Animal models and the development of an HIV vaccine

Journal of AIDS and Clinical Research

Volumn 3, Issue SPL ISSUE8, 2012, Pages

  Greek, Ray ^a  

^a Americans For Medical Advancement   (United States)

Author keywords

AIDS; Animal model; Biological complexity; Evolution; HIV; Predictive models; Vaccines

Indexed keywords

EID: 84871753759     PISSN: None     EISSN: 21556113     Source Type: Journal    
DOI: 10.4172/2155-6113.S8-001     Document Type: Article

References (224)

1. Gamble LJ, Matthews QL (2010) Current progress in the development of a prophylactic vaccine for HIV-1. Drug Des Devel Ther 5: 9-26.
2. (2007) Cold shower for AIDS vaccines. Nat Med 13: 1389-1390.
3. Baroncelli S, Negri DRM, Michelini Z, Cara A (2008) Macaca mulatta, fascicularis and nemestrina in AIDS vaccine development. Expert Rev Vaccines 7: 1419-1434.
4. Buchbinder SP, Mehrotra DV, Duerr A, Fitzgerald DW, Mogg R, et al. (2008) Efficacy assessment of a cell-mediated immunity HIV-1 vaccine (the Step Study): a double-blind, randomised, placebo-controlled, test-of-concept trial. Lancet 372: 1881-1893.
5. Shiver JW, Fu TM, Chen L, Casimiro DR, Davies ME, et al. (2002) Replication-incompetent adenoviral vaccine vector elicits effective anti-immunodeficiency-virus immunity. Nature 415: 331-335.
6. Sekaly RP (2008) The failed HIV Merck vaccine study: a step back or a launching point for future vaccine development? J Exp Clin Med 205: 7-12.
7. Robb ML (2008) Failure of the Merck HIV vaccine: an uncertain step forward. Lancet 372: 1857-1858.
8. Stump DS, Vandewoude S (2007) Animal models for HIV AIDS: a comparative review. Comp Med 57: 33-43.
9. Gao F, Bailes E, Robertson DL, Chen Y, Rodenburg CM, et al. (1999) Origin of HIV-1 in the chimpanzee Pan troglodytes troglodytes. Nature 397: 436-441.
10. Plantier JC, Leoz M, Dickerson JE, De Oliveira F, Cordonnier F, et al. (2009) A new human immunodeficiency virus derived from gorillas. Nat Med 15: 871-872.
11. Hirsch VM, Olmsted RA, Murphey-Corb M, Purcell RH, Johnson PR (1989) An African primate lentivirus (SIVsm) closely related to HIV-2. Nature 339: 389-392.
12. Gao F, Yue L, White AT, Pappas PG, Barchue J, et al. (1992) Human infection by genetically diverse SIVSM-related HIV-2 in west Africa. Nature 358: 495-499.
13. Heeney JL, Dalgleish AG, Weiss RA (2006) Origins of HIV and the evolution of resistance to AIDS. Science 313: 462-466.
14. Bozek K, Lengauer T (2010) Positive selection of HIV host factors and the evolution of lentivirus genes. BMC Evol Biol 10: 186.
15. Johnson BK, Stone GA, Godec MS, Asher DM, Gajdusek DC, et al. (1993) Long-term observations of human immunodeficiency virus-infected chimpanzees. AIDS Res Hum Retroviruses 9: 375-378.
16. Nath BM, Schumann KE, Boyer JD (2000) The chimpanzee and other non-human-primate models in HIV-1 vaccine research. Trends Microbiol 8: 426-431.
17. Mccune JM, Namikawa R, Shih CC, Rabin L, Kaneshima H (1990) Suppression of HIV infection in AZT-treated SCID-hu mice. Science 247: 564-566.
18. Baenziger S, Tussiwand R, Schlaepfer E, Mazzucchelli L, Heikenwalder M, et al. (2006) Disseminated and sustained HIV infection in CD34+ cord blood cell-transplanted Rag2-/-gamma c-/-mice. Proc Natl Acad Sci U S A 103: 15951-15956.
19. Gardner MB, Luciw PA (1989) Animal models of AIDS. FASEB J 3: 2593-2606.
20. Mosier DE, Gulizia RJ, Baird SM, Wilson DB, Spector DH, et al. (1991) Human immunodeficiency virus infection of human-PBL-SCID mice. Science 251: 791-794.
21. Shedlock DJ, Silvestri G, Weiner DB (2009) Monkeying around with HIV vaccines: using rhesus macaques to define 'gatekeepers' for clinical trials. Nat Rev Immunol 9: 717-728.
22. Estaquier J, Idziorek T, De Bels F, Barre-Sinoussi F, Hurtrel B, et al. (1994) Programmed cell death and AIDS: significance of T-cell apoptosis in pathogenic and nonpathogenic primate lentiviral infections. Proc Natl Acad Sci U S A 91: 9431-9435.
23. Gougeon ML, Lecoeur H, Boudet F, Ledru E, Marzabal S, et al. (1997) Lack of chronic immune activation in HIV-infected chimpanzees correlates with the resistance of T cells to Fas/Apo-1 (CD95)-induced apoptosis and preservation of a T helper 1 phenotype. J Immunol 158: 2964-2976.
24. Koopman G, Haaksma AG, Ten Velden J, Hack CE, Heeney JL (1999) The relative resistance of HIV type 1-infected chimpanzees to AIDS correlates with the maintenance of follicular architecture and the absence of infiltration by CD8+ cytotoxic T lymphocytes. AIDS Res Hum Retroviruses 15: 365-373.
25. Schuitemaker H, Meyaard L, Kootstra NA, Dubbes R, Otto SA, et al. (1993) Lack of T cell dysfunction and programmed cell death in human immunodeficiency virus type 1-infected chimpanzees correlates with absence of monocytotropic variants. J Infect Dis 168: 1140-1147.
26. Zarling JM, Ledbetter JA, Sias J, Fultz P, Eichberg J, et al. (1990) HIV-infected humans, but not chimpanzees, have circulating cytotoxic T lymphocytes that lyse uninfected CD4+ cells. J Immunol 144: 2992-2998.
27. Nara P, Hatch W, Kessler J, Kelliher J, Carter S (1989) The biology of human immunodeficiency virus-1 IIIB infection in the chimpanzee: in vivo and in vitro correlations. J Med Primatol 18: 343-355.
28. Ferrari G, Ottinger J, Place C, Nigida SM Jr, Arthur LO, et al. (1993) The impact of HIV-1 infection on phenotypic and functional parameters of cellular immunity in chimpanzees. AIDS Res Hum Retroviruses 9: 647-656.
29. Fultz PN (1991) Human immunodeficiency virus infection of chimpanzees: An animal model for asymptomatic HIV carriers and vaccine efficacy. In: Koff W, Wong-Staal F, Kennedy R (eds) AIDS Research Reviews. Marcel Dekker, New York.
30. Fultz PN (1993) Nonhuman primate models for AIDS. Clin Infect Dis 17 Suppl 1: S230-235.
31. Koch JA, Ruprecht RM (1992) Animal models for anti-AIDS therapy. Antiviral Res 19: 81-109.
32. Silvestri G, Paiardini M, Pandrea I, Lederman MM, Sodora DL (2007) Understanding the benign nature of SIV infection in natural hosts. J Clin Invest 117: 3148-3154.
33. Grimaldi LM, Murthy KK, Martino G, Furlan R, Franciotta D, et al. (1996) An immunovirological study of central nervous system involvement during HIV-1 infection of chimpanzees. J Acquir Immune Defic Syndr Hum Retrovirol 13: 12-17.
34. Turner CR, Breslow R, Conklyn MJ, Andresen CJ, Patterson DK, et al. (1996) In vitro and in vivo effects of leukotriene B4 antagonism in a primate model of asthma. J Clin Invest 97: 381-387.
35. Hogan MB, Harris KE, Protter AA, Patterson R (1997) A bradykinin antagonist inhibits both bradykinin-and the allergen-induced airway response in primates. Proc Assoc Am Physicians 109: 269-274.
36. Coleman RA (1999) Current animal models are not predictive for clinical asthma. Pulm Pharmacol Ther 12: 87-89.
37. Reimann KA, Li JT, Veazey R, Halloran M, Park IW, et al. (1996) A chimeric simian/human immunodeficiency virus expressing a primary patient human immunodeficiency virus type 1 isolate env causes an AIDS-like disease after in vivo passage in rhesus monkeys. J Virol 70: 6922-6928.
38. Nishimura Y, Igarashi T, Donau OK, Buckler-White A, Buckler C, et al. (2004) Highly pathogenic SHIVs and SIVs target different CD4+ T cell subsets in rhesus monkeys, explaining their divergent clinical courses. Proc Natl Acad Sci USA 101: 12324-12329.
39. Johnston MI (2000) The role of nonhuman primate models in AIDS vaccine development. Mol Med Today 6: 267-270.
40. Vodros D, Fenyo EM (2004) Primate models for human immunodeficiency virus infection. Evolution of receptor use during pathogenesis. Acta Microbiol Immunol Hung 51: 1-29.
41. Le Rouzic E, Benichou S (2005) The Vpr protein from HIV-1: distinct roles along the viral life cycle. Retrovirology 2: 11.
42. Harouse JM, Gettie A, Tan RC, Blanchard J, Cheng-Mayer C (1999) Distinct pathogenic sequela in rhesus macaques infected with CCR5 or CXCR4 utilizing SHIVs. Science 284: 816-819.
43. Braun SE, Johnson RP (2006) Setting the stage for bench-to-bedside movement of anti-HIV RNA inhibitors-gene therapy for AIDS in macaques. Front Biosci 11: 838-851.
44. Vandewoude S, Apetrei C (2006) Going wild: lessons from naturally occurring T-lymphotropic lentiviruses. Clin Microbiol Rev 19: 728-762.
45. Williams R, Bokhari S, Silverstein P, Pinson D, Kumar A, et al. (2008) Nonhuman primate models of NeuroAIDS. J Neurovirol 14: 292-300.
46. Mckenna P, Hoffmann C, Minkah N, Aye PP, Lackner A, et al. (2008) The macaque gut microbiome in health, lentiviral infection, and chronic enterocolitis. PLoS pathogens 4: e20.
47. Hvilsom C, Carlsen F, Siegismund HR, Corbet S, Nerrienet E, et al. (2008) Genetic subspecies diversity of the chimpanzee CD4 virus-receptor gene. Genomics 92: 322-328.
48. Fomsgaard A, Hirsch VM, Johnson PR (1992) Cloning and sequences of primate CD4 molecules: diversity of the cellular receptor for simian immunodeficiency virus/human immunodeficiency virus. Eur J Immunol 22: 2973-2981.
49. Fu W, Sanders-Beer BE, Katz KS, Maglott DR, Pruitt KD, et al. (2009) Human immunodeficiency virus type 1, human protein interaction database at NCBI. Nucleic Acids Res 37: D417-422.
50. Kim N, Dabrowska A, Jenner RG, Aldovini A (2007) Human and simian immunodeficiency virus-mediated upregulation of the apoptotic factor TRAIL occurs in antigen-presenting cells from AIDS-susceptible but not from AIDS-resistant species. J Virol 81: 7584-7597.
51. Stansell E, Desrosiers RC (2010) Functional contributions of carbohydrate on AIDS virus glycoprotein. Yale J Biol Med 83: 201-208.
52. Zhang YW, Ryder OA, Zhang YP (2003) Intra-and Interspecific Variation of the CCR5 Gene in Higher Primates. Mol Biol Evol 20: 1722-1729.
53. Staprans SI, Feinberg MB (2004) The roles of nonhuman primates in the preclinical evaluation of candidate AIDS vaccines. Expert Rev Vaccines 3: S5-32.
54. Degenhardt JD, De Candia P, Chabot A, Schwartz S, Henderson L, et al. (2009) Copy Number Variation of CCL3-like Genes Affects Rate of Progression to Simian-AIDS in Rhesus Macaques (Macaca mulatta). PLoS Genet 5: e1000346.
55. Xu H, Wang X, Morici LA, Pahar B, Veazey RS (2011) Early Divergent Host Responses in SHIVsf162P3 and SIVmac251 Infected Macaques Correlate with Control of Viremia. PLoS ONE 6: e17965.
56. Silvestri G (2008) AIDS pathogenesis: a tale of two monkeys. J Med Primatol 37 Suppl 2: 6-12.
57. Dias AS, Bester MJ, Britz RF, Apostolides Z (2006) Animal models used for the evaluation of antiretroviral therapies. Curr HIV Res 4: 431-446.
58. Hutchison AT, Schmitz JE, Miller CJ, Sastry KJ, Nehete PN, et al. (2011) Increased inherent intestinal granzyme B expression may be associated with SIV pathogenesis in Asian non-human primates. J Med Primatol 40: 414-426.
59. Batten CJ, De Rose R, Wilson KM, Agy MB, Chea S, et al. (2006) Comparative evaluation of simian, simian-human, and human immunodeficiency virus infections in the pigtail macaque (Macaca nemestrina) model. AIDS Res Hum Retroviruses 22: 580-588.
60. Siber GR, Santosham M, Reid GR, Thompson C, Almeido-Hill J, et al. (1990) Impaired antibody response to Haemophilus influenzae type b polysaccharide and low IgG2 and IgG4 concentrations in Apache children. N Engl J Med 323: 1387-1392.
61. Ward J, Brenneman G, Letson GW, Heyward WL (1990) Limited efficacy of a Haemophilus influenzae type b conjugate vaccine in Alaska Native infants. The Alaska H. influenzae Vaccine Study Group. N Engl J Med 323: 1393-1401.
62. Santosham M, Rivin B, Wolff M, Reid R, Newcomer W, et al. (1992) Prevention of Haemophilus influenzae type b infections in Apache and Navajo children. J Infect Dis 165 Suppl 1: S144-S151.
63. Black FL, Hierholzer W, Woodall JP, Pinhiero F (1971) Intensified reactions to measles vaccine in unexposed populations of american Indians. J Infect Dis 124: 306-317.
64. Poland GA, Ovsyannikova IG, Jacobson RM (2008) Vaccine immunogenetics: bedside to bench to population. Vaccine 26: 6183-6188.
65. Cook IF (2008) Sexual dimorphism of humoral immunity with human vaccines. Vaccine 26: 3551-3555.
66. Edwards KM, Burns VE, Allen LM, Mcphee JS, Bosch JA, et al. (2007) Eccentric exercise as an adjuvant to influenza vaccination in humans. Brain Behav Immun 21: 209-217.
67. Engler RJ, Nelson MR, Klote MM, Vanraden MJ, Huang CY, et al. (2008) Half-vs full-dose trivalent inactivated influenza vaccine (2004-2005): age, dose, and sex effects on immune responses. Arch Intern Med 168: 2405-2414.
68. Cook IF, Barr I, Hartel G, Pond D, Hampson AW (2006) Reactogenicity and immunogenicity of an inactivated influenza vaccine administered by intramuscular or subcutaneous injection in elderly adults. Vaccine 24: 2395-2402.
69. Klein SL, Jedlicka A, Pekosz A (2010) The Xs and Y of immune responses to viral vaccines. Lancet Infect Dis 10: 338-349.
70. Jacobson RM, Poland GA (2004) The genetic basis for measles vaccine failure. Acta Paediatr Suppl 93: 43-46.
71. Poland GA, Ovsyannikova IG, Jacobson RM, Smith DI (2007) Heterogeneity in vaccine immune response: the role of immunogenetics and the emerging field of vaccinomics. Clin Pharmacol Ther 82: 653-664.
72. Poland GA, Ovsyannikova IG, Jacobson RM, Vierkant RA, Jacobsen SJ, et al. (2001) Identification of an association between HLA class II alleles and low antibody levels after measles immunization. Vaccine 20: 430-438.
73. Jacobson RM, Poland GA, Vierkant RA, Pankratz VS, Schaid DJ, et al. (2003) The association of class I HLA alleles and antibody levels after a single dose of measles vaccine. Hum Immunol 64: 103-109.
74. Poland GA, Ovsyannikova IG, Jacobson RM (2008) Immunogenetics of seasonal influenza vaccine response. Vaccine 26 Suppl 4: D35-40.
75. Ovsyannikova IG, Jacobson RM, Dhiman N, Vierkant RA, Pankratz VS, et al. (2008) Human leukocyte antigen and cytokine receptor gene polymorphisms associated with heterogeneous immune responses to mumps viral vaccine. Pediatrics 121: e1091-1099.
76. Dhiman N, Ovsyannikova IG, Vierkant RA, Ryan JE, Pankratz VS, et al. (2008) Associations between SNPs in toll-like receptors and related intracellular signaling molecules and immune responses to measles vaccine: preliminary results. Vaccine 26: 1731-1736.
77. Ovsyannikova IG, Jacobson RM, Vierkant RA, Shane Pankratz V, Jacobsen SJ, et al. (2004) Associations between human leukocyte antigen (HLA) alleles and very high levels of measles antibody following vaccination. Vaccine 22: 1914-1920.
78. Ovsyannikova IG, Jacobson RM, Vierkant RA, Jacobsen SJ, Pankratz VS, et al. (2004) The contribution of HLA class I antigens in immune status following two doses of rubella vaccination. Hum Immunol 65: 1506-1515.
79. Dhiman N, Poland GA, Cunningham JM, Jacobson RM, Ovsyannikova IG, et al. (2007) Variations in measles vaccine-specific humoral immunity by polymorphisms in SLAM and CD46 measles virus receptors. J Allergy Clin Immunol 120: 666-672.
80. Yucesoy B, Johnson VJ, Fluharty K, Kashon ML, Slaven JE, et al. (2009) Influence of cytokine gene variations on immunization to childhood vaccines. Vaccine 27: 6991-6997.
81. King C (2009) Personalised vaccines could protect all children New Scientist: 11.
82. Thomas C, Moridani M (2010) Interindividual variations in the efficacy and toxicity of vaccines. Toxicology 278: 204-210.
83. Ovsyannikova IG, Dhiman N, Jacobson RM, Poland GA (2006) Human leukocyte antigen polymorphisms: variable humoral immune responses to viral vaccines. Expert Rev Vaccines 5: 33-43.
84. Klein S, Huber S (2010) Sex differences in susceptibility to viral infection. In: Klein S, Roberts C (eds) Sex hormones and immunity to infection. Springer-Verlag, Berlin: 93-122.
85. Anker M (2007) Addressing sex and gender in epidemic-prone infectious diseases. In:World Health Organization Press, Geneva.
86. Theiler RN, Rasmussen SA, Treadwell TA, Jamieson DJ (2008) Emerging and zoonotic infections in women. Infect Dis Clin North Am 22: 755-772.
87. Holden C (2005) Sex and the suffering brain. Science 308: 1574.
88. Kaiser J (2005) Gender in the pharmacy: does it matter? Science 308: 1572.
89. Macdonald JS (2002) Vive la difference: sex and fluorouracil toxicity. J Clin Oncol 20: 1439-1441.
90. Meier A, Chang JJ, Chan ES, Pollard RB, Sidhu HK, et al. (2009) Sex differences in the Toll-like receptor-mediated response of plasmacytoid dendritic cells to HIV-1. Nat Med 15: 955-959.
91. Schenkman L (2010) Random Samples. 3Qs. Science 330: 737.
92. Sloan JA, Goldberg RM, Sargent DJ, Vargas-Chanes D, Nair S, et al. (2002) Women experience greater toxicity with fluorouracil-based chemotherapy for colorectal cancer. J Clin Oncol 20: 1491-1498.
93. Wald C, Wu C (2010) Biomedical research Of Mice and Women: The Bias in Animal Models. Science 327: 1571-1572.
94. Willyard C (2009) HIV gender clues emerge. Nat Med 15: 830.
95. Simon V (2005) Wanted: women in clinical trials. Science 308: 1517.
96. Amend K, Hicks D, Ambrosone CB (2006) Breast cancer in African-American women: differences in tumor biology from European-American women. Cancer Res 66: 8327-8330.
97. Cheung DS, Warman ML, Mulliken JB (1997) Hemangioma in twins. Ann Plast Surg 38: 269-274.
98. Couzin J (2007) Cancer research. Probing the roots of race and cancer. Science 315: 592-594.
99. Couzin J (2007) Human genetics. In Asians and whites, gene expression varies by race. Science 315: 173-174.
100. Foulkes AS, Wohl DA, Frank I, Puleo E, Restine S, et al. (2006) Associations among race/ethnicity, ApoC-III genotypes, and lipids in HIV-1-infected individuals on antiretroviral therapy. PLoS Med 3: e52.
101. Gregor Z, Joffe L (1978) Senile macular changes in the black African. Br J Ophthalmol 62: 547-550.
102. Spielman RS, Bastone LA, Burdick JT, Morley M, Ewens WJ, et al. (2007) Common genetic variants account for differences in gene expression among ethnic groups. Nat Genet 39: 226-231.
103. Haiman CA, Stram DO, Wilkens LR, Pike MC, Kolonel LN, et al. (2006) Ethnic and racial differences in the smoking-related risk of lung cancer. N Engl J Med 354: 333-342.
104. Tan PL, Jacobson RM, Poland GA, Jacobsen SJ, Pankratz VS (2001) Twin studies of immunogenicity--determining the genetic contribution to vaccine failure. Vaccine 19: 2434-2439.
105. Newport MJ, Goetghebuer T, Marchant A (2005) Hunting for immune response regulatory genes: vaccination studies in infant twins. Expert Rev Vaccines 4: 739-746.
106. Poland GA, Ovsyannikova IG, Jacobson RM (2009) Application of pharmacogenomics to vaccines. Pharmacogenomics 10: 837-852.
107. Bruder CE, Piotrowski A, Gijsbers AA, Andersson R, Erickson S, et al. (2008) Phenotypically concordant and discordant monozygotic twins display different DNA copy-number-variation profiles. Am J Hum Genet 82: 763-771.
108. Dempster EL, Pidsley R, Schalkwyk LC, Owens S, Georgiades A, et al. (2011) Disease-associated epigenetic changes in monozygotic twins discordant for schizophrenia and bipolar disorder. Hum Mol Genet 20: 4786-4796.
109. Fraga MF, Ballestar E, Paz MF, Ropero S, Setien F, et al. (2005) Epigenetic differences arise during the lifetime of monozygotic twins. Proc Natl Acad Sci U S A 102: 10604-10609.
110. Javierre BM, Fernandez AF, Richter J, Al-Shahrour F, Martin-Subero JI, et al. (2010) Changes in the pattern of DNA methylation associate with twin discordance in systemic lupus erythematosus. Genome Res 20: 170-179.
111. Wong AH, Gottesman II, Petronis A (2005) Phenotypic differences in genetically identical organisms: the epigenetic perspective. Hum Mol Genet 1: R11-18.
112. Davies G, Genini S, Bishop SC, Giuffra E (2009) An assessment of opportunities to dissect host genetic variation in resistance to infectious diseases in livestock. Animal 3: 415-436.
113. Leach R, Craigmile S, Knott S, Williams J, Glass E (2010) Quantitative trait loci for variation in immune response to a Foot-and-Mouth Disease virus peptide. BMC Genetics 11: 107.
114. Murphy PM (1993) Molecular mimicry and the generation of host defense protein diversity. Cell 72: 823-826.
115. Kimman TG, Vandebriel RJ, Hoebee B (2007) Genetic variation in the response to vaccination. Community Genet 10: 201-217.
116. Hennig BJ, Fielding K, Broxholme J, Diatta M, Mendy M, et al. (2008) Host genetic factors and vaccine-induced immunity to hepatitis B virus infection. PLoS ONE 3: e1898.
117. Hennig BJ, Hall AJ (2010) Host genetic factors in hepatitis B infection, liver cancer and vaccination response: A review with a focus on Africa. Sci Total Environ.
118. Newport MJ, Goetghebuer T, Weiss HA, Whittle H, Siegrist CA, et al. (2004) Genetic regulation of immune responses to vaccines in early life. Genes Immun 5: 122-129.
119. Van Loveren H, Van Amsterdam JG, Vandebriel RJ, Kimman TG, Rumke HC, et al. (2001) Vaccine-induced antibody responses as parameters of the influence of endogenous and environmental factors. Environ Health Perspect 109: 757-764.
120. Sutter RW, Patriarca PA, Suleiman AJM, Pallansch MA, Zell ER, et al. (1993) Paralytic Poliomyelitis in Oman: Association between Regional Differences in Attack Rate and Variations in Antibody Responses to Oral Poliovirus Vaccine. Int J Epidemiol 22: 936-944.
121. Lafollette H, Shanks N (1996) Brute Science: Dilemmas of animal experimentation. Routledge, London and New York.
122. Greek R, Shanks N (2009) FAQs About the Use of Animals in Science: A handbook for the scientifically perplexed. University Press of America, Lanham.
123. Greek R, Greek J (2010) Is the use of sentient animals in basic research justifiable? Philos Ethics Humanit Med 5: 14.
124. Kornberg A (1995) Science in the stationary phase. Science 269: 1799.
125. House of Commons Select Committee on Science and Technology (2007) Blue Skies Research Tenth Report. In:House of Commons. Session 2006-2007.
126. Organisation for Economic Cooperation and Development (1963) The Measurement of Scientific and Technical activities: Proposed Standard Practice for Surveys of Research and Development. In, Paris.
127. National Environment Research Council (2007) Blue Skies Review Final Report. In:NERC, London.
128. Braben D (2004) Pioneering Research: A Risk Worth Taking. John Wiley and Sons, New Jersey.
129. Lord Rayleigh (1942) The Life of Sir J.J. Thomson. Cambridge University Press.
130. Bernard C (1973) An Introduction to the Study of Experimental Medicine. Dover, New York.
131. Ilar (2004) Science, Medicine, and Animals. National Academies Press.
132. Takahashi M (2000) Development of a live varicella vaccine--past and future. Jpn J Infect Dis 53: 47-55.
133. Science AaFTaO (2011) Q & A on Evolution and Intelligent Design. American Association for the Advancement of Science.
134. Committee on Revising Science and Creationism (2008) Science, Evolution, and Creationism. National Academy of Sciences, Washington DC.
135. Litchfield JT Jr (1962) Symposium on clinical drug evaluation and human pharmacology. XVI. Evaluation of the safety of new drugs by means of tests in animals. Clin Pharmacol Ther 3: 665-672.
136. Dixon RL (1972) Toxicology of environmental agents: a blend of applied and basic research. Environ Health Perspect 2: 103-116.
137. Fletcher AP (1978) Drug safety tests and subsequent clinical experience. J R Soc Med 71: 693-696.
138. Heywood R (1981) Target organ toxicity. Toxicol Lett 8: 349-358.
139. Heywood R (1983) Target organ toxicity II. Toxicol Lett 18: 83-88.
140. Salsburg D (1983) The lifetime feeding study in mice and rats--an examination of its validity as a bioassay for human carcinogens. Fundam Appl Toxicol 3: 63-67.
141. Sietsema WK (1989) The absolute oral bioavailability of selected drugs. Int J Clin Pharmacol Ther Toxicol 27: 179-211.
142. Heywood R (1990) Clinical Toxicity--Could it have been predicted? Post-marketing experience. In: CE Lumley, Walker S (eds) Animal Toxicity Studies: Their Relevance for Man. Quay, Lancaster, p 57-67.
143. Suter K (1990) What can be learned from case studies? The company approach. In: Lumley C, Walker S (eds) Animal Toxicity Studies: Their Relevance for Man. Quay, Lancaster, p 71-78.
144. Igarashi T (1994) The duration of toxicity studies required to support repeated dosing in clinical investigation-A toxicologists opinion. In: C Parkinson NM, C Lumley, SR Walker (ed) CMR Workshop: The Timing of Toxicological Studies to Support Clinical Trials. Kluwer, Boston/UK, p 67-74.
145. Kiem HP (2011) CCR5 targeting to control HIV/SHIV to nonhuman primates. Fred Hutchinson Cancer Research Center. NIAID $276,808.
146. Friedrich TC (2010) Defining The Importance Of CD8+ T Cell Breadth In SIV/HIV Protective Immunity. University Of Wisconsin Madison.
147. Norris KA (2011) Vaccine strategies against pneumocystis in non-human primates. Louisiana State Univ HSC New Orleans. National Heart, Lung, And Blood Institute.
148. Dinh MH (2010) Characterizing the role of male circumcision in HIV sexual transmission. Northwestern University At Chicago. Eunice Kennedy Shriver National Institute Of Child Health & Human Development. $126,963.
149. Abel K (2009) A rhesus macaque model of siv-malaria co-infection. University of California Davis.
150. Ahmed R (2011) Role of follicular t helper cells in enhancing humoral immunity and protection. Emory University. NIAID.
151. Gauduin MC (2011) TB Infection In NHP Model Of Pediatric AIDS. Texas Biomedical Research Institute. National Center For Research Resources.
152. Shanks N, Greek R (2009) Animal Models in Light of Evolution. Brown Walker, Boca Raton.
153. Freeman M, St Johnston D (2008) Wherefore DMM? Disease Models & Mechanisms 1: 6-7.
154. Moynihan R, Bero L, Ross-Degnan D, Henry D, Lee K, et al. (2000) Coverage by the news media of the benefits and risks of medications. N Engl J Med 342: 1645-1650.
155. Anonymous (2000) Drug Cheerleaders. New Scientist:19.
156. (2007) Beyond interferon. Nat Biotechnol 25: 1375.
157. Connor S, Green C (2008) Is it time to give up the search for an AIDS vaccine? The Independent.
158. Corey L, Nabel GJ, Dieffenbach C, Gilbert P, Haynes BF, et al. (2011) HIV-1 vaccines and adaptive trial designs. Sci Transl Med 3: 79.
159. Letvin NL (2009) Virology. Moving forward in HIV vaccine development. Science 326: 1196-1198.
160. Thomas C (2009) Roadblocks in HIV research: five questions. Nat Med 15: 855-859.
161. Watkins DI, Burton DR, Kallas EG, Moore JP, Koff WC (2008) Nonhuman primate models and the failure of the Merck HIV-1 vaccine in humans. Nat Med 14: 617-621.
162. Check E (2004) HIV vaccine research a shot in the arm for immunologists. Nat Med 10: 1268.
163. Le Grand R, Clayette P, Noack O, Vaslin B, Theodoro F, et al. (1994) An animal model for antilentiviral therapy: effect of zidovudine on viral load during acute infection after exposure of macaques to simian immunodeficiency virus. AIDS Res Hum Retroviruses 10: 1279-1287.
164. Mofenson LM (1997) Reducing the risk of perinatal HIV-1 transmission with zidovudine: results and implications of AIDS Clinical Trials Group protocol 076. Acta paediatr Suppl 421: 89-96.
165. Gaschen B, Taylor J, Yusim K, Foley B, Gao F, et al. (2002) Diversity considerations in HIV-1 vaccine selection. Science 296: 2354-2360.
166. Sokoloff B (1952) Cancer: New Approaches, New Hope. Devin-Adair Co.
167. Beniashvili DS (1994) Experimental Tumors in Monkeys. CRC Press.
168. Steinberg D (2002) Companies Halt First Alzheimer Vaccine Trial. At issue: What inflamed patients' brains? The Scientist 16: 22.
169. Marwick C (2000) Promising vaccine treatment for Alzheimer disease found. JAMA 284: 1503-1505.
170. Weiss R (2002) Alzheimer's Vaccine Permanently Shelved. The Washington Post.
171. Manson JM (1987) Biological Considerations for Risk Assessment in Developmental Toxicology. In: McLachlan JA, Pratt RM, Markert CL (eds) Developmental Toxicology: Mechanisms and Risks. Banbury Report 26. Cold Springs Harbor Laboratory, p 307-322.
172. Uberla K (2005) Efficacy of AIDS vaccine strategies in nonhuman primates. Med Microbiol Immunol 194: 201-206.
173. Feinberg MB, Moore JP (2002) AIDS vaccine models: challenging challenge viruses. Nat Med 8: 207-210.
174. Gura T (1997) Systems for identifying new drugs are often faulty. Science 278: 1041-1042.
175. Paul JR (1971) A History of Poliomyelitis. Yale University Press, New Haven.
176. Oshinsky DM (2005) Polio: An American Story. Oxford University Press.
177. Horstmann DM (1985) The Poliomyelitis Story: a scientific hegira. Yale J Biol Med 58: 79-90.
178. Gershon AA (2001) Live-attenuated varicella vaccine. Infect Dis Clin North Am 15: 65-81.
179. Mueller NH, Gilden DH, Cohrs RJ, Mahalingam R, Nagel MA (2008) Varicella Zoster Virus Infection: Clinical Features, Molecular Pathogenesis of Disease, and Latency. Neurologic clinics 26: 675-697.
180. Van Regenmortel MH (2004) Reductionism and complexity in molecular biology. Scientists now have the tools to unravel biological complexity and overcome the limitations of reductionism. EMBO Rep 5: 1016-1020.
181. Shanks N, Greek R, Greek J (2009) Are animal models predictive for humans? Philos Ethics Humanit Med 4: 2.
182. Gerhart J, Kirschner M (2007) The Theory of Facilitated Variation. In: Avise JC, Ayala FJ (eds) In the Light of Evolution: Volume 1. Adaptation and Complex Design. National Acdemy of Sciences, Washington DC, p 45-64.
183. Kirschner MW, Gerhart JC, Norton J (2006) The Plausibility of Life. Yale University Press.
184. Thornton SP (1998) Background of Incisional Refractive Surgery. In: Wu H, Thompson V, Steinert R, Hersh P, Slade S (eds) Refractive Surgery. Thieme, New York, p 127-134.
185. Sato T (1939) Treatment of the conical cornea. Acta Soc Ophthalmol Jpn: 544-555.
186. Sato T (1951) Posterior half-corneal incision for myopia (animal experiments). Acta Soc Ophthalmol Jpn 55: 219.
187. Sato T, Akiyama K, Shibata H (1953) A new surgical approach to myopia. Am J Ophthalmol 36: 823-829.
188. Kanai A, Yamaguchi T, Yajima Y, Funahashi M, Nakajima A (1979) The fine structure of bullous keratopathy after anteroposterior incision of the cornea for myopia. Folia Ophthalmol Jpn 30: 841.
189. (1981) Radial keratotomy. Am J Ophthalmol 92: 286-295.
190. Akiyama K, Tanaka M, Kanai A, Nakajima A (1984) Problems arising from Sato's radial keratotomy in Japan. CLAO J 10: 179-184.
191. Holland J (1999) Emergence. Perseus Publishing.
192. Van Regenmortel MH (2004) Biological complexity emerges from the ashes of genetic reductionism. J Mol Recognit 17: 145-148.
193. Van Regenmortel MH (2002) Pitfalls of Reductionism in Immunology. In: van Regenmortel MHV, Hull D (eds) Promises and Limits of Reductionism in the Biomedical Sciences. John Wiley & Sons LTD, Chichester, p 47-66.
194. Van Regenmortel MH (2002) Reductionism and the search for structure-function relationships in antibody molecules. J Mol Recognit 15: 240-247.
195. Csete ME, Doyle JC (2002) Reverse engineering of biological complexity. Science 295: 1664-1669.
196. Kitano H (2002) Computational systems biology. Nature 420: 206-210.
197. Morange M (2001) A successful form for reductionism. The Biochemist 23: 37-39.
198. Morange M (2001) The misunderstood gene. Harvard University Press, Cambridge.
199. Alm E, Arkin AP (2003) Biological networks. Curr Opin Struct Biol 13: 193-202.
200. Novikoff AB (1945) The Concept of Integrative Levels and Biology. Science 101: 209-215.
201. Mayr E (1998) This Is Biology: The Science of the Living World. Belknap Press.
202. Darlison MG, Pahal I, Thode C (2005) Consequences of the evolution of the GABA(A) receptor gene family. Cell Mol Neurobiol 25: 607-624.
203. Enna SJ, Williams M (2009) Defining the role of pharmacology in the emerging world of translational research. Adv Pharmacol 57: 1-30.
204. Geerts H (2009) Of mice and men: bridging the translational disconnect in CNS drug discovery. CNS Drugs 23: 915-926.
205. Jankovic J, Noebels JL (2005) Genetic mouse models of essential tremor: are they essential? J Clin Invest 115: 584-586.
206. Kieburtz K, Olanow CW (2007) Translational experimental therapeutics: The translation of laboratory-based discovery into disease-related therapy. Mt Sinai J Med 74: 7-14.
207. Liu Z, Maas K, Aune TM (2004) Comparison of differentially expressed genes in T lymphocytes between human autoimmune disease and murine models of autoimmune disease. Clin Immunol 112: 225-230.
208. Gabor Miklos GL (2005) The human cancer genome project--one more misstep in the war on cancer. Nat Biotechnol 23: 535-537.
209. Froehlich TE, Epstein JN, Nick TG, Melguizo Castro MS, Stein MA, et al. (2011) Pharmacogenetic Predictors of Methylphenidate Dose-Response in Attention-Deficit/Hyperactivity Disorder. Journal of the American Academy of Child and Adolescent Psychiatry 50: 1129-1139.
210. Hudson KL (2011) Genomics, Health Care, and Society. N Engl J Med 365: 1033-1041.
211. Serrano D, Lazzeroni M, Zambon CF, Macis D, Maisonneuve P, et al. (2011) Efficacy of tamoxifen based on cytochrome P450 2D6, CYP2C19 and SULT1A1 genotype in the Italian Tamoxifen Prevention Trial. Pharmacogenomics J 11: 100-107.
212. Tonks A (2007) Quest for the AIDS vaccine. BMJ 334: 1346-1348.
213. Ledford H (2008) Translational research: the full cycle. Nature 453: 843-845.
214. Maclennan, Amos (1990) Cosmetics and Toiletries Manufacturers and Suppliers. Clinical Sciences Research Ltd XVII: 24.
215. Horrobin DF (2003) Modern biomedical research: an internally self-consistent universe with little contact with medical reality? Nat Rev Drug Discov 2: 151-154.
216. Altman L (1998) Who Goes First? The Story of Self-Experimentation in Medicine. University of California Press.
217. Okulicz JF, Marconi VC, Landrum ML, Wegner S, Weintrob A, et al. (2009) Clinical outcomes of elite controllers, viremic controllers, and long-term nonprogressors in the US Department of Defense HIV natural history study. J Infect Dis 200: 1714-1723.
218. Hutter G, Nowak D, Mossner M, Ganepola S, Mussig A, et al. (2009) Long-term control of HIV by CCR5 Delta32/Delta32 stem-cell transplantation. N Engl J Med 360: 692-698.
219. Singh A, Singh UP, Varma A, Verma AS (2011) Cure for HIV: New possibility on horizon. J Pharm Bioallied Sci 3: 461-464.
220. Van Regenmortel MH (2012) Requirements for empirical immunogenicity trials, rather than structure-based design, for developing an effective HIV vaccine. Arch Virol 157: 1-20.
221. Van Regenmortel MH (2011) Two meanings of reverse vaccinology and the empirical nature of vaccine science. Vaccine 29: 7875.
222. Van Regenmortel MH (2011) Limitations to the structure-based design of HIV-1 vaccine immunogens. J Mol Recognit 24: 741-753.
223. Van Regenmortel MHV (1999) Molecular design versus empirical discovery in peptide-based vaccines. Coming to terms with fuzzy recognition sites and ill-defined structure-function relationships in immunology. Vaccine 18: 216-221.
224. Maugh Ii TH, Chong JR (2006) AIDS Stalks Humans as HIV Research Slows to a Crawl. In: LA Times. June 4.