Genetic Immunization

This book presents the critical information attendant to developing vaccines using the genetic basis of immunology. The authors explore which techniques and experimental paths can be pursued so that efficacious results in human trials can be reasonably expected for the treatment of bacterial, fungal, viral, and autoimmune diseases, as well as cancers. A chapter on the genetic vaccination of neonates with virus or plasmid DNA is also included.

Approaches for Development of New Vaccines

1

(10)

Introduction

1

(1)

First Generation of Vaccines

2

(2)

Second Generation of Vaccines

4

(7)

Recombinant Protein Vaccines

5

(1)

Recombinant Vector Vaccines

5

(1)

Peptide-Based Vaccines

6

(1)

T-Cells Vaccines

7

(1)

DNA Vaccines

7

(4)

Genetic Vaccination: Routes and Formulations

11

(14)

Genetic Vaccines: Vectors

11

(3)

Administration of Genetic Vaccines

14

(3)

Formulations

17

(8)

Intrinsic Adjuvant Properties of Plasmid DNA

25

(10)

Introduction

25

(1)

Immunostimulatory Sequences of Plasmid DNA

26

(1)

Effect of ISS on Cells Involved in Innate Immunity

27

(1)

Effect of ISS on B-Cells

28

(1)

Effect of ISS on T-Cells

29

(1)

Effect of ISS on Cytokine Production

29

(2)

CpG ODN-Induced Synthesis of Cytokines by CD4 T-Cells

30

(1)

CpG ODN Induces the Secretion of IL-4 by B-Cells

30

(1)

Effect of CpG ODN on Production of Cytokines by Antigen-Presenting Cells

31

(1)

Mechanisms of Lymphocyte Activation by CpG ODN

31

(4)

Cellular Mechanisms Involved in the Immune Response Elicited by Genetic Immunization

35

(16)

Introduction

35

(1)

Cellular Uptake of DNA

36

(1)

Cellular Mechanisms Involved in the Immune Response Induced by Intradermal Genetic Immunization

37

(6)

Cellular Mechanisms Involved in the Immune Response Induced by Intramuscular Genetic Immunization

43

(8)

Protective Immune Responses Elicited by Genetic Immunization against Viruses

51

(34)

Introduction

51

(3)

Immune Responses against RNA Viruses Elicited by Genetic Immunization

54

(20)

Negative Sense Single-Stranded RNA Viruses

54

(2)

Genetic Immunization against Influenza Virus

56

(3)

Genetic Immunization against Paramyxoviridae

59

(3)

Genetic Immunization against Other Single-Stranded RNA Viruses of Negative Sense

62

(2)

Genetic Vaccination against Single-Stranded RNA Viruses of Positive Sense

64

(1)

Genetic Immunization against Flaviviridae

64

(2)

Genetic Immunization against Other Single-Stranded RNA Viruses of Positive Sense

66

(1)

Genetic Immunization against Rotaviruses

67

(1)

Genetic Immunization against Retroviruses

68

(6)

Immune Responses against DNA Viruses Elicited by Genetic Immunization

74

(7)

Genetic Vaccination against Hepadnaviridae

75

(2)

Genetic Vaccination against Herpesviridae

77

(3)

Genetic Vaccination against Papillomavirus

80

(1)

Immune Response Triggered by DNA Immunization Against Nonconventional Viruses

81

(1)

Conclusions and Perspectives

82

(3)

Immune Responses Elicited by Genetic Immunization with Bacterial, Fungal, or Parasitic Antigens

85

(14)

DNA-Based Immunization with Bacterial or Fungal Antigens

85

(5)

Immunization with Plasmids Expressing Mycobacteria Antigens

86

(2)

Immunization with Plasmids Expressing Antigens from Other Bacteria or Fungi

88

(2)

DNA-Based Immunization with Parasitic Antigens

90

(6)

Immunization with Plasmids Expressing Antigens from the Genus Plasmodium

90

(4)

DNA Vaccination against Other Parasites

94

(2)

Conclusions and Perspectives

96

(3)

Autoimmunity, Allergy, and Genetic Vaccines

99

(10)

Bacterial DNA: Antigen and Immune Modulator

99

(1)

DNA Vaccines in Allergic Conditions

100

(1)

DNA Vaccination against Autoimmune Diseases

101

(4)

DNA Vaccines and Immune-Mediated Pathology

105

(2)

Conclusions and Perspectives

107

(2)

Genetic Immunization against Tumors

109

(12)

Immunity against Tumors

109

(2)

Strategies to Elicit or Enhance Tumor-Specific Immunity by Nucleic-Acid-Based Delivery of Tumor Antigens

111

(6)

Genetic Immunization with Expression Vectors Encoding Tumor Idiotypes

112

(1)

Genetic Immunization with Expression Vectors Encoding Other Tumor-Derived Antigens

113

(2)

Genetic Immunization against Oncogenic Viruses

115

(1)

Genetic Immunization in Tumor Models Comprising Surrogate Tumor Antigens

116

(1)

Induction or Enhancement of Tumor-Specific Immunity by Nucleic-Acid-Mediated Delivery of Cytokines or Other Immune Stimulators

117

(2)

Conclusions and Perspectives

119

(2)

Genetic Vaccination of Neonates

121

(54)

Characteristics of the Neonatal Immune System

121

(5)

Effects of Neonatal Genetic Immunization

126

(9)

Humoral Responses

127

(2)

CTL Responses

129

(2)

Cytokine Response

131

(1)

Augmentation of Protective Defensive Reactions by Coimmunization of Neonates with Plasmids Encoding Antigens Expressing Epitopes Recognized by B- and T-Cells

132

(3)

Effect of Maternal Antibodies on Immune Response of Neonates and Infants

135

(4)

Protective Ability of Maternal Antibodies

135

(1)

Regulatory Properties of Maternal Antibodies via Idiotype Interactions

136

(1)

Inhibitory Effect of Maternal Antibodies

137

(1)

Inhibitory Effect of Maternal Antibodies on Vaccination of Infants

138

(1)

Effect of Maternal Antibodies on Immune Response of Offspring Born to Dams Immunized with Virus or Plasmid DNA

139

(1)

Effect of Maternal Antibodies on the Immune Response of Young and Adult Animals Elicited by Genetic Immunization

140

(35)

Index

175

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