Ongoing Clinical Trials of Vaccines to Fight against COVID-19 Pandemic

Chakraborty Chiranjib,SHARMA ASHISH RANJAN,Bhattacharya Manojit,Sharma Garima,Saha Rudra P.,이상수 대한면역학회 2021 Immune Network Vol.21 No.1

Coronavirus disease 2019 (COVID-19) has developed as a pandemic, and it created an outrageous effect on the current healthcare and economic system throughout the globe. To date, there is no appropriate therapeutics or vaccines against the disease. The entire human race is eagerly waiting for the development of new therapeutics or vaccines against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Efforts are being taken to develop vaccines at a rapid rate for fighting against the ongoing pandemic situation. Amongst the various vaccines under consideration, some are either in the preclinical stage or in the clinical stages of development (phase-I, -II, and -III). Even, phase-III trials are being conducted for some repurposed vaccines like Bacillus Calmette–Guérin, polio vaccine, and measles-mumps-rubella. We have highlighted the ongoing clinical trial landscape of the COVID-19 as well as repurposed vaccines. An insight into the current status of the available antigenic epitopes for SARS-CoV-2 and different types of vaccine platforms of COVID-19 vaccines has been discussed. These vaccines are highlighted throughout the world by different news agencies. Moreover, ongoing clinical trials for repurposed vaccines for COVID-19 and critical factors associated with the development of COVID-19 vaccines have also been described.

Comparative Effects of Bivalent, Quadrivalent, and Nonavalent Human Papillomavirus Vaccines in The Prevention of Genotype-Specific Infection: A Systematic Review and Network Meta-Analysis

Kim Jimin,Choe Young June,Park Jungeun,Cho Jahyun,Cheong Chelim,Oh Jin-Kyoung,Park Mihai,Shim Eunha,Yu Su-Yeon 대한감염학회 2024 Infection and Chemotherapy Vol.56 No.1

Background Human papillomavirus (HPV) infection is a major global disease burden and the main cause of cervical cancer. Certain HPV genotypes, with are the most common etiologic pathogens and cause a significant disease burden, are being targeted for vaccine development. However, few studies have focused on the comparative effectiveness of the bivalent HPV (2v-HPV), quadrivalent HPV (4v-HPV), and nonavalent HPV (9v-HPV) vaccines against HPV strain-specific infection. This study investigated the comparative effects of these vaccines against genotype-specific infection. Materials and Methods We conducted a pairwise and network meta-analysis of published randomized clinical trials of HPV vaccines according to sex and HPV infection status for nine HPV genotypes (HPV 6/11/16/18/31/33/45/52/58). Results Overall, 10 randomized controlled trials (12 articles) were included in this study. In the network meta-analysis, no statistically significant differences were observed in the prevention of carcinogenic HPV strains (16/18/31/33/45/52/58) between the 2v-HPV and 4v-HPV vaccines in female HPV infection–naïve populations. However, the 9v-HPV vaccine showed a significantly superior effect compared with 2v-HPV and 4v-HPV vaccines in preventing HPV 31/33/45/52/58 infections. Although 2v-HPV and 4v-HPV vaccines provided some cross-protection against HPV 31/33/45/52/58 infections, the effect was significant only on HPV 31 infection. For HPV 16 and 18, neither statistically significant nor small differences were found in the prevention of HPV infection among the 2v-HPV, 4v-HPV, and 9v-HPV vaccines. Conclusion Our study complements previous understanding of how the effect of HPV vaccines differs according to the HPV genotype. This is important because HPV genotype prevalence varies among countries. We advocate for continued efforts in vaccinating against HPV, while public health agencies should consider the difference in the vaccine effect and HPV genotype prevalence when implementing HPV vaccination in public vaccination programs. Background Human papillomavirus (HPV) infection is a major global disease burden and the main cause of cervical cancer. Certain HPV genotypes, with are the most common etiologic pathogens and cause a significant disease burden, are being targeted for vaccine development. However, few studies have focused on the comparative effectiveness of the bivalent HPV (2v-HPV), quadrivalent HPV (4v-HPV), and nonavalent HPV (9v-HPV) vaccines against HPV strain-specific infection. This study investigated the comparative effects of these vaccines against genotype-specific infection. Materials and Methods We conducted a pairwise and network meta-analysis of published randomized clinical trials of HPV vaccines according to sex and HPV infection status for nine HPV genotypes (HPV 6/11/16/18/31/33/45/52/58). Results Overall, 10 randomized controlled trials (12 articles) were included in this study. In the network meta-analysis, no statistically significant differences were observed in the prevention of carcinogenic HPV strains (16/18/31/33/45/52/58) between the 2v-HPV and 4v-HPV vaccines in female HPV infection–naïve populations. However, the 9v-HPV vaccine showed a significantly superior effect compared with 2v-HPV and 4v-HPV vaccines in preventing HPV 31/33/45/52/58 infections. Although 2v-HPV and 4v-HPV vaccines provided some cross-protection against HPV 31/33/45/52/58 infections, the effect was significant only on HPV 31 infection. For HPV 16 and 18, neither statistically significant nor small differences were found in the prevention of HPV infection among the 2v-HPV, 4v-HPV, and 9v-HPV vaccines. Conclusion Our study complements previous understanding of how the effect of HPV vaccines differs according to the HPV genotype. This is important because HPV genotype prevalence varies among countries. We advocate for continued efforts in vaccinating against HPV, while public health agencies should consider the difference in the vaccine effect and HPV genotype prevalence when implementing HPV vaccination in public vaccination programs.

Evaluation of precipitation time of the aluminum salts adsorbed potentially frozen vaccines used in the Polish National Immunization Schedule for their pre-qualification before the administration

Paulina Górska,Małgorzata Główka,Katarzyna Woźnica,Aleksandra A. Zasada 대한백신학회 2022 Clinical and Experimental Vaccine Research Vol.11 No.2

Purpose: Vaccines adsorbed on aluminum adjuvants irreversibly lose potency after freezing and their safety is affected. To prevent the administration of such vaccines, the World Health Organization developed the Shake Test designed to determine whether adsorbed vaccines have been frozen or not. However, the Shake Test is difficult and time-consuming when routinely conducted at the place of vaccination. In this study, a modified shake test for prequalification of potentially frozen vaccines was elaborated. Materials and Methods: Vaccines used in the Polish Immunization Schedule were investigated and the analysis includes an assessment of precipitation time and the influence of the container type, amount and type of aluminum compound, and a volume of vaccine dose on the precipitation time. Results: Significant differences between the precipitation time of frozen and non-frozen vaccines routinely used in the Polish Immunization Schedule were observed. The precipitation time of all non-frozen vaccines was above 30 minutes. The longest precipitation time of frozen vaccines was 10 minutes. Conclusion: The finding of the study can be used in practice by the personnel administering vaccines to patients. Step-by-step recommendations for the preparation of the test have been proposed in the article.

현대에서의 생백신과 이에 대한 면역반응의 재평가

김경효 대한소아감염학회 2009 Pediatric Infection and Vaccine Vol.16 No.1

The vaccines has been developed over the first two hundred years since Jenner's smallpox vaccination. In modern days, vaccination has had the largest impact on the incidence and persistence of infections. Although natural infection induces lifelong immunity, the assumption that the vaccine also confers permanent protection has been reconsidered following outbreaks of measles in students who had been vaccinated 15-20 years prior to infection in the US in the 1980s. Clinical studies have proposed several mechanisms such as vaccine failure in some individuals and the subsequent loss of immunity after vaccination. An ideal vaccine is relatively easy to define, but few real vaccines approach the ideal. Many difficulties account for the failure in producing these ideal vaccines. However, recent advances in methods for studying immune response to pathogens have provided a better understanding of immune mechanisms. Based on these findings, the development of good vaccine formulations allowing stimulation of optimal and prolonged protective immunity and immunization policies or schedules should lead to the introduction of vaccines for previously resistant organisms. The vaccines has been developed over the first two hundred years since Jenner's smallpox vaccination. In modern days, vaccination has had the largest impact on the incidence and persistence of infections. Although natural infection induces lifelong immunity, the assumption that the vaccine also confers permanent protection has been reconsidered following outbreaks of measles in students who had been vaccinated 15-20 years prior to infection in the US in the 1980s. Clinical studies have proposed several mechanisms such as vaccine failure in some individuals and the subsequent loss of immunity after vaccination. An ideal vaccine is relatively easy to define, but few real vaccines approach the ideal. Many difficulties account for the failure in producing these ideal vaccines. However, recent advances in methods for studying immune response to pathogens have provided a better understanding of immune mechanisms. Based on these findings, the development of good vaccine formulations allowing stimulation of optimal and prolonged protective immunity and immunization policies or schedules should lead to the introduction of vaccines for previously resistant organisms.

The present and future of rabies vaccine in animals

Yang, Dong-Kun,Kim, Ha-Hyun,Lee, Kyung-Woo,Song, Jae-Young The Korean Vaccine Society 2013 Clinical and Experimental Vaccine Research Vol.2 No.1

<P>An effective strategy for preventing rabies consists of controlling rabies in the host reservoir with vaccination. Rabies vaccine has proven to be the most effective weapon for coping with this fatal viral zoonotic disease of warm-blooded animals, including human. Natural rabies infection of an individual is always associated with exposure to rabid animals, and the duration of clinical signs can vary from days to months. The incubation period for the disease depends on the site of the bite, severity of injury, and the amount of infecting virus at the time of exposure. The mortality of untreated cases in humans is 100%. Over the last 100 years, various rabies vaccines have been developed and used to prevent or control rabies in animals, such as modified live vaccine, inactivated rabies vaccine, and oral modified live vaccine. These have proved safe and efficacious worldwide. New-generation rabies vaccines, including recombinant rabies virus-based vaccines, vectored vaccines, DNA-based vaccines, and plant vaccines, have been explored to overcome the limitations of conventional rabies vaccines. This article discusses current and next-generation rabies vaccines in animals.</P>

5-11세 소아에서 코로나19 백신의 효능 및 안전성에 대한 체계적 문헌고찰

최미영,유수연,정채림,최영준,최수한,Choi, Miyoung,Yu, Su-Yeon,Cheong, Chelim,Choe, Young June,Choi, Soo-Han 대한소아감염학회 2022 Pediatric Infection and Vaccine Vol.29 No.1

Purpose: To evaluate the efficacy and safety of coronavirus disease 2019 (COVID-19) vaccines in children aged 5-11 years, a rapid systematic review was conducted on published clinical trials of COVID-19 vaccines and studies that analyzed real-world data on adverse events after COVID-19 vaccination. Methods: A systematic search was conducted on medical literature in international (Ovid-MEDLINE) and pre-published literature databases (medRxiv), followed by handsearching up to January 4, 2022. We used terms including COVID-19, severe acute respiratory syndrome coronavirus 2, and vaccines, and the certainty of evidence was graded using the GRADE approach. Results: A total of 1,675 studies were identified, of which five were finally selected. Among the five studies, four consisted of data from clinical trials of each of the four types of COVID-19 vaccines (BNT162b2, mRNA-1273, CoronaVac, and BBIBP-CorV). The remaining study consisted of real-world data on the safety of the BNT162b2 vaccine in children aged 5-11 years. This systematic review identified that COVID-19 vaccines in recipients aged 5-11 years produced a favorable immune response, and were vaccines were effective against COVID-19. The safety findings for the BNT162b2 vaccine in children and early adolescents aged 5-11 years were similar to those data noted in the clinical trial. Conclusions: There is limited data on COVID-19 vaccines in children aged 5-11 years. Consequently continuous and comprehensive monitoring is necessary for the evaluation of the safety and effectiveness of the COVID-19 vaccines.

Safety assessments of recombinant DTaP vaccines developed in South Korea

Choi Gi-Sub,Kang Kyu-Ri,Kim Seung-Bum,Ji Joon-Hwan,Cho Gyu-Won,Kang Hyun-Mi,Kang Jin-Han 대한백신학회 2024 Clinical and Experimental Vaccine Research Vol.13 No.2

Purpose: Pertussis bacteria have many pathogenic and virulent antigens and severe adverse reactions have occurred when using inactivated whole-cell pertussis vaccines. Therefore, inactivated acellular pertussis (aP) vaccines and genetically detoxified recombinant pertussis (rP) vaccines are being developed. The aim of this study was to assess the safety profile of a novel rP vaccine under development in comparison to commercial diphtheria-tetanusacellular pertussis (DTaP) vaccines. Materials and Methods: The two positive control DTaP vaccines (two- and tri-components aP vaccines) and two experimental recombinant DTaP (rDTaP) vaccine (two- and tri-components aP vaccines adsorbed to either aluminum hydroxide or purified oat beta-glucan) were used. Temperature histamine sensitization test (HIST), indirect Chinese hamster ovary (CHO) cell cluster assay, mouse-weight-gain (MWG) test, leukocytosis promoting (LP) test, and intramuscular inflammatory cytokine assay of the injection site performed for safety assessments. Results: HIST results showed absence of residual pertussis toxin (PTx) in both control and experimental DTaP vaccine groups, whereas in groups immunized with tri-components vaccines, the experimental tri-components rDTaP absorbed to alum showed an ultra-small amount of 0.0066 IU/mL. CHO cell clustering was observed from 4 IU/mL in all groups. LP tests showed that neutrophils and lymphocytes were in the normal range in all groups immunized with the two components vaccine. However, in the tri-components control DTaP vaccine group, as well as two- and tri-components rDTaP with beta-glucan group, a higher monocyte count was observed 3 days after vaccination, although less than 2 times the normal range. In the MWG test, both groups showed changes less than 20% in body temperature and body weight before the after the final immunizations. Inflammatory cytokines within the muscle at the injection site on day 3 after intramuscular injection revealed no significant response in all groups. Conclusion: There were no findings associated with residual PTx, and no significant differences in both local and systemic adverse reactions in the novel rDTaP vaccine compared to existing available DTaP vaccines. The results suggest that the novel rDTaP vaccine is safe.

백신의 효율적 공급을 위한 시장/정부 기능의 최적화 방안

오정일,신영수 경북대학교 법학연구원 2023 법학논고 Vol.- No.83

현대 자본주의하에서 생산과 유통이 전적으로 시장에 맡겨지고 정부가 개입하지 않는 상품이 없지만, 백신과 같이 전염병과 관련된 의약품에 대한 규제는 매우 강하다. 정부가 백신 시장에 개입하면 외부성을 제거함으로써 백신을 효율적으로 공급할 수 있으나 가격 통제, 출고량 통제, 백신 배분, 의무 접종 등으로 인해 시장의 경쟁성이 저하되고 소비자주권이 침해된다. 인가받은 백신을 독점적으로 제조 및 판매하는 사업자들의 반경쟁적 관행을 염두에 둔 제도 보완이 필요하다. 가격남용 규제의 경우 백신 개발 비용 산정이 쉽지 않은 점, 모든 백신은 개발 시점에서 최초 제품이므로 비교 대상을 찾기 어려운 점 등으로 인해 규제 수단으로 활용하기 쉽지 않다. 남용행위로서 최근 문제가 된 출고조절에 대한 현행 규정은 백신과 같은 독특한 공급 및 유통구조를 반영하지 못한 까닭에 해석상 쟁점들이 제기될 가능성이 상존한다. 백신과 같은 특정 산업을 염두에 두고 공정거래법을 개정하기는 쉽지 않다. 현실적으로 공정거래위원회 고시를 통해 기준을 명확히 하는 방안을 모색해야 할 것이다. 백신 시장에서 주로 적발되는 입찰 담합에 대응하려면 백신 조달이 보건 관련 규범에 따른 절차에 따라 진행된다는 점을 활용할 필요가 있다. 보건당국이 포착하기가 쉬운 구조이므로 경쟁 당국과의 협업을 강화하여야 한다. 반면, 경쟁법 집행이 신속한 백신 개발에 장애가 될 여지를 최소화하는 것이 바람직하다. 제약회사 간 협약 및 공동연구 개발에 대해 경쟁법 적용을 면제 또는 완화하는 국제적 경향을 고려하여, 공정거래법상 공동행위 예외인가 제도를 활용하는 것이 가능하다. 공정거래법상 요건을 추가하거나 약사법 등 보건 관련 규범에서 보건당국의 승인을 받은 경우를 공정거래법 제40조 제2항에 따른 공동행위 예외 인가를 받은 것으로 간주하도록 할 수 있다. Under modern capitalism, production and distribution are not entirely entrusted to the market, but regulations on drugs related to infectious diseases, such as vaccines, are very strong. If the government intervenes in the vaccine market, it can supply vaccines efficiently by removing externality, but price control, shipment control, vaccine ration, and mandatory vaccination reduce market competitiveness and infringe on consumer sovereignty. It is necessary to supplement the system with the anti-competitive practices of operators who exclusively manufacture and sell authorized vaccines in mind. In the case of price abuse regulation, it is not easy to use it as a regulatory means due to the difficulty of calculating vaccine development costs and the difficulty of finding a comparison target because all vaccines are the first products at the time of development. The current regulations on shipment control, which have recently become a problem as an abuse, do not reflect unique supply and distribution structures such as vaccines, so there is a possibility that issues will be raised in interpretation. It is not easy to revise the Fair Trade Act with certain industries in mind, such as vaccines. In reality, it will be necessary to seek ways to clarify the standards through the Fair Trade Commission notice. In order to cope with bid rigging, which is mainly detected in the vaccine market, it is necessary to take advantage of the fact that vaccine procurement is carried out according to procedures according to health-related norms. Since the structure is easy for health authorities to detect, cooperation with competition authorities should be strengthened. On the other hand, it is desirable to minimize the possibility that competition law enforcement will hinder rapid vaccine development. It is possible to utilize the joint action exception authorization system under the Fair Trade Act in consideration of the international trend of exempting or easing the application of competition laws for agreements between pharmaceutical companies and joint research and development. Additional requirements under the Fair Trade Act or approval from health authorities in health-related norms such as the Pharmaceutical Affairs Act may be regarded as having been approved for exceptions to joint actions under Article 40 (2) of the Fair Trade Act.

Vaccination in Pregnancy

( Min-a Kim ),( Young-han Kim ) 대한주산의학회 2022 Perinatology Vol.33 No.2

Pregnant women and newborns are vulnerable to several pathogens and are at high risk of exposure to various infectious diseases. Part of this increased susceptibility in pregnant women is due to pregnancy-related hormones that interact with the immune response. Maternal vaccination is an effective strategy for protecting the mothers as well as their infants and newborns against vaccine-preventable infections acquired at birth via transplacental transfer of maternal antibodies. At present, vaccines routinely recommended for pregnant women are the influenza and Tdap vaccines. A single dose of influenza vaccine is recommended for all pregnant women during the influenza season, which should be repeated during each pregnancy and the Tdap vaccine is recommended during every pregnancy, between 27 and 36 weeks of gestation. In addition, since pertussis infection in newborns or infants is often caused by family members and caregivers who come in direct contact with the baby, obstetrician-gynecologists should encourage the administration of the Tdap vaccine to these individuals at least 2 weeks before coming into contact with the newborn. In addition to influenza and Tdap vaccines, some vaccines such as hepatitis A and B vaccines can be used to protect from infectious diseases through vaccination in high-risk conditions or practices, such as travel to endemic areas, exposure, and during outbreaks. Maternal immunization is an important public health strategy to protect pregnant women and their babies. Healthcare providers should confidently promote vaccination during pregnancy as they are regularly trained to advise women on the latest immunization information.

Serological responses and protection levels in chickens administered with Newcastle disease vaccines

Geumji Seung,Jiye Kim,Hyobi Kim,Ji-Yeon Kim,Yang-Ho Jang,Yeon-Hee Kim,Moon Her,Seong-Joon Yi,Keun-Woo Lee,Il Jang,Young Ju Lee 대한수의학회 2022 大韓獸醫學會誌 Vol.62 No.4

Vaccination against Newcastle disease (ND) is the most effective means of controlling the disease, and these vaccines are commercialized only after their safety and effectiveness have been verified through tests that comply with Korean Standards of National Lot Release for Veterinary Biologics. This study investigated whether a relatively convenient and safe serological test can be used in place of the challenge test using highly virulent ND virus. Hemagglutination inhibition (HI) assay and enzyme-linked immunosorbent assay (ELISA) were considered positive of log2 2 or more and cutoff value of 200 or more, respectively, in both live and inactivated vaccines. However, when the antibody levels of the live and inactivated vaccines induced using the Ulster 2C, KBNP-C4152R2L, and K148/08 strains were compared, the antibody titers for inactivated vaccines were significantly higher than those for live vaccines in both the HI assay and ELISA. A strong positive correlation was observed between HI and ELISA antibody titers. The live vaccines corresponded to a survival rates of ≥ 80% and the inactivated vaccines corresponded to 100% survival rates. This study confirmed that standard efficacy tests can serve as serological tests, and can replace the challenge test and that the vaccine approval process can be improved.