Immunotherapy for Infectious Diseases

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Principles of Vaccine Development 139 that attenuated Salmonella organisms recovered from immunized animals lose the plasmid of avirulence or the foreign gene. 3. Finally, it should colonize to allow for a continuous synthesis of foreign protein. Recombinant Salmonella vectors can be administered orally and therefore are able to induce mucosal immunity. Recombinant BCG Vectors Recombinant BCG vector vaccines were obtained by transfer of replicative or integrative plasmids by electroporation, gene replacement, plasmid conjugation, and phage lysogeny (15). These vectors are able to induce a long-lasting humoral and cellular immunity conferred by the expression of foreign gene and by the nature of the BCG vector, respectively. Bacillus anthracis (Stern strain) B. anthracis (non-pathogenic Stern strain) was used to express foreign genes. This strain contains a pX01 gene coding for toxin but lacks pX02 plasmid coding for capsular polysaccharide, which is responsible for virulence. A vector expressing the listeriolysine gene was able to deliver Listeria protein to the cytoplasm and to induce a CTL response mediated by CD8 T-cells (16). DNA Vaccines The utilization of DNA as a vaccine is based on the fact that the injection of a plasmid bearing a reporter gene leads to in vivo transfection of cells as well as to transcription of the foreign gene inserted into plasmid (17). There has been an explosion of research in this area, leading to human trials of DNA vaccines. DNA vaccines are constructed by insertion into plasmid of a foreign gene and a strong promoter, which ensures a high level of expression of the antigen gene, bearing protective epitopes. Recent studies have established the best conditions for constructing the plasmids used for vaccination. The spacing required between the regulatory and inserted genes, the stability of RNA transcripts, and the minimum number of copies required for a significant synthesis of foreign antigen able to induce immune responses have also been studied. Table 6 lists the systems in which DNA vaccination against viruses, bacteria, and parasites were assessed. Immunity The induction of a humoral immune response depends on the type of protein encoded by the foreign gene. Whereas a protein bearing epitopes recognized by a B-cell will induce the synthesis of antibodies, a protein expressing CD8 T-cell epitopes induces a CTL response. In the case of the humoral immune response, the B-cells can recognize the conformational or linear epitopes on the surface of antigens secreted by transfected cells. In contrast, in the case of CD8 T-cells, the peptides required for activation of CTL precursors are generated via endogenous pathways, and the class I-peptide complexes translocated on the membrane are recognized by T-cells. The CD4 T-cells are stimulated by in vivo transfected APCs, which synthesize the protein, process it, and present the peptides in association with class II molecules to CD4 T-cells. Recent reports showed that both macrophages (18) and dendritic cells (19) are transfected in vivo and are able to activate the CD4 T-cells
140 Bona Table 6 DNA Vaccines Used in Experimental Models Microbe Virus Negative-strand RNA viruses Influenza Measles Newcastle Sendai Bovine respiratory syncytial Rabies Lymphocytic choriomeningitis Ebola Positive, single-strand RNA viruses Hepatitis C St. Louis encephalitis Tick-borne encephalitis Japanese encephalitis Russian-spring encephalitis Bovine viral diarrhea Infectious bronchitis Foot and mouth disease Double-strand RNA Rotavirus Retroviruses Human, simian, and feline immunodeficiency Human T-cell leukemia/lymphoma Cas murine leukemia DNA viruses Hepatitis B Bovine herpes Herpes simplex Cytomegalovirus Pseudorabies Papilloma Advantages Several advantages have made genetic immunization appealing for vaccination: 1. The DNA vaccine is very stable and easy to manufacture; it is easy to construct new plasmids in the case of vaccines against microbes exhibiting natural genetic variation. 2. Long-lasting persistence of plasmid and sustained synthesis of low doses of antigen preclude induction of high-dose tolerance and favor the generation of memory cells. 3. Lack of contaminant proteins in plasmid preparation prevents side effects such as allergic reactions. 4. DNA immunization does not require adjuvants since the plasmids rich in CpG motifs are endowed with intrinsic adjuvanticity. 5. It can induce humoral and cellular immune responses. 6. It can prime neonates, which may lead to development of vaccines for neonates or infants otherwise unresponsive to inactivated or live attenuated vaccines. Disadvantages Various studies have demonstrated the safety of DNA vaccines. However, DNA vaccination has two possible drawbacks: first, the induction of anti-DNA antibodies and second, the possibility of integration of plasmid into the host genome by non-homolo-
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Immunotherapy for Infectious Diseas
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In f e c t i o u s . D i s e a s e
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© 2002 Humana Press Inc. 999 River
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vi Preface I am grateful to all of
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viii Contents 11 Passive Immunother
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x Contributors BARBARA G. MATTHEWS,
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From: Immunotherapy for Infectious
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Humoral Immunity 5 Fig. 1. Humoral
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Humoral Immunity 7 Table 1 Properti
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Humoral Immunity 9 minal complement
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Humoral Immunity 11 ficity. In ligh
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Humoral Immunity 13 Fig. 7. VDJ joi
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Humoral Immunity 15 Fig. 9. Messeng
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Humoral Immunity 17 In contrast to
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Humoral Immunity 19 advantage to tr
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Humoral Immunity 21 32. Allman DM,
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Some Basic Cellular Immunology Prin
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Cellular Immunology Principles 25 i
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Cellular Immunology Principles 27 s
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Cellular Immunology Principles 29 d
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Cellular Immunology Principles 31 f
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Cellular Immunology Principles 33 F
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Cellular Immunology Principles 35 R
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Cellular Immunology Principles 37 1
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INTRODUCTION Immune Defense at Muco
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Immune Defense at Mucosal Surfaces
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II Molecular Basis for Immunotherap
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64 Kunert and Katinger IMMUNOGLOBUL
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66 Fig. 2. Monomeric, dimeric, and
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68 Kunert and Katinger Fig. 4. Humo
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70 Kunert and Katinger remove prote
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72 Kunert and Katinger Fig. 6. Diff
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74 Kunert and Katinger persons of a
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76 Kunert and Katinger that so-call
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78 Kunert and Katinger whereas sele
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80 Kunert and Katinger Different pr
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82 Kunert and Katinger HUMAN/MOUSE
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84 Kunert and Katinger are expresse
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86 Kunert and Katinger missing meta
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Page 107 and 108: 96 Kunert and Katinger 117. Wright
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Page 112 and 113: Dendritic Cells 101 several organis
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Page 120 and 121: Dendritic Cells 109 complete tumor
Page 122 and 123: Dendritic Cells 111 19. Holland SM,
Page 124 and 125: Dendritic Cells 113 mouse pneumonit
Page 126 and 127: Dendritic Cells 115 dendritic cells
Page 128 and 129: INTRODUCTION Cytokines, Cytokine An
Page 130 and 131: Cytokines, Cytokine Antagonists, an
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Page 162 and 163: INTRODUCTION Immunopathogenesis of
Page 164 and 165: Immunopathogenesis of HIV Disease 1
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Page 175 and 176: 164 Connick counts ranged from 73 t
Page 177 and 178: 166 Connick retinitis in an individ
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Page 183 and 184: 172 Connick 2. Delta Coordinating C
Page 185 and 186: 174 Connick 39. Hurni MA, Bohlen L,
Page 187 and 188: 176 Connick 76. Dolan M.J., Clerici
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Active Immunization for HIV Infecti
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200 Jacobson changes of gp120 alter
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202 Jacobson is reduced (54,55). A
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204 Jacobson Table 2 Potential Prot
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206 Jacobson from the SIV/17E-Cl-in
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208 Jacobson Several groups have de
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210 Jacobson HUMAN STUDIES Polyclon
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212 Jacobson clinical isolates, whi
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214 Jacobson 22. Beasley RP, Hwang
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216 Jacobson 59. Yoshiyama H, Mo H,
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218 Jacobson 95. Prince AM, Reesink
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220 Jacobson 133. Stiehm ER, Lamber
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222 Kilby and Bucy Although clinica
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224 Kilby and Bucy can infect human
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226 Kilby and Bucy the proinflammat
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228 Kilby and Bucy CD3/CD28, and th
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230 Kilby and Bucy of viral replica
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232 Kilby and Bucy 21. Cao Y, Qin L
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234 Kilby and Bucy 64. Pantaleo G,
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236 Kilby and Bucy 101. Clements-Ma
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238 Dornburg and Pomerantz cells (5
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240 Dornburg and Pomerantz Fig. 2.
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242 Dornburg and Pomerantz domains
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244 Dornburg and Pomerantz GENETIC
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246 Dornburg and Pomerantz Fig. 5.
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248 Dornburg and Pomerantz 6. Balti
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Viral Infections Other than HIV 253
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Virus-Associated Malignancies 261 c
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Virus-Associated Malignancies 263 o
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Virus-Associated Malignancies 265 I
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Virus-Associated Malignancies 267 R
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Virus-Associated Malignancies 269 T
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Virus-Associated Malignancies 271 1
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Virus-Associated Malignancies 273 5
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Bacterial Infections and Sepsis 277
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284 Wallis and Johnson replication
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286 Wallis and Johnson Several stud
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288 Wallis and Johnson monocytes, a
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290 Wallis and Johnson peripheral b
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292 Wallis and Johnson (A. Hise and
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294 Wallis and Johnson infections,
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296 Wallis and Johnson 37. Boom WH.
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298 Wallis and Johnson 77. Ellner J
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300 Wallis and Johnson 113. Raad I,
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302 Wallis and Johnson 154. Anonymo
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304 Table 1 Major Fungal Infections
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306 Casadevall species suggest that
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308 Casadevall transfusions from G-
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310 Casadevall Table 3 Augmentation
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312 Casadevall There has been some
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314 Casadevall effective in achievi
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316 Casadevall CONCLUSION AND FUTUR
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318 Casadevall 16. Boutati EI, Anai
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320 Casadevall 52. Gallin JI, Malec
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322 Casadevall 91. Kowanko IC, Ferr
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324 Index Blastomycosis, see Fungal
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326 Index C-type retrovirus vectors
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328 Index K Klebsiella, intravenous
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330 Index Vaccine Recombinant vecto
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Infectious Disease IMMUNOTHERAPY FO
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