17 questionnaires based on five domains derived by analyzing the results of the first-round survey. RESULTS: The results emphasize the necessity and urgency of a government-led VE evaluation system and the establishment of a multidisciplinary evaluation organization. Key considerations include personnel, budget, data integration, legal standards, and surveillance system enhancements. CONCLUSION: These findings provide valuable insights for policymakers, emphasizing the need for collaboration, financial support, and robust data management in developing evidence-based vaccination policies.

Intranasal Vaccination with Outer-Membrane Protein of Orientia tsutsugamushi induces Protective Immunity Against Scrub Typhus.

Scrub typhus develops after the individual is bitten by a trombiculid mite infected with Orientia tsutsugamushi. Since it has been reported that pneumonia is frequently observed in patients with scrub typhus, we investigated whether intranasal (i.n.) vaccination with the outer membrane protein of O. tsutsugamushi (OMPOT) would induce a protective immunity against O. tsutsugamushi infection. It was particular interest that when mice were infected with O. tsutsugamushi, the bacteria disseminated into the lungs, causing pneumonia. The i.n. vaccination with OMPOT induced IgG responses in serum and bronchoalveolar lavage (BAL) fluid. The anti-O. tsutsugamushi IgA Abs in BAL fluid after the vaccination showed a high correlation of the protection against O. tsutsugamushi. The vaccination induced strong Ag-specific Th1 and Th17 responses in the both spleen and lungs. In conclusion, the current study demonstrated that i.n. vaccination with OMPOT elicited protective immunity against scrub typhus in mouse with O. tsutsugamushi infection causing subsequent pneumonia.

Sustained Vaccination Coverage during the Coronavirus Disease 2019 Epidemic in the Republic of Korea.

Amid the COVID-19 pandemic, vaccination coverage may decline due to limited accessibility to healthcare. We assessed the impact of the COVID-19 pandemic on vaccination coverage and the incidence of vaccine-preventable diseases (VPDs) in the Republic of Korea. National vaccination coverage of 10 essential vaccines administered to children between January-June 2019 and January-June 2020 was analyzed. The national incidence of selected VPDs was compared for the corresponding periods. During the COVID-19 outbreak, the vaccination rate in children aged 0-35 months in Korea did not decrease significantly, whereas the vaccination rate for children aged 4-6 years decreased by 1.4-1.9%. The overall incidence of VPDs decreased by 10-50% between 2019 and 2020, especially with varicella. Thus, the COVID-19 pandemic did not result in a decrease in vaccination coverage among Korean children, which prevented a surge in VPD incidence. Maintaining essential vaccination coverage without interruption is important during the response to the COVID-19 pandemic.

Case Report: Scrub Typhus and Q Fever Coinfection.

A 56-year-old female goat herder had scrub typhus that persisted after receiving doxycycline for 5 days. Her symptoms continued, prompting us to perform further examinations that revealed coinfection of Q fever and scrub typhus via molecular and serological testing. We also isolated Orientia tsutsugamushi using BALB/c mice and L929 cells.

Molecular Epidemiology of an Orientia tsutsugamushi Gene Encoding a 56-kDa Type-Specific Antigen in Chiggers, Small Mammals, and Patients from the Southwest Region of Korea.

A phylogenetic analysis of Orientia tsutsugamushi was performed to elucidate its antigenic diversity in chiggers, small mammals, and patients. Between September 2014 and December 2016, a total of 3,816 chiggers were identified within nine species of four genera in the southwest region of Korea: Leptotrombidium scutellare (49.9%; 1,907/3,816), Leptotrombidium orientale (21.1%; 804/3,816), Leptotrombidium pallidum (12.4%; 474/3,816), Euchoengastia koreaensis (7.2%; 273/3,816), Leptotrombidium palpale (6.7%; 256/3,816), Neotrombicular gardellai (1.3%; 50/3,816), Leptotrombidium zetum (0.8%; 32/3,816), Walchia fragilis (0.5%; 18/3,816), and Neotrombicular japonica (> 0.1%; 2/3,816). Twelve chiggers (11 L. scutellare and one L. palpale) tested positive for O. tsutsugamushi by polymerase chain reaction and, except for 1 chigger (KY266830), were part of the Boryong strain cluster. Of the 413 small mammals that were analyzed for O. tsutsugamushi, Apodemus agrarius was the most common rodent species (89.5%; 370/413), followed by Crocidura lasiura (6.8%; 28/413) and Myodes regulus (3.6%; 15/413). The sequence identity of an O. tsutsugamushi sample obtained from the A. agrarius sample population belonged to the Saitama strain cluster. Furthermore, a phylogenetic analysis in 125 patients revealed four clusters (Boryong cluster: 82.4% [103/125], Karp: 13.6% [17/125], Kawasaki: 3.2% [4/125], and Saitama: 0.8% [1/125]). This study clarified the phylogenetic relationship for O. tsutsugamushi in chiggers, small mammals, and patients. The Boryong strain was the most common strain in chiggers and patients. In addition, various strains were identified, except for the Boryong strain, in the southwest region of Korea. Overall, the data presented here will be helpful for the establishment of prevention strategies for scrub typhus.

A Recombinant 47-kDa Outer Membrane Protein Induces an Immune Response against Orientia tsutsugamushi Strain Boryong.

We investigated the 47-kDa outer membrane protein (OMP), which is a periplasmic serine protease and an antigenic major surface protein of Orientia tsutsugamushi, as a vaccine candidate. We developed a conventional subunit vaccine expressing recombinant 47-kDa OMP (rec47) and a DNA vaccine (p47). In mouse immunization experiments, intranasal immunization with rec47 alone or with rec47 plus heat-labile enterotoxin B subunit from Escherichia coli or plus cholera toxin (CT) as adjuvants induced a higher amount of rec47-specific antibodies than intramuscular immunization with p47 alone or with p47 plus pBOOST2-samIRF7/3 (pB) as adjuvant. Moreover, the combination of rec47 and CT induced a strong cellular immune response to 47-kDa OMP, as demonstrated by a spleen cell proliferation assay, and also induced Th1- and Th2-type cytokine production, as demonstrated by a cytokine enzyme-linked immunosorbent assay. Intranasal immunization with rec47 plus CT was the most effective method for the induction of humoral and cell-mediated immune responses. Furthermore, relatively strong protection against homologous O. tsutsugamushi strain Boryong challenge was observed in mice immunized with rec47 plus CT. Therefore, 47-kDa OMP is an attractive candidate for developing a prophylactic vaccine against scrub typhus by O. tsutsugamushi infection.

Protective immunity of 56-kDa type-specific antigen of Orientia tsutsugamushi causing scrub typhus.

Scrub typhus, caused by infection with Orientia tsutsugamushi, is a mite-borne zoonotic disease endemic to the Asian-Pacific region. In Korea, the incidence of this disease has increased with climate changes, and over 10,000 cases of infection were reported in 2013. Although this infection is treatable with antibiotics such as doxycycline and azithromycin, an effective prophylactic vaccine against O. tsutsugamushi would be more desirable for preventing scrub typhus in endemic areas. In this study, we investigated the 56-kDa type-specific antigen (TSA56), which is a major outer membrane protein of O. tsutsugamushi, as a vaccine candidate. Intranasal immunization of recombinant TSA56 (rec56) induced a higher level of TSA56- specific IgG than that induced by intramuscular immunization of tsa56-expressing DNA (p56). Both types of immunization induced a cell-mediated immune response to TSA56, as demonstrated by the splenic cell proliferation assay. Mice immunized with p56, followed by rec56 plus heat-labile enterotoxin B subunit from E. coli, had a stronger protection from a homologous challenge with the O. tsutsugamushi Boryong strain than with other combinations. Our preliminary results suggest that an effective human vaccine for scrub typhus can include either recombinant TSA56 protein or tsa56-expressing DNA, and provide the basis for further studies to optimize vaccine performance using additional antigens or different adjuvants.

Orientia tsutsugamushi infection induces CD4+ T cell activation via human dendritic cell activity.

Orientia tsutsugamushi, a gram-negative bacterium, causes severe acute febrile illness in humans. Despite this danger, the route of infection, infectivity, and protective mechanisms of the host's immune response to O. tsutsugamushi are unclear. Dendritic cells (DCs) are one of the most important cell types in bridging the innate and adaptive immune responses. In this study, we observed that O. tsutsugamushi infects and replicates in monocyte-derived DCs (MODCs). During infection and replication, the expressions of the cytokines IL-12 and TNF-α, as well as the co-stimulatory molecules CD80, CD83, CD86, and CD40, were increased in MODCs. When O. tsutsugamushi-treated MODCs were co-cultured with autologous CD4(+) T cells, they enhanced production of IFN-γ, a major Th1 cytokine. Collectively, our results show that O. tsutsugamushi can replicate in MODCs and can simultaneously induce MODC maturation and increase proinflammatory cytokine levels in MODCs that subsequently activate CD4(+) T cells.