• Biomolecules & Therapeutics
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• v.31 no.4
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• pp.370-387
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• 2023

The COVID-19 pandemic has increased demand for safe and effective vaccines. Research to develop vaccines against diseases including Middle East respiratory syndrome, Ebolavirus, human immunodeficiency virus, and various cancers would also contribute to global well-being. For successful vaccine development, the advancement of technologies such as antigen (Ag) screening, Ag delivery systems and adjuvants, and manufacturing processes is essential. Ag delivery systems are required not only to deliver a sufficient amount of Ag for vaccination, but also to enhance immune response. In addition, Ag types and their delivery systems determine the manufacturing processes of the vaccine product. Here, we analyze the characteristics of various Ag delivery systems: plasmids, viral vectors, bacterial vectors, nanoparticles, self-assembled particles, natural and artificial cells, and extracellular vesicles. This review provides insight into the current vaccine landscape and highlights promising avenues of research for the development and improvement of Ag delivery systems.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.6
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• pp.2447-2451
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• 2014

Human papillomavirus (HPV) is the primary etiologic agent of cervical cancer. Consideration of safety and non human leukocyte antigen restriction, protein vaccine has become the most likely form of HPV therapeutic vaccine, although none have so far been reported as effective. Since tumor cells consistently express the two proteins E6 and E7, most therapeutic vaccines target one or both of them. In this study, we fabricated DC vaccines by transducing replication-defective recombinant adenoviruses expressing E6/E7 fusion gene of HPV-16, to investigate the lethal effects of specific cytotoxic T lymphocytes (CTL) against CaSki cells in vitro. Mouse immature dendritic cells (DC) were generated from bone marrow, and transfected with pAd-E6/E7 to prepare a DC vaccine and to induce specific CTL. The surface expression of CD40, CD68, MHC II and CD11c was assessed by flow cytometry (FCM), and the lethal effects of CTL against CaSki cells were determined by DAPI, FCM and CCK-8 methods. Immature mouse DC was successfully transfected by pAd-E6/E7 in vitro, and the transfecting efficiency was 40%-50%. A DC vaccine was successfully prepared and was used to induce specific CTL. Experimental results showed that the percentage of apoptosis and killing rate of CaSki cells were significantly increased by coculturing with the specific CTL (p <0.05). These results illustrated that a DC vaccine modified by HPV-16 E6/E7 gene can induce apoptosis of CaSki cells by inducing CTL, which may be used as a new strategy for biological treatment of cervical cancer.

• The Journal of Korean Academic Society of Nursing Education
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• v.23 no.4
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• pp.367-377
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• 2017

Purpose: This descriptive research study aims to investigate influential factors on human papillomavirus vaccines, among parents who have elementary school daughters. Methods: This study was conducted with 210 parents whose children are elementary school girls, aged 9 to 12 years, in G Metropolitan City. Data were collected from August 17 to September 12, 2015 using structured questionnaires. A descriptive statistical analysis, a t-test, a ${\chi}^2-test$, a Fisher's exact test, and a logistic regression using SPSS/WIN 21.0. Results: The influential factors on the human papillomavirus vaccination intention were confirmed to be three variables: cervical cancer knowledge, perceived sensitivity, and perceived barriers. Conclusion: An intervention program, both to increase the sensitivity of vaccination and to decrease barriers, should be developed so as to improve parents' health beliefs towards human papillomavirus vaccination.

• Journal of Pharmaceutical Investigation
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• v.31 no.3
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• pp.185-190
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• 2001

Human papillomavirus (HPV) infection is known to cause cervical cancers. Human papillomavirus-like particles (VLP) have been studied as preventive vaccines of cervical cancers. To develop VLP as a therapeutic gene carrier, we studied the method to encapsulate cytokine genes in virus-like particles. HPV type 16 capsid L1 genes were amplified by polymerase chain reaction and cloned into T vector. L1 gene was then inserted into baculovirus transfer vector. The clone of baculovirus encoding L1 gene was isolated and used to express L1 protein in Sf 21 insect cells. VLP were purified by CsCl density gradient and ultracentrifugation. VLP were disassembled to capsomer units by treatment of a reducing agent. Given that interleukin-2 (IL-2) genes have been used in anticancer gene therapy and as a molecular adjuvant, IL-2 cytokine plasmids were chosen as a model gene. IL-2 plasmids were incubated with the disassembled capsomer suspension. To reassemble the particles, the mixture of capsomers and cytokine plasmids was dialyzed. The disassembly and reassembly of VLP were confirmed by transmission electron microscopy. The entrapment of cytokine plasmids in reassembled VLP was tested by the stability of plasmids against DNase I. After treatment of reassembled virus-like particles with DNase I, discrete IL-2 DNA band was observed. Our results indicate that IL-2 cytokine plasmid (3.5 kb size) can be encapsulated in the virus-like particles, suggesting the potential of VLP as a gene delivery system. Moreover, VLP containing the adjuvant cytokine plasmids might function as more effective subunit vaccines.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7325-7329
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• 2013

Background: Human papillomavirus (HPV) is one of the most common sexually transmitted infectious agents, and the effectiveness of vaccine delivery programs will depend largely upon whether providers recommend vaccines. The objectives of this study were to examine pediatrician characteristics, knowledge, and attitudes associated with HPV and HPV immunization. Materials and Methods: Attendees of the national pediatric meeting in 2011, were asked to complete a questionnaire that, aside from demographic information, elicited level of agreement with statements regarding HPV, its related diseases, and HPV vaccination. It also documented attitudes and beliefs about HPV vaccination. Results: Of the 480 attendees, 226 (47%) filled in the questionnaire. The level of pediatrician HPV-related knowledge varied. The majority (78%) were aware that HPV infection is the most common sexually transmitted infection, while 51% were unaware that a condom is ineffective protection against HPV infection. Between 60-80% of respondents were aware of the effectiveness of HPV vaccination for women. On the other hand, only 10% were aware of reasons why men should be vaccinated against HPV. The majority (75%) of Turkish pediatricians were likely to recommend HPV vaccination to their daughter, if they had one. Seventy percent of pediatricians agreed that the HPV vaccination should be added to the National Immunization Program (NIP) in Turkey. However, the respondents documented concerns about the cost of the vaccination. Conclusions: Increasing pediatricians' knowledge and awareness of HPV and HPV vaccination may assist with the implementation of an effective NIP.

• IMMUNE NETWORK
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• v.10 no.6
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• pp.198-205
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• 2010

Background: A crucial limitation of DNA vaccines is its weak immunogenicity, especially in terms of eliciting antibody responses in non-human primates or humans; therefore, it is essential to enhance immune responses to vaccination for the development of successful DNA vaccines for humans. Methods: Here, we approached this issue by evaluating interleukin-7 (IL-7) as a genetic adjuvant in cynomolgus monkeys immunized with multigenic HCV DNA vaccine. Results: Codelivery of human IL-7 (hIL-7)-encoding DNA appeared to increase DNA vaccine-induced antibody responses specific for HCV E2 protein, which plays a critical role in protecting from HCV infection. HCV-specific T cell responses were also significantly enhanced by codelivery of hIL-7 DNA. Interestingly, the augmentation of T cell responses by codelivery of hIL-7 DNA was shown to be due to the enhancement of both the breadth and magnitude of immune responses against dominant and subdominant epitopes. Conclusion: Taken together, these findings suggest that the hIL-7-expressing plasmid serves as a promising vaccine adjuvant capable of eliciting enhanced vaccine-induced antibody and broad T cell responses.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.6
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• pp.2587-2592
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• 2012

Background: Limited human papillomavirus (HPV) related knowledge might be a barrier to future vaccine acceptance. From 2008-2010, PATH conducted an HPV vaccination demonstration project in partnership with the government immunization program in Vietnam, which included awareness campaigns prior to vaccination. Objective: To assess and compare knowledge and attitudes about cervical cancer and HPV vaccines between mothers and daughters, and whether knowledge was associated with vaccination status. Methods: We analyzed HPV-related knowledge and attitude data from mother-daughter paired responses to a cross-sectional household survey. After parents completed the survey, daughters were asked the same questions. We calculated the frequency of responses for each question and devised a scaled composite measure for knowledge. Results: Participants believed they had received enough information about cervical cancer and HPV vaccines and it was sufficient to make a decision about vaccination. Fifty percent of the participants knew HPV causes cervical cancer and 80% knew the HPV vaccine prevented cervical cancer. Mothers had more knowledge about cervical cancer and HPV infection (p<0.01), compared to daughters, who had more vaccine specific knowledge (p<0.01). However, the total mean knowledge score was similar for the groups. Girls not fully vaccinated had a lower mean knowledge score than fully vaccinated girls (p<0.001). Conclusions: Our results suggest that the purpose of the HPV vaccine was clearly messaged; however, some misconceptions about cervical cancer and HPV still exist. Limited knowledge about the magnitude of cervical cancer, HPV as a cause of cervical cancer, and HPV vaccines may have contributed to incomplete vaccination.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.8
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• pp.3983-3988
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• 2016

Background: Cervical cancer though preventable is still the leading cause of cancer death among women secondary to breast cancer. Persistent infection with HPV has been causally linked to the disease. A school based HPV vaccination program was introduced in late 2010 in Malaysia and nurse support is essential for its success. Objectives: To determine nurses knowledge and attitudes about HPV infection and its vaccines, and factors associated with their knowledge. Materials and Methods: This cross-sectional study was conducted among nurses working at primary health clinics in Kelantan from mid-June till the end of July 2014. Its involved 330 nurses selected through multistage random sampling. A validated self-administered questionnaire consisting of 11 items for the knowledge domain and eight items for the attitude domain was used. Results: The response rate of the study was 93.7%. The mean knowledge and mean attitude (SD) scores were 5.37 (1.76) and 29.8 (3.51) respectively. Only 24% knew that HPV is the most common sexually transmitted infection and 67% correctly answered that Gardasil vaccine can protect against four types of HPV. Nearly 60% of participants wrongly answered that HPV vaccines cannot be offered to sexually active women. Likewise, 70.9% participants were not aware that HPV vaccine may be appropriate for females aged 9 through 26 years. Though 90% of participants believed that the vaccine is safe, nearly half of them were unsure about efficacy. From multiple linear regression analysis, among the factors tested only participant's level of education showed a statistically significant association with the HPV knowledge score (p <0.001). Conclusions: This study indicates nurses have favorable attitudes towards HPV vaccination; however they have significant knowledge deficit and major misunderstanding in critical knowledge items. Among the factors tested, nursing qualification is the only factor that is significantly associated with the nurses knowledge score.

• Korean Journal of Veterinary Service
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• v.35 no.3
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• pp.169-174
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• 2012

Japanese encephalitis virus (JEV) is one of the main causes of viral encephalitis in human and animals. For over 30 years, a live attenuated JEV vaccine strain has been used in the veterinary field, and it is required to conduct quality evaluation studies on the commercial vaccines. For the quality control of live attenuated JEV vaccine, we investigated the nucleotide sequence similarity of prME gene derived from five JEV vaccines commercially available in pigs in Korea. The Vero cells infected with JEV vaccines showed specific cytopathic effect, which was characterized by rounding and detached cells. In the phylogenetic analysis, all of the vaccine strains showed a close relationship with the original vaccine seed strain (Anyang 300) and clustered into the genotype 3. In comparison of the nucleotide and deduced amino acid sequences of prME genes with the original strain, all JEV vaccine strains showed high amino acid similarity ranging from 98.9% to 99.5%, but had several point mutations, probably due to high mutation rates of viral RNA polymerase by several virus passages. Even though the current JEV vaccine strains have been maintained and produced for a long period of time, the genetic characterization of them have been rarely changed. However, since the mid 1990's, molecular epidemiology of JEV has been changed sharply from genotype 3 to genotype 1 in Korea, further studies on new vaccine strains to genotype 1 is required for more effective prevention in the field.

• Journal of Korean Medical Science
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• v.33 no.51
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• pp.340.1-340.14
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• 2018

Background: Various pneumococcal vaccines have been evaluated for immunogenicity by opsonophagocytic assay (OPA). A multiplexed OPA (MOPA) for 13 pneumococcal serotypes was developed by Nahm and Burton, and expanded to 26 serotypes in 2012. The development of new conjugate vaccines with increased valence has necessitated expanded MOPAs to include these additional serotypes. In this study, we validated this expanded MOPA platform and applied to measure antibodies against 11 additional serotypes (2, 8, 9N, 10A, 11A, 12F, 15B, 17F, 20B, 22F, and 33F) in human sera. Methods: All materials, including serum, complement, bacterial master stocks, and HL-60 cells, were evaluated for assay optimization. Following optimization, the assay was validated for accuracy, specificity, and intra- and inter-assay precision with sera from adult donors following standard protocols. The assay was applied to evaluate functional antibodies of 42 sera immunized with 23-valent pneumococcal polysaccharide vaccine (PPV23). Results: The expanded MOPA platform was specific for all serotypes, with the exception of serotype 20. The assay results were highly correlated with those obtained from single-serotype OPA, indicating acceptable accuracy. The coefficients of variation were 7%-24% and 13%-39% in tests of intra- and inter-assay precision, respectively, using three quality-control samples. A MOPA that included 11 additional serotypes in the PPV23 was established and validated with respect to accuracy, specificity, and precision. The opsonic indices of immune sera were obtained using this validated assay. Conclusion: The expanded MOPA will be useful for evaluation of the immunogenicity of PPV23 and future conjugate vaccine formulations.