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Evaluation of Porcine Circovirus type 2 vaccine

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dc.contributor.advisor채찬희-
dc.contributor.author서휘원-
dc.date.accessioned2017-07-13T16:42:34Z-
dc.date.available2017-07-13T16:42:34Z-
dc.date.issued2014-02-
dc.identifier.other000000018790-
dc.identifier.urihttps://hdl.handle.net/10371/120195-
dc.description학위논문 (박사)-- 서울대학교 대학원 : 수의학과, 2014. 2. 채찬희.-
dc.description.abstractPorcine circovirus type 2 (PCV2) is one of the most important swine infectious pathogen which cause a variety of swine diseases called porcine circovirus associated diseases (PCVAD) such as postweaning multisystemic wasting syndrome (PMWS), porcine respiratory disease complex (PRDC), porcine dermatitis, nephropathy syndrome (PDNS), and reproductive associated disorder.Vaccination against PCV2 is nowdays the most effective tool for preventing the PCVAD. Since the first PCV2 vaccine was introduced in 2004, the six commercial PCV2 vaccine have been registered worldwide up to date. These vaccines were largely classified in inactivated whole virus vaccine, capsid protein recombinant vaccine, and chimeric PCV1/PCV2 vaccine according to antigen types.
The objectives of these studies were to evaluate the PCV2 vaccines based on clinical, virological, immunological, and pathological analyses and investigate the difference of efficacy among the vaccines. The experimental challenge study with a reformulated inactivated chimeric PCV1-2 vaccine was perfomed for 42 days to investigate the vaccine efficacy about humoral and cell-mediated immunity. Vaccinated challenged animals had a significantly lower number of genomic copies of PCV2 in the blood than non-vaccinated challenged animals at 14 and 28 days post challenge (dpc
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dc.description.abstractP < 0.001). The percentage of viremic pigs was significantly lower in vaccinated challenged animals compared to non-vaccinated challenged animals (P < 0.05). The Neutralizing antibody (NA) titers were significantly higher in vaccinated challenged and vaccinated non-challenged animals than in non-vaccinated challenged animals at 0, 14, and 28 dpc. The mean numbers of PCV2-specific IFN-r-SCs were significantly higher in vaccinated challenged and vaccinated non-challenged animals compared to non-vaccinated challenged animals at 0 and 14 dpc(P < 0.05). The vaccinated animals displayed significantly greater PCV2-specific DTH responses than the non-vaccinated animals (P < 0.01). The results of the present study demonstrated the protective immunity induced by the reformulated inactivated chimeric PCV1-2 vaccine correlated with the reduction of PCV2 viremia.
The efficacy of the reformulated inactivated chimeric PCV 1-2 vaccine was evaluated under field conditions. Three farms were selected based on their history of postweaning multisystemic wasting syndrome (PMWS). On each farm, a total of 50 3-week-old pigs were randomly allocated to one of two treatment groups: (i) vaccinated at 3 weeks of age and (ii) non-vaccinated. In case of field trial, it is most important to investigate for vaccine efficacy of economical aspects. Clinical examination indicated that vaccinated animals displayed an improved average daily weight gain (ADWG) (+47.3 grams/day
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dc.description.abstractP < 0.05) and a reduced time to market (-6 days-
dc.description.abstractP < 0.05). Virological and pathological examinations indicated that vaccinated animals displayed a reduced PCV2 viremia and associated lesion compared to non-vaccinated animals. Immunological examination indicated that vaccinated animals induced PCV2-specific NAs and IFN-r-SCs. The vaccine not only successfully induced the humoral and cell-mediated immune response but also improved the average daily weight gain which is criteria for vaccine efficacy of production improvement.
Studies for comparion of PCV2 vaccines efficacy were performed to investigate different level of immune responses induced by 4 commercial vaccines. These studies were divided by two experiments. The objective of first experiment was to compare the vaccines without challenge for investigating a tendancy of vaccines such as duration of persistent efficacy and time to indicate the peak level of efficacy. Inactivated chimeric PCV1-2 vaccines induced higher levels of PCV2-specific NAs and IFN-r-SCs in pigs than did the other 3 commercial PCV2 vaccines. The proportions of CD4+ cells were significantly higher in animals vaccinated with inactivated whole virus and chimeric PCV 1-2 vaccines than in animals vaccinated with the 2 subunit vaccines. Maximal induction of cell-mediated immunity is reached at 21 days post vaccination (dpv), whereas maximal induction of humoral immunity is reached at 42 dpv in all four vaccines.
In second experiment, protective efficacy induced by pcv2 vaccines were compared through a challenge of single PCV2. The groups vaccinated with inactivated whole virus and chimeric PCV 1-2 vaccines exhibited significantly higher NA titers, number of IFN-r-SCs, and proportion of CD4+ lymphocytes than the other 2 vaccinated groups (P < 0.05). The groups vaccinated with inactivated whole virus and chimeric PCV 1-2 vaccines reduced significantly more viral load in blood than another subunit vaccine group (P < 0.05). These studies demonstrated that the different types of antigens in the 4 commercial single-dose PCV2 vaccines induce different levels of protective immune responses.
The effects of PCV2 vaccines on PCV2 virus in experimentally infected boars were evaluated and compared based on virus shedding in semen. In the first experiment, the vaccinated group were immunized with an inactivated PCV2 vaccine at a 3-week interval, and then, 3 weeks after the second vaccination, the boars were intranasally inoculated with PCV2b. Serum and semen samples were collected for 60 dpc. The number of PCV2 genome copies of PCV2 in the serum and semen were significantly lower in vaccinated challenged boars than in non-vaccinated challenged boars at 7 to 60 dpc (P < 0.05). In the second experiment, efficacy of three commercial vaccines were compared in boars for 70 dpc. Serum and semen samples from the group vaccinated with chimeric PCV 1-2 vaccine had significantly decreased PCV2 genomic copy numbers compared with the goup vaccinated with subunit vaccine at 21 and 28 dpc (P < 0.05). Consequently, the vaccination protocol reduced the amount of PCV2 DNA shed in the semen. However, there was a significantly different amount of PCV2 DNA shed in semen among the 3 vaccinated groups.
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dc.description.tableofcontentsTABLE OF CONTENTS

ABSTRACT...........................................................................................................................I
CONTENTS.........................................................................................................................V
LIST OF TABLES...............................................................................................................X
LIST OF FIGURES...........................................................................................................XI
LIST OF ABBREVIATIONS........................................................................................XIII
GENERAL INTRODUCTION...........................................................................................1
LITERATURE REVIEW....................................................................................................4
1. Porcine Circovirus type 2..................................................................................................................4
1.1. Historical background………...........……………………………………..………………4
1.2. Genome organization……………………………...................................................................5
1.3. Replication dynamics............................................................................................6
1.4. Classfication of genotype………………....................................................................7
2. Porcine circovirus associated diseases (PCVAD) ..……………………………………………..8
2.1. Post-weaning multisystemic wasting syndrome (PMWS)...............................................8
2.2. Porcine resiratory disease complex (PRDC)....................................................................9
2.3. Porcine dermatitis nephritic syndrome (PDNS)……...……………………….....9
3. Pathogenesis……………………………………………………………………………………….10
3.1. Experimental reproduction………………….………………………………..……………10
3.2. Microscopic lesions and antigen amounts in lymphoid………………..……………12
3.3. PCV2 replication and its target cells………………………………………..……………12
4. Transmission of PCV2…………………..………………………..……………………………….13
3.1. Horizontal transmission………………….………………………………..……………13
3.2. Vertical transmission………………………………..….............................................14
5. Immunology……………………………………………….…………………………15
5.1. Humoral immunity to PCV2……………………..…….……..……..………15
5.2. Immunodepression in clinical PMWS………………………………………….16
5.3. Protein and cytokine expression in PMWS……………………………………………17
5.4. Interaction between PCV2 and immune cells in vitro…………………………......18
5.5. Cellular immune responses……........................……………………………......19
6. PCV2 Vaccines…….………………………………………………………………………....21
6.1. Commercial PCV2 vaccines…………………………………………………………21
6.2. Strategies and efficacy of PCV2 vaccines………………………………………22
7. References…………………………………………………………………………...23

PART I. Evaluation of a reformulated inactivated chimeric PCV1-2 vaccine based on clinical, virological, pathological and immunological examination under experimental and field conditions

Chapter 1. Reduction of porcine circovirus type 2 (PCV2) viremia by a reformulated inactivated chimeric PCV1-2 vaccine-induced humoral and cellular immunity after experimental PCV2 challenge…………………………………………….…………………………………….38

Abstract…………………………………………………………………………………...39
Introduction………………………………………………………………………………40
Materials and Methods…………………………………………………………………..42
Results…………………………………………………………………………………….46
Discussion………………………………………………………………………………56
References……………………………………………………………………………..58

Chapter 2. Efficacy of a reformulated inactivated chimeric PCV1-2 vaccine based on clinical, virological, pathological and immunological examination under field conditions
…………………………………………………….……………………..………………………….62

Abstract…………………………………………………………………………………...63
Introduction………………………………………………………………………………64
Materials and Methods…………………………………………………………………..65
Results…………………………………………………………………………………….69
Discussion………………………………………………………………………………79
References……………………………………………………………………………..81



PART II. Comparison of immune responses and protective efficacy induced by porcine circovirus type 2 (PCV2) vaccines

Chapter 1. Antigenic types contribute to elicit different levels of humoral and cell-mediated immune responses among commercial single-dose porcine circovirus type 2 vaccines………..84

Abstract………………………………………………………………………………….85
Introduction……………………………………………………………………………..86
Materials and Methods…………………………………………………………………88
Results…………………………………………………………………………………...91
Discussion………………………………………………………………………………..97
References……………………………………………………………………………….100

Chapter 2. Comparison of four commercial one-dose porcine circovirus type 2 vaccines based on clinical, virological, immunological and pathological evaluation……………...……………..104

Abstract………………………………………………………………………………….105
Introduction……………………………………………………………………………..106
Materials and Methods…………………………………………………………………108
Results…………………………………………………………………………………...112
Discussion………………………………………………………………………………..124
References……………………………………………………………………………….127

PART III. Effects of porcine circovirus type 2 (PCV2) vaccines on PCV2 virus shedding in semen from experimentally infected boars

Chapter 1. Effects of an inactivated porcine circovirus type 2 (PCV2) vaccine on PCV2 virus shedding in semen from experimentally infected boars…………………………………………132

Abstract………………………………………………………………………………….133
Introduction……………………………………………………………………………..134
Materials and Methods…………………………………………………………………135
Results…………………………………………………………………………………...138
Discussion………………………………………………………………………………..144
References……………………………………………………………………………….147

Chapter 2. Comparison of three commercial one-dose porcine circovirus type 2 (PCV2) vaccines on PCV2 shedding in semen from experimentally infected boars………………...……………..150

Abstract………………………………………………………………………………….151
Introduction……………………………………………………………………………..152
Materials and Methods…………………………………………………………………153
Results…………………………………………………………………………………...155
Discussion………………………………………………………………………………..159
References……………………………………………………………………………….161
Abstract in Korean…………………………………………………………………………….…...164
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dc.formatapplication/pdf-
dc.format.extent2314971 bytes-
dc.format.mediumapplication/pdf-
dc.language.isoen-
dc.publisher서울대학교 대학원-
dc.subjectPorcine circovirus type 2-
dc.subjectPorcine circovirus-associated disease-
dc.subjectPostweaning multisystemic wasting syndrome-
dc.subjectCommercial porcine circovirus type 2 vaccines-
dc.subjectVaccine efficacy-
dc.subjectSemen-
dc.subject.ddc636-
dc.titleEvaluation of Porcine Circovirus type 2 vaccine-
dc.typeThesis-
dc.description.degreeDoctor-
dc.citation.pages165-
dc.contributor.affiliation수의과대학 수의학과-
dc.date.awarded2014-02-
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