• Molecules and Cells
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• 제46권1호
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• pp.41-47
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• 2023

The rapid development of mRNA vaccines has contributed to the management of the current coronavirus disease 2019 (COVID-19) pandemic, suggesting that this technology may be used to manage future outbreaks of infectious diseases. Because the antigens targeted by mRNA vaccines can be easily altered by simply changing the sequence present in the coding region of mRNA structures, it is more appropriate to develop vaccines, especially during rapidly developing outbreaks of infectious diseases. In addition to allowing rapid development, mRNA vaccines have great potential in inducing successful antigen-specific immunity by expressing target antigens in cells and simultaneously triggering immune responses. Indeed, the two COVID-19 mRNA vaccines approved by the U.S. Food and Drug Administration have shown significant efficacy in preventing infections. The ability of mRNAs to produce target proteins that are defective in specific diseases has enabled the development of options to treat intractable diseases. Clinical applications of mRNA vaccines/therapeutics require strategies to safely deliver the RNA molecules into targeted cells. The present review summarizes current knowledge about mRNA vaccines/ therapeutics, their clinical applications, and their delivery strategies.

• 한국융합학회논문지
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• 제12권8호
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• pp.179-186
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• 2021

국내 승인된 코로나-19 백신 중, mRNA 플랫폼 기반 백신의 제조공정을 중심으로 살펴보았다. 제조공정은 크게 DNA 주형 제조공정, mRNA 전사공정, 나노에멀젼화 공정, 제형화, 그리고 완제공정으로 이루어져 있다. 이 공정들은 여러 제약사 및 위탁생산회사와 협업으로 진행되고 있다. 이 중 핵심공정인 나노에멀젼화 공정은 mRNA 보호역할을 위해 지질 성분들이 필요하며, 혼합공정에는 microfluidic device를 활용하는 것으로 알려져 있다. 나노에멀젼화 공정 기술은 향후 다양한 의약품 개발에 자극제 역할을 할 것으로 기대된다.

• 대한의생명과학회지
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• 제29권4호
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• pp.231-241
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• 2023

Messenger RNA (mRNA)-based vaccines and treatments have recently emerged as a promising strategy. Naked mRNA presents various limitations for direct delivery. Therefore, in this paper, Lipid Nanoparticles (LNPs) were utilized for the delivery of mRNA. Lipid nanoparticle (LNP) mRNA systems are highly effective as vaccines, but their efficacy for pulmonary delivery has not yet been fully established. Additionally, research on effective delivery systems and administration methods for vaccines is required to resolve the stability and degradation issues associated with naked mRNA delivery. This study aimed to determine mRNA delivery efficiency via the inhalation of a lipid nanoparticle (LNP) formulation designed specifically for pulmonary delivery. To this purpose, we built a library of seven LNP configurations with different lipid molar and N/P ratios and evaluated their encapsulation efficiency using gel retardation assay. Among the tested LNPs, LNP1, LNP2-2, and LNP3-2 demonstrated high transfection efficiency in vitro based on FACS analyses luciferase assays, and intracellular accumulation tests. The mRNA delivery efficiencies of the selected LNPs after inhalation and intravenous injection were compared and evaluated. LNP2-2 showed the highest mRNA expression in healthy mouse lungs when aerosolized and was found to be non-toxic. These results indicate that LNP2-2 is a promising carrier for lung mRNA delivery via inhalation.

• Journal of Yeungnam Medical Science
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• 제39권2호
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• pp.89-97
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• 2022

More than 2 years after the explosion of the coronavirus disease 2019 (COVID-19) pandemic, extensive efforts have been made to develop safe and efficacious vaccines against infections with severe acute respiratory syndrome coronavirus 2. The pandemic has opened a new era of vaccine development based on next-generation platforms, including messenger RNA (mRNA)-based technologies, and paved the way for the future of mRNA-based therapeutics to provide protection against a wide range of infectious diseases. Multiple vaccines have been developed at an unprecedented pace to protect against COVID-19 worldwide. However, important knowledge gaps remain to be addressed, especially in terms of how vaccines induce immunogenicity and efficacy in those who are elderly. Here, we discuss the various vaccine platforms that have been utilized to combat COVID-19 and emphasize how these platforms can be a powerful tool to react quickly to future pandemics.

• Clinical and Experimental Vaccine Research
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• 제12권1호
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• pp.60-69
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• 2023

Purpose: Although the fast development of safe and effective messenger RNA (mRNA) vaccines against severe acute respiratory syndrome coronavirus 2 has been a success, waning humoral immunity has led to the recommendation of booster immunization. However, knowledge of the humoral immune response to different booster strategies and the association with adverse reactions is limited. Materials and Methods: We investigated adverse reactions and anti-spike protein immunoglobulin G (IgG) concentrations among health care workers who received primary immunization with mRNA-1273 and booster immunization with mRNA-1273 or BNT162b2. Results: Adverse reactions were reported by 85.1% after the first dose, 94.7% after the second dose, 87.5% after a third dose of BNT162b2, and 86.0% after a third dose of mRNA-1273. They lasted for a median of 1.8, 2.0, 2.5, and 1.8 days, respectively; 6.4%, 43.6%, and 21.0% of the participants were unable to work after the first, second, and third vaccination, respectively, which should be considered when scheduling vaccinations among essential workers. Booster immunization induced a 13.75-fold (interquartile range, 9.30-24.47) increase of anti-spike protein IgG concentrations with significantly higher concentrations after homologous compared to heterologous vaccination. We found an association between fever, chills, and arthralgia after the second vaccination and anti-spike protein IgG concentrations indicating a linkage between adverse reactions, inflammation, and humoral immune response. Conclusion: Further investigations should focus on the possible advantages of homologous and heterologous booster vaccinations and their capability of stimulating memory B-cells. Additionally, understanding inflammatory processes induced by mRNA vaccines might help to improve reactogenicity while maintaining immunogenicity and efficacy.

• IMMUNE NETWORK
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• 제22권3호
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• pp.24.1-24.12
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• 2022

Coronavirus disease 2019 (COVID-19) vaccination in immunocompromised, especially transplant recipients, may induce a weaker immune response. But there are limited data on the immune response after COVID-19 vaccination in liver transplant (LT) recipients, especially on the comparison of Ab responses after different vaccine platforms between mRNA and adenoviral vector vaccines. Thus, we conducted a prospective study on LT recipients who received two doses of the ChAdOx1 nCoV-19 (ChAdOx1), mRNA-1273, or BNT162b2 vaccines compared with healthy healthcare workers (HCWs). SARS-CoV-2 S1-specific IgG Ab titers were measured using ELISA. Overall, 89 LT recipients (ChAdOx1, n=16 [18%]) or mRNA vaccines (mRNA-1273 vaccine, n=23 [26%]; BNT162b2 vaccine, n=50 [56%]) received 3 different vaccines. Of them, 16 (18%) had a positive Ab response after one dose of COVID-19 vaccine and 62 (73%) after 2 doses. However, the median Ab titer after two doses of mRNA vaccines was significantly higher (44.6 IU/ml) than after two doses of ChAdOx1 (19.2 IU/ml, p=0.04). The longer time interval from transplantation was significantly associated with high Ab titers after two doses of vaccine (p=0.003). However, mycophenolic acid use was not associated with Ab titers (p=0.53). In conclusion, about 3-quarters of LT recipients had a positive Ab response after 2 doses of vaccine, and the mRNA vaccines induced higher Ab responses than the ChAdOx1 vaccine.

• 생명과학회지
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• 제33권9호
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• pp.746-753
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• 2023

바이러스성 전염병은 전 세계 공중 보건에 가장 큰 위협 중 하나로 간주된다. 최근 중증급성호흡기증후군 코로나바이러스-2(SARS-CoV-2)로 인한 COVID-19 대유행은 신종 바이러스 감염의 위협을 극명하게 상기시켜 주었다. 효율적인 백신과 치료제 개발 및 생산은 팬데믹을 퇴치할 수 있는 유일한 대안일 것이며 COVID-19 대유행은 새로운 바이러스성 질병을 통제하고 예방하기 위한 새로운 백신 플랫폼의 필요성을 보여주었다. 기존의 백신 플랫폼인 약독화 생백신, 불활성화 백신은 백신 개발 속도, 제조 등이 광범위한 백신 적용을 위한 긴급 사용에 한계가 있다. 흥미롭게도, COVID-19 예방을 위한 SARS-CoV-2 mRNA-지질나노입자(LNP) 플랫폼은 기존 백신 플랫폼 한계에 대한 효과적인 대안임이 확인되었다. 또한 COVID-19 mRNA 핵산 백신과 나노입자 기반 플랫폼은 SARS-CoV-2 및 변종 SARS-CoV-2 모두에 효과적인 백신임이 확인되었다. 이 논문에서는 mRNA 백신, 디지털 백신 및 나노입자백신 등의 차세대 백신 플랫폼을 중점으로 백신 기술 및 플랫폼의 장단점에 대해 기술하였다.

• Childhood Kidney Diseases
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• 제26권2호
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• pp.97-100
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• 2022

In response to the global coronavirus disease 2019 (COVID-19) pandemic, vaccines were developed and approved quickly. However, numerous cardiovascular adverse events have been reported. We present two adolescent cases who developed a hypertensive crisis following NT162b2 mRNA COVID-19 vaccination. Patient 1 was an 18-year-old male and his systolic blood pressure was 230 mmHg one day after the second vaccine. He was obese. No secondary cause of hypertension other than the vaccine was identified. Patient 2 was an 18-year-old male who complained with palpitation after the first vaccine. His blood pressure was 178/109 mmHg. He had autosomal dominant polycystic kidney disease. Both were treated with continuous infusion of labetalol followed by losartan, and blood pressure was controlled. Patient 2 received second vaccination and his blood pressure did not rise. It is warranted to measure blood pressure in adolescents at high risk of hypertension after NT162b2 mRNA COVID-19 vaccination.

• 대한의생명과학회지
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• 제28권2호
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• pp.67-82
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• 2022

The prevalence of SARS-CoV-2 led to inconsistent public health policies that resulted in COVID-19 containment failure. These factors resulted in increased hospitalization and death. To prevent viral spread and achieve herd immunity, the only safe and effective measure is to provide to vaccinates. Ever since the release of the SARS-CoV-2 nucleotide sequence in January of 2020, research centers and pharmaceutical companies from many countries have developed different types of vaccines including mRNA, recombinant protein, and viral vector vaccines. Prior to initiating vaccinations, phase 3 clinical trials are necessary. However, no vaccine has yet to complete a phase 3 clinical trial. Many products obtained "emergency use authorization" from governmental agencies such as WHO, FDA etc. The Korean government authorized the use of five different vaccines. The viral vector vaccine of Oxford/AstraZeneca and the Janssen showed effectiveness of 76% and 66.9%, respectively. The mRNA vaccine of Pfizer-BioNTech and Moderna showed effectiveness of 95% and 94.1%, respectively. The protein recombinant vaccine of Novavax showed an effectiveness of 90.4%. In this review, we compared the characteristics, production platform, synthesis principles, authorization, protective effects, immune responses, clinical trials and adverse effects of five different vaccines currently used in Korea. Through this review, we conceptualize the importance of selecting the optimal vaccine to prevent the COVID-19 pandemic.

• Clinical and Experimental Vaccine Research
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• 제13권1호
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• pp.10-20
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• 2024

Animal models are essential in medical research for testing drugs and vaccines. These models differ from humans in various respects, so their results are not directly translatable in humans. To address this issue, humanized mice engrafted with functional human cells or tissue can be helpful. We propose using humanized mice that support the engraftment of human hematopoietic stem cells (HSCs) without irradiation to evaluate vaccines that influence patient immunity. For infectious diseases, several types of antigens and adjuvants have been developed and evaluated for vaccination. Peptide vaccines are generally used for their capability to fight cancer and infectious diseases. Evaluation of adjuvants is necessary as they induce inflammation, which is effective for an enhanced immune response but causes adverse effects in some individuals. A trial can be done on humanized mice to check the immunogenicity of a particular adjuvant and peptide combination. Messenger RNA has also emerged as a potential vaccine against viruses. These vaccines need to be tested with human immune cells because they work by producing a particular peptide of the pathogen. Humanized mice with human HSCs that can produce both myeloid and lymphoid cells show a similar immune response that these vaccines will produce in a patient.