Prospects for oral replicating adenovirus-vectored vaccines

Vaccine

Volumn 31, Issue 32, 2013, Pages 3236-3243

  Deal, Cailin ^a   Pekosz, Andrew ^a   Ketner, Gary ^a  

^a JOHNS HOPKINS BLOOMBERG SCHOOL OF PUBLIC HEALTH   (United States)

Author keywords

Capsid display; Hexon; Oral administration; Replicating adenovirus vectors; Vaccine

Indexed keywords

ADENOVIRUS VACCINE; ADENOVIRUS VECTOR; ANTIGEN; ANTIGENIC EPITOPE; EPITOPE; HEPATITIS B SURFACE ANTIGEN; HEPATITIS B VACCINE; IMMUNOGLOBULIN G1 ANTIBODY; IMMUNOGLOBULIN G2A ANTIBODY; OUTER MEMBRANE PROTEIN F; POLYPEPTIDE; UNCLASSIFIED DRUG; VIRUS VACCINE;

ACUTE RESPIRATORY TRACT DISEASE; AMINO ACID SEQUENCE; ANTIBODY TITER; ARMY; CELLULAR IMMUNITY; CRYSTAL STRUCTURE; DRUG DELIVERY SYSTEM; DRUG EFFICACY; DRUG SAFETY; GENE EXPRESSION; GENE VECTOR; HUMAN; HUMORAL IMMUNITY; IMMUNE RESPONSE; IMMUNE SYSTEM; IMMUNIZATION; IMMUNOGENICITY; NONHUMAN; NUCLEOTIDE SEQUENCE; PRIORITY JOURNAL; PSEUDOMONAS AERUGINOSA; REVIEW; SEROTYPE; TRANSGENE; VIRAL RESPIRATORY TRACT INFECTION; VIREMIA; VIRUS CAPSID; VIRUS IMMUNITY; VIRUS PARTICLE; VIRUS REPLICATION; VIRUS SHEDDING; X RAY CRYSTALLOGRAPHY;

ADENOVIRIDAE; ADMINISTRATION, ORAL; ANIMALS; ANTIGENS; CAPSID; CAPSID PROTEINS; CLINICAL TRIALS AS TOPIC; EPITOPES; GENETIC VECTORS; HUMANS; IMMUNITY, CELLULAR; IMMUNITY, HUMORAL; TRANSGENES; VACCINES; VACCINES, SYNTHETIC; VIRUS REPLICATION;

EID: 84879459516     PISSN: 0264410X     EISSN: 18732518     Source Type: Journal    
DOI: 10.1016/j.vaccine.2013.05.016     Document Type: Review

References (98)

1. Bourinbaiar A.S., Metadilogkul O., Jirathitikal V. Mucosal AIDS vaccines. Viral Immunol 2003, 16(4):427-445.
2. Silin D.S., Lyubomska O.V., Jirathitikal V., Bourinbaiar A.S. Oral vaccination: where we are?. Expert Opin Drug Deliv 2007, 4(4):323-340.
3. FDA Complete List of Vaccines Licensed for Immunization and Distribution in the United States 2013, Available from, [cited 26.04.13]. http://www.fda.gov/BiologicsBloodVaccines/default.htm.
4. Lycke N. Recent progress in mucosal vaccine development: potential and limitations. Nat Rev Immunol 2012, 12(8):592-605.
5. Takafuji E.T., Gaydos J.C., Allen R.G., Top F.H. Simultaneous administration of live, enteric-coated adenovirus types 4, 7 and 21 vaccines: safety and immunogenicity. J Infect Dis 1979, 140(1):48-53.
6. Schwartz A.R., Togo Y., Hornick R.B. Clinical evaluation of live, oral types 1, 2, and 5 adenovirus vaccines. Am Rev Respir Dis 1974, 109(2):233-239.
7. Gutekunst R.R., White R.J., Edmondson W.P., Chanock R.M. Immunization with live type 4 adenovirus: determination of infectious virus dose and protective effect of enteric infection. Am J Epidemiol 1967, 86(2):341-349.
8. Top F.H., Buescher E.L., Bancroft W.H., Russell P.K. Immunization with live types 7 and 4 adenovirus vaccines, II. Antibody response and protective effect against acute respiratory disease due to adenovirus type 7. J Infect Dis 1971, 124(2):155-160.
9. Lyons A., Longfield J., Kuschner R., Straight T., Binn L., Seriwatana J., et al. A double-blind, placebo-controlled study of the safety and immunogenicity of live, oral type 4 and type 7 adenovirus vaccines in adults. Vaccine 2008, 26(23):2890-2898.
10. Rollier C.S., Reyes-Sandoval A., Cottingham M.G., Ewer K., Hill A.V. Viral vectors as vaccine platforms: deployment in sight. Curr Opin Immunol 2011, 23(3):377-382.
11. US National Institutes of Health ClinicalTrials.gov 2013, Available from, [cited 01.05.13]. http://www.clinicaltrials.gov/.
12. Lore K., Adams W.C., Havenga M.J., Precopio M.L., Holterman L., Goudsmit J., et al. Myeloid and plasmacytoid dendritic cells are susceptible to recombinant adenovirus vectors and stimulate polyfunctional memory T cell responses. J Immunol 2007, 179(3):1721-1729.
13. Patterson L.J., Kuate S., Daltabuit-Test M., Li Q., Xiao P., McKinnon K., et al. Replicating adenovirus-simian immunodeficiency virus (SIV) vectors efficiently prime SIV-specific systemic and mucosal immune responses by targeting myeloid dendritic cells and persisting in rectal macrophages, regardless of immunization route. Clin Vaccine Immunol 2012, 19(5):629-637.
14. Small J.C., Ertl H.C. Viruses - from pathogens to vaccine carriers. Curr Opin Virol 2011, 1(4):241-245.
15. Huang M.M., Hearing P. Adenovirus early region 4 encodes two gene products with redundant effects in lytic infection. J Virol 1989, 63(6):2605-2615.
16. Weinberg D.H., Ketner G. Adenoviral early region 4 is required for efficient viral DNA replication and for late gene expression. J Virol 1986, 57(3):833-838.
17. Jones N., Shenk T. Isolation of deletion and substitution mutants of adenovirus type 5. Cell 1978, 13(1):181-188.
18. Sullivan N.J., Sanchez A., Rollin P.E., Yang Z.Y., Nabel G.J. Development of a preventive vaccine for Ebola virus infection in primates. Nature 2000, 408(6812):605-609.
19. Thomas M.A., Spencer J.F., La Regina M.C., Dhar D., Tollefson A.E., Toth K., et al. Syrian hamster as a permissive immunocompetent animal model for the study of oncolytic adenovirus vectors. Cancer Res 2006, 66(3):1270-1276.
20. Pacini D.L., Dubovi E.J., Clyde W.A. A new animal model for human respiratory tract disease due to adenovirus. J Infect Dis 1984, 150(1):92-97.
21. Chengalvala M., Lubeck M.D., Davis A.R., Mizutani S., Molnar-Kimber K., Morin J., et al. Evaluation of adenovirus type 4 and type 7 recombinant hepatitis B vaccines in dogs. Vaccine 1991, 9(7):485-490.
22. Jogler C., Hoffmann D., Theegarten D., Grunwald T., Uberla K., Wildner O., et al. Replication properties of human adenovirus in vivo and in cultures of primary cells from different animal species. J Virol 2006, 80(7):3549-3558.
23. Lubeck M.D., Davis A.R., Chengalvala M., Natuk R.J., Morin J.E., Molnar-Kimber K., et al. Immunogenicity and efficacy testing in chimpanzees of an oral hepatitis B vaccine based on live recombinant adenovirus. Proc Natl Acad Sci U S A 1989, 86(17):6763-6767.
24. Klessig D.F., Grodzicker T. Mutations that allow human Ad2 and Ad5 to express late genes in monkey cells map in the viral gene encoding the 72K DNA binding protein. Cell 1979, 17(4):957-966.
25. Toth K., Spencer J.F., Tollefson A.E., Kuppuswamy M., Doronin K., Lichtenstein D.L., et al. Cotton rat tumor model for the evaluation of oncolytic adenoviruses. Hum Gene Ther 2005, 16(1):139-146.
26. Tacket C.O., Losonsky G., Lubeck M.D., Davis A.R., Mizutani S., Horwith G., et al. Initial safety and immunogenicity studies of an oral recombinant adenohepatitis B vaccine. Vaccine 1992, 10(10):673-676.
27. Kruijer W., van Schaik F.M., Sussenbach J.S. Structure and organization of the gene coding for the DNA binding protein of adenovirus type 5. Nucleic Acids Res 1981, 9(18):4439-4457.
28. Buge S.L., Richardson E., Alipanah S., Markham P., Cheng S., Kalyan N., et al. An adenovirus-simian immunodeficiency virus env vaccine elicits humoral, cellular, and mucosal immune responses in rhesus macaques and decreases viral burden following vaginal challenge. J Virol 1997, 71(11):8531-8541.
29. Buge S.L., Murty L., Arora K., Kalyanaraman V.S., Markham P.D., Richardson E.S., et al. Factors associated with slow disease progression in macaques immunized with an adenovirus-simian immunodeficiency virus (SIV) envelope priming-gp120 boosting regimen and challenged vaginally with SIVmac251. J Virol 1999, 73(9):7430-7440.
30. Zhao J., Lou Y., Pinczewski J., Malkevitch N., Aldrich K., Kalyanaraman V.S., et al. Boosting of SIV-specific immune responses in rhesus macaques by repeated administration of Ad5hr-SIVenv/rev and Ad5hr-SIVgag recombinants. Vaccine 2003, 21(25-26):4022-4035.
31. Malkevitch N., Patterson L.J., Aldrich K., Richardson E., Alvord W.G., Robert-Guroff M. A replication competent adenovirus 5 host range mutant-simian immunodeficiency virus (SIV) recombinant priming/subunit protein boosting vaccine regimen induces broad, persistent SIV-specific cellular immunity to dominant and subdominant epitopes in Mamu-A*01 rhesus macaques. J Immunol 2003, 170(8):4281-4289.
32. Zhao J., Pinczewski J., Gomez-Roman V.R., Venzon D., Kalyanaraman V.S., Markham P.D., et al. Improved protection of rhesus macaques against intrarectal simian immunodeficiency virus SIV(mac251) challenge by a replication-competent Ad5hr-SIVenv/rev and Ad5hr-SIVgag recombinant priming/gp120 boosting regimen. J Virol 2003, 77(15):8354-8365.
33. Gomez-Roman V.R., Grimes G.J., Potti G.K., Peng B., Demberg T., Gravlin L., et al. Oral delivery of replication-competent adenovirus vectors is well tolerated by SIV- and SHIV-infected rhesus macaques. Vaccine 2006, 24(23):5064-5072.
34. Gurwith M., Lock M., Taylor E.M., Ishioka G., Alexander J., Mayall T., et al. Safety and immunogenicity of an oral, replicating adenovirus serotype 4 vector vaccine for H5N1 influenza: a randomised, double-blind, placebo-controlled, phase 1 study. Lancet Infect Dis 2013, 13(3):238-250.
35. Alexander J., Ward S., Mendy J., Manayani D.J., Farness P., Avanzini J.B., et al. Pre-clinical evaluation of a replication-competent recombinant adenovirus serotype 4 vaccine expressing influenza H5 hemagglutinin. PLoS ONE 2012, 7(2):pe31177.
36. Talaat K.R., Karron R.A., Liang P.H., McMahon B.A., Luke C.J., Thumar B., et al. An open-label phase I trial of a live attenuated H2N2 influenza virus vaccine in healthy adults. Influenza Other Respi Viruses 2011, 7(1):66-73.
37. Wold W.S., Doronin K., Toth K., Kuppuswamy M., Lichtenstein D.L., Tollefson A.E. Immune responses to adenoviruses: viral evasion mechanisms and their implications for the clinic. Curr Opin Immunol 1999, 11(4):380-386.
38. Reid T., Galanis E., Abbruzzese J., Sze D., Wein L.M., Andrews J., et al. Hepatic arterial infusion of a replication-selective oncolytic adenovirus (dl1520): phase II viral, immunologic, and clinical endpoints. Cancer Res 2002, 62(21):6070-6079.
39. Small E.J., Carducci M.A., Burke J.M., Rodriguez R., Fong L., van Ummersen L., et al. A phase I trial of intravenous CG7870, a replication-selective, prostate-specific antigen-targeted oncolytic adenovirus, for the treatment of hormone-refractory, metastatic prostate cancer. Mol Ther 2006, 14(1):107-117.
40. Lin S.W., Cun A.S., Harris-McCoy K., Ertl H.C. Intramuscular rather than oral administration of replication-defective adenoviral vaccine vector induces specific CD8+ T cell responses in the gut. Vaccine 2007, 25(12):2187-2193.
41. Shiratsuchi T., Rai U., Krause A., Worgall S., Tsuji M. Replacing adenoviral vector HVR1 with a malaria B cell epitope improves immunogenicity and circumvents preexisting immunity to adenovirus in mice. J Clin Invest 2010, 120(10):3688-3701.
42. Boyer J.L., Sofer-Podesta C., Ang J., Hackett N.R., Chluchlolo M.J., Senina S., et al. Protective immunity against a lethal respiratory Yersinia pestis challenge induced by V antigen or the F1 capsular antigen incorporated into adenovirus capsid. Hum Gene Ther 2010, 21(7):891-901.
43. Worgall S., Krause A., Qiu J., Joh J., Hackett N.R., Crystal R.G. Protective immunity to pseudomonas aeruginosa induced with a capsid-modified adenovirus expressing P. aeruginosa OprF. J Virol 2007, 81(24):13801-13808.
44. van Oostrum J., Burnett R.M. Molecular composition of the adenovirus type 2 virion. J Virol 1985, 56(2):439-448.
45. Rux J.J., Kuser P.R., Burnett R.M. Structural and phylogenetic analysis of adenovirus hexons by use of high-resolution X-ray crystallographic, molecular modeling, and sequence-based methods. J Virol 2003, 77(17):9553-9566.
46. Rux J.J., Burnett R.M. Type-specific epitope locations revealed by X-ray crystallographic study of adenovirus type 5 hexon. Mol Ther 2000, 1(1):18-30.
47. Crawford-Miksza L., Schnurr D.P. Analysis of 15 adenovirus hexon proteins reveals the location and structure of seven hypervariable regions containing serotype-specific residues. J Virol 1996, 70(3):1836-1844.
48. Wu H., Han T., Belousova N., Krasnykh V., Kashentseva E., Dmitriev I., et al. Identification of sites in adenovirus hexon for foreign peptide incorporation. J Virol 2005, 79(6):3382-3390.
49. Matthews Q.L., Yang P., Wu Q., Belousova N., Rivera A.A., Stoff-Khalili M.A., et al. Optimization of capsid-incorporated antigens for a novel adenovirus vaccine approach. Virol J 2008, 5:98.
50. Abe S., Okuda K., Ura T., Kondo A., Yoshida A., Yoshizaki S., et al. Adenovirus type 5 with modified hexons induces robust transgene-specific immune responses in mice with pre-existing immunity against adenovirus type 5. J Gene Med 2009, 11(7):570-579.
51. Bruder J.T., Semenova E., Chen P., Limbach K., Patterson N.B., Stefaniak M.E., et al. Modification of Ad5 hexon hypervariable regions circumvents pre-existing Ad5 neutralizing antibodies and induces protective immune responses. PLoS ONE 2012, 7(4):e33920.
52. Crompton J., Toogood C.I., Wallis N., Hay R.T. Expression of a foreign epitope on the surface of the adenovirus hexon. J Gen Virol 1994, 75(Pt 1):133-139.
53. Worgall S., Krause A., Rivara M., Hee K.K., Vintayen E.V., Hackett N.R., et al. Protection against P. aeruginosa with an adenovirus vector containing an OprF epitope in the capsid. J Clin Invest 2005, 115(5):1281-1289.
54. McConnell M.J., Danthinne X., Imperiale M.J. Characterization of a permissive epitope insertion site in adenovirus hexon. J Virol 2006, 80(11):5361-5370.
55. Palma C., Overstreet M.G., Guedon J.M., Hoiczyk E., Ward C., Karen K.A., et al. Adenovirus particles that display the Plasmodium falciparum circumsporozoite protein NANP repeat induce sporozoite-neutralizing antibodies in mice. Vaccine 2011, 29(8):1683-1689.
56. Tian X., Su X., Li X., Li H., Li T., Zhou Z., et al. Protection against enterovirus 71 with neutralizing epitope incorporation within adenovirus type 3 hexon. PLoS ONE 2012, 7(7):pe41381.
57. Zhou D., Wu T.L., Emmer K.L., Kurupati R., Tuyishime S., Li Y., et al. Hexon-modified recombinant E1-deleted adenovirus vectors as dual specificity vaccine carriers for influenza virus. Mol Ther 2012, 21(3):696-706.
58. Gu L., Li Z.C., Krendelchtchikov A., Krendelchtchikova V., Wu H., Matthews Q.L. Using multivalent adenoviral vectors for HIV vaccination. PLoS ONE 2013, 8(3):e60347.
59. Zubieta C., Schoehn G., Chroboczek J., Cusack S. The structure of the human adenovirus 2 penton. Mol Cell 2005, 17(1):121-135.
60. Krause A., Joh J.H., Hackett N.R., Roelvink P.W., Bruder J.T., Wickham T.J., et al. Epitopes expressed in different adenovirus capsid proteins induce different levels of epitope-specific immunity. J Virol 2006, 80(11):5523-5530.
61. Xia D., Henry L., Gerard R.D., Deisenhofer J. Structure of the receptor binding domain of adenovirus type 5 fiber protein. Curr Top Microbiol Immunol 1995, 199(Pt 1):39-46.
62. Krasnykh V., Dmitriev I., Mikheeva G., Miller C.R., Belousova N., Curiel D.T. Characterization of an adenovirus vector containing a heterologous peptide epitope in the HI loop of the fiber knob. J Virol 1998, 72(3):1844-1852.
63. Lanzi A., Ben Youssef G., Perricaudet M., Benihoud K. Anti-adenovirus humoral responses influence on the efficacy of vaccines based on epitope display on adenovirus capsid. Vaccine 2010, 29(7):1463-1471.
64. Sharma A., Krause A., Xu Y., Sung B., Wu W., Worgall S. Adenovirus-based vaccine with epitopes incorporated in novel fiber sites to induce protective immunity against Pseudomonas aeruginosa. PLoS ONE 2013, 8(2):e56996.
65. Blackwell J.L., Li H., Gomez-Navarro J., Dmitriev I., Krasnykh V., Richter C.A., et al. Using a tropism-modified adenoviral vector to circumvent inhibitory factors in ascites fluid. Hum Gene Ther 2000, 11(12):1657-1669.
66. Dmitriev I., Krasnykh V., Miller C.R., Wang M., Kashentseva E., Mikheeva G., et al. An adenovirus vector with genetically modified fibers demonstrates expanded tropism via utilization of a coxsackievirus and adenovirus receptor-independent cell entry mechanism. J Virol 1998, 72(12):9706-9713.
67. Wickham T.J., Tzeng E., Shears 2nd L.L., Roelvink P.W., Li Y., Lee G.M., et al. Increased in vitro and in vivo gene transfer by adenovirus vectors containing chimeric fiber proteins. J Virol 1997, 71(11):8221-8229.
68. Denby L., Work L.M., Seggem D.J., Wu E., McVey J.H., Nicklin S.A., et al. Development of renal-targeted vectors through combined in vivo phage display and capsid engineering of adenoviral fibers from serotype 19p. Mol Ther 2007, 15(9):1647-1654.
69. McConnell M.J., Imperiale M.J. Biology of adenovirus and its use as a vector for gene therapy. Hum Gene Ther 2004, 15(11):1022-1033.
70. Parks R.J. Adenovirus protein IX: a new look at an old protein. Mol Ther 2005, 11(1):19-25.
71. Li J., Fatima A., Komarova S., Ugai H., Uprety P., Roth J.C., et al. Evaluation of adenovirus capsid labeling versus transgene expression. Virol J 2010, 7:21.
72. Meulenbroek R.A., Sargent K.L., Lunde J., Jasmin B.J., Parks R.J. Use of adenovirus protein IX (pIX) to display large polypeptides on the virion - generation of fluorescent virus through the incorporation of pIX-GFP. Mol Ther 2004, 9(4):617-624.
73. Kimball K.J., Rivera A.A., Zinn K.R., Icyuz M., Saini V., Li J., et al. Novel infectivity-enhanced oncolytic adenovirus with a capsid-incorporated dual-imaging moiety for monitoring virotherapy in ovarian cancer. Mol Imaging 2009, 8(5):264-277.
74. Matthews Q.L., Sibley D.A., Wu H., Li J., Stoff-Khalili M.A., Waehler R., et al. Genetic incorporation of a herpes simplex virus type 1 thymidine kinase and firefly luciferase fusion into the adenovirus protein IX for functional display on the virion. Mol Imaging 2006, 5(4):510-519.
75. Bayer W., Tenbusch M., Lietz R., Johrden L., Schimmer S., Uberla K., et al. Vaccination with an adenoviral vector that encodes and displays a retroviral antigen induces improved neutralizing antibody and CD4+ T-cell responses and confers enhanced protection. J Virol 2010, 84(4):1967-1976.
76. Robert-Guroff M. Replicating and non-replicating viral vectors for vaccine development. Curr Opin Biotechnol 2007, 18(6):546-556.
77. Xiang Z.Q., Gao G.P., Reyes-Sandoval A., Li Y., Wilson J.M., Ertl H.C. Oral vaccination of mice with adenoviral vectors is not impaired by preexisting immunity to the vaccine carrier. J Virol 2003, 77(20):10780-10789.
78. Peters W., Brandi J.R., Lindbloom J.D., Martinez C.J., Scalian C.D., Trager G.R., et al. Oral administration of an adenovirus vector encoding both an avian influenza A hemagglutinin and a TLR3 ligand induces antigen specific granzyme B and IFN-gamma T cell responses in humans. Vaccine 2013, 31(13):1752-1758.
79. Wohlfart C. Neutralization of adenoviruses: kinetics, stoichiometry, and mechanisms. J Virol 1988, 62(7):2321-2328.
80. Xiang Z., Gao G., Reyes-Sandoval A., Cohen C.J., Li Y., Bergelson J.M., et al. Novel, chimpanzee serotype 68-based adenoviral vaccine carrier for induction of antibodies to a transgene product. J Virol 2002, 76(6):2667-2675.
81. Dudareva M., Andrews L., Gilbert S.C., Bejon P., Marsh K., Mwacharo J., et al. Prevalence of serum neutralizing antibodies against chimpanzee adenovirus 63 and human adenovirus 5 in Kenyan children, in the context of vaccine vector efficacy. Vaccine 2009, 27(27):3501-3504.
82. Kahl C.A., Bonnell J., Hiriyanna S., Fultz M., Nyberg-Hoffman C., Chen P., et al. Potent immune responses and in vitro pro-inflammatory cytokine suppression by a novel adenovirus vaccine vector based on rare human serotype 28. Vaccine 2010, 28(35):5691-5702.
83. Blanke C., Clark C., Broun E.R., Tricot G., Cunningham I., Cornetta K., et al. Evolving pathogens in allogeneic bone marrow transplantation: increased fatal adenoviral infections. Am J Med 1995, 99(3):326-328.
84. Baldwin A., Kingham H., Darville M., Foot A.B., Grier D., Cornish J.M., et al. Outcome and clinical course of 100 patients with adenovirus infection following bone marrow transplantation. Bone Marrow Transplant 2000, 26(12):1333-1338.
85. Koopmann J., Dombrowski F., Rockstroh J.K., Pfeifer U., Sauerbruch T., Spengler U. Fatal pneumonia in an AIDS patient coinfected with adenovirus and Pneumocystis carinii. Infection 2000, 28(5):323-325.
86. Khoo S.H., Bailey A.S., de Jong J.C., Mandal B.K. Adenovirus infections in human immunodeficiency virus-positive patients: clinical features and molecular epidemiology. J Infect Dis 1995, 172(3):629-637.
87. Rhoads J.L., Birx D.L., Wright D.C., Brundage J.F., Brandt B.L., Redfield R.R., et al. Safety and immunogenicity of multiple conventional immunizations administered during early HIV infection. J Acquir Immune Defic Syndr 1991, 4(7):724-731.
88. Mueller R.E., Muldoon R.L., Jackson G.G. Communicability of enteric live adenovirus type 4 vaccine in families. J Infect Dis 1969, 119(1):60-66.
89. Stanley E.D., Jackson G.G. Spread of enteric live adenovirus type 4 vaccine in married couples. J Infect Dis 1969, 119(1):51-59.
90. Matthews Q.L., Fatima A., Tang Y., Perry B.A., Tsuruta A., Komarova S., et al. HIV antigen incorporation within adenovirus hexon hypervariable 2 for a novel HIV vaccine approach. PLoS ONE 2010, 5(7):e11815.
91. Flatt J.W., Fox T.L., Makarova N., Blackwell J.L., Dmitriev I.P., Kashentseva E.A., et al. CryoEM visualization of an adenovirus capsid-incorporated HIV antigen. PLoS ONE 2012, 7(11):e49607.
92. Wickham T.J., Roelvink P.W., Brough D.E., Kovesdi I. Adenovirus targeted to heparan-containing receptors increases its gene delivery efficiency to multiple cell types. Nat Biotechnol 1996, 14(11):1570-1573.
93. Stevenson S.C., Rollence M., Marshall-Neff J., McClelland A. Selective targeting of human cells by a chimeric adenovirus vector containing a modified fiber protein. J Virol 1997, 71(6):4782-4790.
94. Krasnykh V.N., Mikheeva G.V., Douglas J.T., Curiel D.T. Generation of recombinant adenovirus vectors with modified fibers for altering viral tropism. J Virol 1996, 70(10):6839-6846.
95. Matsui H., Sakurai F., Kurachi S., Tashiro K., Sugio K., Kawabata K., et al. Development of fiber-substituted adenovirus vectors containing foreign peptides in the adenovirus serotype 35 fiber knob. Gene Ther 2009, 16(8):1050-1057.
96. Li J., Le L., Sibley D.A., Mathis J.M., Curiel D.T. Genetic incorporation of HSV-1 thymidine kinase into the adenovirus protein IX for functional display on the virion. Virology 2005, 338(2):247-258.
97. Liu H., Jin L., Koh S.B., Atanasov I., Schein S., Wu L., et al. Atomic structure of human adenovirus by cryo-EM reveals interactions among protein networks. Science 2010, 329(5995):1038-1043.
98. van Raaij M.J., Mitraki A., Lavigne G., Cusack S. A triple beta-spiral in the adenovirus fibre shaft reveals a new structural motif for a fibrous protein. Nature 1999, 401(6756):935-938.