• 한국동물위생학회지
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• 제45권2호
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• pp.71-77
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• 2022

African swine fever (ASF) is a fatal viral disease in pigs, with a short incubation period and causing immediate death. Few studies exist on the Asian epidemic ASF virus (ASFV) challenge in older pigs, including growing and fattening pigs and sows. We aimed to investigate clinical outcomes, pathomorphological lesions, and viral distribution in organs of 3-month-old growing pigs that were inoculated with the ASFV isolated in Vietnam. The clinical outcomes were recorded daily, and the dead or euthanized pigs immediately underwent necropsy. Viral loads were determined in 10 major organs using quantitative polymerase chain reaction. The average incubation period in growing pigs was more delayed (5.2±0.9 dpi) than that in weaned pigs, and the clinical signs were milder in growing pigs than in weaned pigs. The digestive and respiratory clinical signs in growing pigs showed at the end period of life, but these were observed at an early stage of infection in weaned pigs. The pathomorphological features were severe and nonspecific with hemorrhagic lesions in various organs. The viral loads in organs from growing pigs were higher than those from piglets, and the number of viral copies was related to gross lesions in the tonsil and intestine. In the absence of vaccines against ASF, early clinical detection is important for preventing the spread of the virus. Our findings elucidated that the clinical signs and gross lesions in growing pigs differed from those in weaned pigs, which provide valuable information for diagnosis of pigs with suspected ASF infection.

• Biomolecules & Therapeutics
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• 제31권3호
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• pp.350-358
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• 2023

Hand-foot-and-mouth disease (HFMD) is a viral infectious disease that occurs in children under 5 years of age. Its main causes are coxsackievirus (CV) and enterovirus (EV). Since there are no efficient therapeutics for HFMD, vaccines are effective in preventing the disease. To develop broad coverage against CV and EV, the development of a bivalent vaccine form is needed. The Mongolian gerbil is an efficient and suitable animal model of EV71 C4a and CVA16 infection used to investigate vaccine efficacy following direct immunization. In this study, Mongolian gerbils were immunized with a bivalent inactivated EV71 C4a and inactivated CVA16 vaccine to test their effectiveness against viral infection. Bivalent vaccine immunization resulted in increased Ag-specific IgG antibody production; specifically, EV71 C4a-specific IgG was increased with medium and high doses and CVA16-specific IgG was increased with all doses of immunization. When gene expression of T cell-biased cytokines was analysed, Th1, Th2, and Th17 responses were found to be highly activated in the high-dose immunization group. Moreover, bivalent vaccine immunization mitigated paralytic signs and increased the survival rate following lethal viral challenges. When the viral RNA content was determined from various organs, all three doses of bivalent vaccine immunization were found to significantly decrease viral amplification. Upon histologic examination, EV71 C4a and CVA16 induced tissue damage to the heart and muscle. However, bivalent vaccine immunization alleviated this in a dose-dependent manner. These results suggest that the bivalent inactivated EV71 C4a/CVA16 vaccine could be a safe and effective candidate HFMD vaccine.

• 생명과학회지
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• 제33권2호
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• pp.199-207
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• 2023

Post-COVID-19 시대에 다가올 전염병의 위협에 대비하기 위해 인간, 동물, 환경의 건강이 하나라는 One-health 개념에 기반한 연구가 필수적이다. 현재 인간의 SARS-CoV-2의 높은 감염률과 바이러스 부하로 인해 종을 뛰어넘는 감염이 확인되고 있다. 대표적으로 사람에서 밍크로의 전파 가능성이 확인되었고, 밀접 접촉 중에 사람에서 고양이로 전파가 가능할 것으로 추정되고 있다. 현재까지의 자료를 통해 가축류, 가금류에서의 감염 가능성이 낮은 것으로 보여지나 새로운 변이로 인해 감염이 확립된다면 인간의 식량 안보, 경제, 무역 등 다양한 분야에 파급 효과가 클 것으로 예측된다. 또한 SARS-CoV-2의 풍토화 전망과 반려동물로의 접근성이 높다는 점 등이 우려되는 상황이다. 바이러스의 진화는 동물 숙주에서 발생할 가능성이 높고, 다른 종에서 SARS-CoV-2가 확립되면 인간 집단에 바이러스가 다시 출현할 수 있는 중간 숙주 역할을 할 수도 있기 때문이다. SARS-CoV-2의 동물 감염에 대한 연구 데이터를 지속적으로 축적하여 빠른 대응이 필요하다고 생각된다. 또한 동물 감염에 대한 연구는 SARS-CoV-2 백신 및 치료제 연구에 사용되는 동물 모델의 개발 등을 포함한 다방면에서 중요하다. 따라서 본 연구에서는 SARS-CoV-2의 동물 감염에 대해 역학 검토 및 대응 전략을 One-health 관점에서 접근하여 분석하였다.

• 한국어병학회지
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• 제36권2호
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• pp.311-321
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• 2023

Miamensis avidus에 대한 alginate Microsphere (Alginate MS) 경구백신의 넙치에 대한 효능을 침지와 주사경로의 공격감염으로 확인하였다. Trial 1에서는 불활화 M. avidus (IMa)와 IMa를 alginate로 코팅한 IMa+Alginate MS 를 사료와 혼합하였으며 총 5일 동안 3.75 × 10⁶ cells/fish의 농도로 먹였다. 경구백신 투여 5주 후 침지로 공격감염했을 때, IMa+Alginate MS 그룹의 상대생존율 (RPS)은 50% (50% 해수 침지감염)와 37.5% (100% 해수 침지감염)였다. IMa 단독투여 그룹은 낮은 생존율을 보였다. Trial 2에서는 항원을 2.38 × 10⁶ cells/fish의 농도로 5일간 나누어 먹였다. 경구백신 투여 2주 후에는 복강주사로 효능을 평가하였고, IMa+Alginate MS 투여구의 상대생존율은 30.8%였으며 IMa 단독투여 그룹은 백신의 투여효과가 전혀 없었다. 경구백신 투여 종료 5주 후 50% 해수에서 침지감염으로 공격감염 한 경우 IMa+Alginate MS 투여구의 상대생존율은 42.9%, IMa 단독투여 그룹의 상대생존율은 14.3%를 기록하였다. 본 연구의 결과는 Alginate로 M. avidus항원을 코팅함으로써 M. avidus항원을 단독으로 투여하는 것보다 넙치에 높은 방어력을 제공할 수 있음을 나타낸다.

• IMMUNE NETWORK
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• 제23권5호
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• pp.39.1-39.15
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• 2023

Coronavirus disease 2019 (COVID-19) vaccination may non-specifically alter the host immune system. This study aimed to evaluate the effect of COVID-19 vaccination on hepatitis B surface Ag (HBsAg) titer and host immunity in chronic hepatitis B (CHB) patients. Consecutive 2,797 CHB patients who had serial HBsAg measurements during antiviral treatment were included in this study. Changes in the HBsAg levels after COVID-19 vaccination were analyzed. The dynamics of NK cells following COVID-19 vaccination were also examined using serial blood samples collected prospectively from 25 healthy volunteers. Vaccinated CHB patients (n=2,329) had significantly lower HBsAg levels 1-30 days post-vaccination compared to baseline (median, -21.4 IU/ml from baseline), but the levels reverted to baseline by 91-180 days (median, -3.8 IU/ml). The velocity of the HBsAg decline was transiently accelerated within 30 days after vaccination (median velocity: -0.06, -0.39, and -0.04 log₁₀ IU/ml/year in pre-vaccination period, days 1-30, and days 31-90, respectively). In contrast, unvaccinated patients (n=468) had no change in HBsAg levels. Flow cytometric analysis showed that the frequency of NK cells expressing NKG2A, an NK inhibitory receptor, significantly decreased within 7 days after the first dose of COVID-19 vaccine (median, -13.1% from baseline; p<0.001). The decrease in the frequency of NKG2A⁺ NK cells was observed in the CD56^dimCD16⁺ NK cell population regardless of type of COVID-19 vaccine. COVID-19 vaccination leads to a rapid, transient decline in HBsAg titer and a decrease in the frequency of NKG2A⁺ NK cells.

• IMMUNE NETWORK
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• 제23권6호
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• pp.43.1-43.10
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• 2023

The continuous emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants has provided insights for updating current coronavirus disease 2019 (COVID-19) vaccines. We examined the neutralizing activity of Abs induced by a BA.4/5-containing bivalent mRNA vaccine against Omicron subvariants BN.1 and XBB.1.5. We recruited 40 individuals who had received a monovalent COVID-19 booster dose after a primary series of COVID-19 vaccinations and will be vaccinated with a BA.4/5-containing bivalent vaccine. Sera were collected before vaccination, one month after, and three months after a bivalent booster. Neutralizing Ab (nAb) titers were measured against ancestral SARS-CoV-2 and Omicron subvariants BA.5, BN.1, and XBB.1.5. BA.4/5-containing bivalent vaccination significantly boosted nAb levels against both ancestral SARS-CoV-2 and Omicron subvariants. Participants with a history of SARS-CoV-2 infection had higher nAb titers against all examined strains than the infection-naïve group. NAb titers against BN.1 and XBB.1.5 were lower than those against the ancestral SARS-CoV-2 and BA.5 strains. These results suggest that COVID-19 vaccinations specifically targeting emerging Omicron subvariants, such as XBB.1.5, may be required to ensure better protection against SARS-CoV-2 infection, especially in high-risk groups.

• IMMUNE NETWORK
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• 제22권5호
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• pp.42.1-42.20
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• 2022

Vaccination with tumor peptide epitopes associated with MHC class I molecules is an attractive approach directed at inducing tumor-specific CTLs. However, challenges remain in improving the therapeutic efficacy of peptide epitope vaccines, including the low immunogenicity of peptide epitopes and insufficient stimulation of innate immune components in vivo. To overcome this, we aimed to develop and test an innovative strategy that elicits potent CTL responses against tumor epitopes. The essential feature of this strategy is vaccination using tumor epitope-loaded nanoparticles (NPs) in combination with polyinosinic-polycytidylic acid (poly-IC) and anti-PD1 mAb. Carboxylated NPs were prepared using poly(lactic-co-glycolic acid) and poly(ethylene/maleic anhydride), covalently conjugated with anti-H-2K^b mAbs, and then attached to H-2K^b molecules isolated from the tumor mass (H-2^b). Native peptides associated with the H-2K^b molecules of H-2K^b-attached NPs were exchanged with tumor peptide epitopes. Tumor peptide epitope-loaded NPs efficiently induced tumor-specific CTLs when used to immunize tumor-bearing mice as well as normal mice. This activity of the NPs significantly was increased when co-administered with poly-IC. Accordingly, the NPs exerted significant anti-tumor effects in mice implanted with EG7-OVA thymoma or B16-F10 melanoma, and the anti-tumor activity of the NPs was significantly increased when applied in combination with poly-IC. The most potent anti-tumor activity was observed when the NPs were co-administered with both poly-IC and anti-PD1 mAb. Immunization with tumor epitope-loaded NPs in combination with poly-IC and anti-PD1 mAb in tumor-bearing mice can be a powerful means to induce tumor-specific CTLs with therapeutic anti-tumor activity.

• IMMUNE NETWORK
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• 제23권4호
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• pp.33.1-33.13
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• 2023

Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been acknowledged as an effective mean of preventing infection and hospitalization. However, the emergence of highly transmissible SARS-CoV-2 variants of concern (VOCs) has led to substantial increase in infections among children and adolescents. Vaccine-induced immunity and longevity have not been well defined in this population. Therefore, we aimed to analyze humoral and cellular immune responses against ancestral and SARS-CoV-2 variants after two shots of the BNT162b2 vaccine in healthy adolescents. Although vaccination induced a robust increase of spike-specific binding Abs and neutralizing Abs against the ancestral and SARS-CoV-2 variants, the neutralizing activity against the Omicron variant was significantly low. On the contrary, vaccine-induced memory CD4⁺ T cells exhibited substantial responses against both ancestral and Omicron spike proteins. Notably, CD4⁺ T cell responses against both ancestral and Omicron strains were preserved at 3 months after two shots of the BNT162b2 vaccine without waning. Polyfunctionality of vaccine-induced memory T cells was also preserved in response to Omicron spike protein. The present findings characterize the protective immunity of vaccination for adolescents in the era of continuous emergence of variants/subvariants.

• Clinical and Experimental Vaccine Research
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• 제12권3호
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• pp.249-259
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• 2023

Purpose: Since patients on hemodialysis (HD) are known to be vulnerable to coronavirus disease 2019 (COVID-19), many studies were conducted regarding the effectiveness of the COVID-19 vaccine in HD patients in Western countries. Here, we assessed antibody response of HD patients for 6 months post-vaccination to identify the duration and effectiveness of the COVID-19 vaccine in the Asian population. Materials and Methods: We compared antibody response of the COVID-19 vaccine in HD patients with healthy volunteers. Patient and control groups had two doses of ChAdOx1 nCoV-19 and mRNA-1273, respectively. Immunoglobulin G (IgG) was measured before vaccination, 2 weeks after the first dose, 2 and 4 weeks, 3 and 6 months after the second dose. Neutralizing antibody was measured before vaccination and at 2 weeks, 3 and 6 months after second dose. Since the third dose was started in the middle of the study, we analyzed the effect of the third dose as well. Results: Although antibody production was weaker than the control group (n=22), the patient group (n=39) showed an increase in IgG and neutralizing antibody after two doses. And, 21/39 patients and 14/22 participants had a third dose (BNT162b2 or mRNA-1273 in the patient group, mRNA-1273 in the control group), and it did not affect antibody response in both group. Trend analysis showed IgG and neutralizing antibody did not decrease over time. Age, sex, and HD vintage did not affect antibody production in HD patients. Patients with higher body mass index displayed better seroresponse, while those on immunosuppressants showed poor seroresponse. Conclusion: Two doses of vaccination led to significant antibody response in HD patients, and the antibody did not wane until 6 months.

• Clinical and Experimental Vaccine Research
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• 제12권3호
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• pp.240-248
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• 2023

Purpose: We reported a survey-based study assessing the parental intention to vaccinate children of 5 to 7 years old against coronavirus disease 2019 (COVID-19). The aim of this study is to assess factors influencing the parental intention to vaccinate their children against COVID-19. Materials and Methods: This study adopted a cross-sectional design, held at the public health center of Senen district, Jakarta, Indonesia from November 1-30, 2022. The off-line questionnaires were distributed via the school administrator to all eligible parents. Factors associated with intention to vaccinate were analyzed with the regression logistic models. Results: Of the 435 parents in this study, 215 had already vaccinated their children against COVID-19 (49.4%), and the overall intention of the participants to vaccinate was 69.7%. Factors associated with intention to vaccinate the children against COVID-19 were parental employment status, parental COVID-19 vaccine status and concern of contracting COVID-19. Parents who are employed, had completed vaccines with COVID-19 booster vaccine, and had concern of their children contracting COVID-19 were more likely to vaccinate their children (odds ratio [OR], 2.10; 95% confidence interval [CI], 1.22-3.69; p=0.011; OR, 2.15; 95% CI, 1.21-3.83; p=0.013; OR, 2.40; 95% CI, 1.34-4.30; p=0.004, respectively). Concern on the vaccine's side effects was negatively associated with the willingness to vaccinate. Conclusion: This study showed that childhood COVID-19 vaccine only covered half of the population, with parental intentions for childhood COVID-19 vaccination being high, reaching almost two-thirds of the study participants. Factors influencing parental intentions were employment status, parental COVID-19 vaccine status, concerns about COVID-19 and concerns about vaccine side effects.