• Journal of Pharmaceutical Investigation
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• 제31권3호
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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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• 제15권6호
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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.

• Asian Pacific Journal of Cancer Prevention
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• 제14권12호
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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.

• Asian Pacific Journal of Cancer Prevention
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• 제17권8호
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• pp.3663-3673
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• 2016

Cervical cancer (CaCx) is the second most fatal cancer contributing to 14% of cancers in Indian females, which account for 25.4% and 26.5% of the global burden of CaCx prevalence and mortality, respectively. Persistent infection with high-risk human papilloma virus (HPV- strains 16 and 18) is the most important risk factor for precursors of invasive CaCx. Comprehensive prevention strategies for CaCx should include screening and HPV vaccination. Three screening modalities for CaCx are cytology, visual inspection with acetic acid, and HPV testing. There is no Indian national policy on CaCx prevention, and screening of asymptomatic females against CaCx is practically non-existent. HPV vaccines can make a major breakthrough in the control of CaCx in India which has high disease load and no organized screening program. Despite the Indian Government's effort to introduce HPV vaccination in the National Immunization Program and bring down vaccine cost, challenges to implementing vaccination in India are strong such as: inadequate epidemiological evidence for disease prioritization, duration of vaccine use, parental attitudes, and vaccine acceptance. This paper reviews the current epidemiology of CaCx and HPV in India, and the current status of HPV vaccination in the country. This article stresses the need for more research in the Indian context, to evaluate interventions for CaCx and assess their applicability, success, scalability and sustainability within the constraints of the Indian health care system.

• IMMUNE NETWORK
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• 제3권2호
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• pp.118-125
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• 2003

Background: Disialoganglioside GD2 is a tumor-associated antigen that is overexpressed on tumor cells of neuroectodermal origin, such as melanoma and neuroblastoma. Anti-idiotypic antibodies that mimic GD2 may induce more effective immune responses than GD2 antigen itself, because they are protein antigens and are known to be able to break immune tolerance. In this study, to explore the potential of anti-idiotypic antibodies as tumor vaccines, the ability of anti-idiotypic antibodies (Ab2) to induce anti-anti-idiotypic antibodies (Ab3) that bind to the original antigen GD2 was investigated. Methods: Six monoclonal anti-idiotypic antibodies (1A8, 1G5, 2B6, 3A4, 3D6, 3H9) to monoclonal antibody M2058, which is a monoclonal antibody to GD2, were produced in mice. Three (1A8, 3A4, 3H9) of them were selected based on their ability to inhibit the binding of Ab1 to D142.34 (murine melanoma cell expressing GD2). These 3 different Ab2 were injected into rabbits, and rabbit Ab3 induced by each of them were characterized. Results: Ab3-containing sera from two rabbits immunized with 1A8, 3A4, or 3H9 bound significantly (P<0.05) to D142.34 but not to B78.96 (GD2-negative cell), and bound significantly (P<0.05) to isolated GD2 but not to GD1a. Ab3-containing sera from two rabbits immunized with 3A4 or 3H9 inhibited significantly (P<0.05) the binding of Ab1 M2058 to D142.34, and inhibited significantly (P<0.05) the binding of Ab1 M2058 to the Ab2. Conclusion: These results suggest that anti-idiotypic antibodies 3A4 and 3H9 have a potential to be used as vaccines against tumors expressing GD2 by inducing GD2-specific antibodies (Ab3).

• BMB Reports
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• 제33권3호
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• pp.249-255
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• 2000

The Haemophilus influenzae type b (Hib) has been a major cause of bacterial meningitis in children who are less than two years old. The variable (V) region repertoire of adult Caucasian antibodies (Abs) to Hib polysaccharide (PS) has been characterized well. The majority of adult antibodies against Hib uses VL that is derived from the Vk gene A2 and have arginine at the N region. In order to explore the possibility those antibody responses to Hib-PS is variable in various age groups, we examined the VL regions of the antibodies to Hib-PS in Korean adults and children. We immunized Korean adults (n = 8) and children (n = 39) with Hib tetanus conjugated vaccines, isolated RNAs from the peripheral lymphocytes, and amplified the A2-derived VL regions by RT-PCR. The PCR products were subcloned and sequenced. Forty-seven out of 54 independent clones from children used the $J{\kappa}2$, or $J{\kappa}3$ gene in preference. The adults, however, used all of the $J{\kappa}$ genes evenly. With respect to the amino acid sequences of variable regions, adult $A2-J{\kappa}$ recombinants have a germline sequence. But, the 76th codon (AGC) of child $A2-J{\kappa}2$ recombinants was substituted with CGC (arginine) in most cases (88 %) and 77 percent of child clones using the $A2-J{\kappa}3$ genes have isoleucine-109 at the junction of $J{\kappa}-C{\kappa}$ instead of threonine that is found in a germline sequence. These results suggest that the mechanism of antibody production in young children is different from that of adults.

• Journal of Preventive Medicine and Public Health
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• 제51권1호
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• pp.15-22
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• 2018

Objectives: The use of administrative data is an affordable alternative to conducting a difficult large-scale medical-record review to estimate the scale of adverse events. We identified adverse events from 2002 to 2013 on the national level in Korea, using International Classification of Diseases, tenth revision (ICD-10) Y codes. Methods: We used data from the National Health Insurance Service-National Sample Cohort (NHIS-NSC). We relied on medical treatment databases to extract information on ICD-10 Y codes from each participant in the NHIS-NSC. We classified adverse events in the ICD-10 Y codes into 6 types: those related to drugs, transfusions, and fluids; those related to vaccines and immunoglobulin; those related to surgery and procedures; those related to infections; those related to devices; and others. Results: Over 12 years, a total of 20 817 adverse events were identified using ICD-10 Y codes, and the estimated total adverse event rate was 0.20%. Between 2002 and 2013, the total number of such events increased by 131.3%, from 1366 in 2002 to 3159 in 2013. The total rate increased by 103.9%, from 0.17% in 2002 to 0.35% in 2013. Events related to drugs, transfusions, and fluids were the most common (19 446, 93.4%), followed by those related to surgery and procedures (1209, 5.8%) and those related to vaccines and immunoglobulin (72, 0.3%). Conclusions: Based on a comparison with the results of other studies, the total adverse event rate in this study was significantly underestimated. Improving coding practices for ICD-10 Y codes is necessary to precisely monitor the scale of adverse events in Korea.

• Pediatric Infection and Vaccine
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• 제15권1호
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• pp.5-11
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• 2008

Primary rotavirus gastroenteritis infection usually occurs in infants under 2 years of age worldwide regardless of level of hygiene, quality of water, food or sanitation or type of behavior. In Korea, the disease mostly occurred in infants under 2 year old, and usually in late fall to early winter with the highest incidence shown in November until early 1990s. However, since then, relatively the age incidence of this infection has increased in children over 2 years old, and it has mainly occurred in late winter to early spring with the highest incidence shown between February and March. And rotavirus gastroenteritis serotypes varied year to year as well as varied by year within the same region in our country. The comparison of severity scores between age groups in Korea showed that severity score was lowest in infants less than 3 months and highest in infants more than 6 months and less than 12 months, and hospitalization period between age groups was longest in infants older than 3 months and less than 3 months and highest in infants more than 6 months and less than 12 months and less than 6 months. In this aspect, rotavirus vaccines should be given to infants less than 2 years of age in whom the incidence of rotavirus gastroenteritis is the highest, and vaccination should be ideally started before 3 months considering hospitalization period and severity of rotavirus gastroenteritis. However, It should be careful for the introduction of new rotavirus vaccine, and the effectiveness of rotavirus vaccines should be assessed by long-term post marketing surveillance. And we guess an multivalent vaccine may be an ideal rotavirus vaccine to prevent primary infection caused by variable rotavirus strains in Korea. In addition, clinical epidemiology studies on rotavirus gastroenteritis which evaluate the age and serotypes related severity should be continuously conducted in various regions.

• Asian Pacific Journal of Cancer Prevention
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• 제16권12호
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• pp.4895-4900
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• 2015

Physician recommendation is an important predictor of HPV vaccine acceptance; however, physician willingness and preferences regarding HPV vaccination may be influenced by factors including patient age, vaccine type, and cost. A cross-sectional survey was administered to a convenience sample of health care providers in Da Nang, Vietnam, to evaluate awareness, perceptions about HPV and HPV vaccines, and willingness to vaccinate a female patient. Willingness to vaccinate was evaluated using a full-factorial presentation of scenarios featuring the following factors: vaccine cost (free vs 1,000,000 VND), patient age (12, 16, or 22 years), and HPV vaccine type (bivalent vs quadrivalent). Responses from 244 providers were analyzed; providers had a mean age of $34{\pm}11.9$ years; a majority were female, married, and had children of their own. Thirty-six percent specialized in obstetrics/gynecology and 24% were providers in family medicine. Of the three factors considered in conjoint analysis, vaccine cost was the most important factor in willingness to vaccinate, followed by patient age, and vaccine type. The most favorable scenario for vaccinating a female patient was when the vaccine was free, the patient was 22 years of age, and the HPV4 vaccine was described. In multivariable analysis, older age, being a physician, being married, and having children were all associated with increased willingness to recommend HPV vaccination (p<0.05). Provider willingness is an important aspect of successful HPV vaccination programs; identifying preferences and biases in recommendation patterns will highlight potential areas for education and intervention.

• Asian Pacific Journal of Cancer Prevention
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• 제15권13호
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• pp.5469-5474
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• 2014

Background: This study aimed to examine the level of knowledge, attitude, acceptance, and willingness to pay (WTP) for HPV vaccination among female parents of girls aged 12-15 years in Thailand. Materials and Methods: A cross-sectional survey was conducted in eight schools across Bangkok. Results: Of 1,200 questionnaires sent out, a total of 861 questionnaires were received. Knowledge regarding the HPV vaccine among parents was quite low. Only half of the parents knew about the link between HPV and cervical cancer while one-third of them knew that the vaccine should be administered to the children before they become sexually active. Nevertheless, vaccine acceptance was high if it was offered for free: 76.9% for the bivalent and 74.4% for the quadrivalent vaccine. The proportion of respondents who were willing to copay for the vaccine if it was not totally free was also high, ranging from 68.9% for the bivalent to 67.3% for the quadrivalent vaccine. No significant difference between bivalent and quadrivalent vaccines in terms of prevalence of acceptance and willingness to pay was found. About one-third of the participants, who were willing to copay for the vaccine if it was not offered for free, indicated that they would copay less than 500 baht (30 baht = approx US$1) for three doses of bivalent vaccine. Conclusions: Substantial effort should be made to educate parents prior to introduction of a national HPV vaccination program. In terms of acceptance, either bivalent or quadrivalent vaccines can be recommended.