title: Induction of both cellular and humoral immunity following a rational prime-boost immunization regimen that incorporates recombinant ovine atadenovirus and fowlpox virus.
abstract: Recombinant fowlpox viruses (rFPV) and ovine atadenoviruses (rOAdV) are being developed as safe, nonpathogenic, prophylactic and therapeutic vaccine vectors. There is scope, however, to improve the limited immune responses elicited by each of these vaccine vectors. Using previously determined and optimized routes of administration and viral doses, we characterized the primary adaptive immune responses elicited by recombinant variants of each virus. We demonstrate the contrasting nature of the response elicited by each recombinant virus. Whereas rFPV generates predominately cell-mediated immunity to our nominal target antigen, ovalbumin (OVA), rOAdV drives strong humoral responses. By defining the time taken to achieve maximal cytotoxic T cell responses and by studying the different patterns and kinetics of major histocompatibility complex class I-restricted OVA antigen expression postimmunization, we proposed a heterologous prime-boost regimen of immunization with rOAdV followed by rFPV. The subsequent experimental results showed that this approach produced robust cell-mediated and humoral immune responses against OVA that, importantly, were accompanied by weak anti-viral vector antibody responses. These results, therefore, represent a novel and potentially clinically applicable way to achieve broadly based and effective immunity to the antigens encoded by vectored vaccines.
authors.affiliation: Experimental Therapeutics Laboratory, Hanson Institute, Adelaide, SA 5000, Australia.
authors.forename: Cara K
authors.initials: CK
authors.lastname: Fraser
authors.forename: Kerrilyn R
authors.initials: KR
authors.lastname: Diener
authors.forename: Erin L
authors.initials: EL
authors.lastname: Lousberg
authors.forename: Gerald W
authors.initials: GW
authors.lastname: Both
authors.forename: Larry
authors.initials: L
authors.lastname: Ward
authors.forename: Michael P
authors.initials: MP
authors.lastname: Brown
authors.forename: John D
authors.initials: JD
authors.lastname: Hayball
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood* / Q000276:immunology; D046808:Atadenovirus / Q000235:genetics*; D004337:Drug Carriers; D005587:Fowlpox virus / Q000235:genetics*; D005822:Genetic Vectors; D007117:Immunization, Secondary / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014611:Vaccination / Q000379:methods*; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D004337:Drug Carriers; D014614:Vaccines, Synthetic; D014765:Viral Vaccines; D010047:Ovalbumin
references.citation: J Virol. 2010 Jul;84(13):6549-63
references.pmid: 20410285
references.citation: Gene Ther. 1996 May;3(5):412-20
references.pmid: 9156802
references.citation: J Immunol. 2002 Oct 15;169(8):4222-9
references.pmid: 12370352
references.citation: Clin Cancer Res. 2008 May 15;14(10):3060-9
references.pmid: 18483372
references.citation: J Virol. 1999 Aug;73(8):6930-6
references.pmid: 10400791
references.citation: J Immunol. 2001 May 1;166(9):5327-30
references.pmid: 11313367
references.citation: Cancer Immunol Immunother. 2010 May;59(5):663-74
references.pmid: 19890632
references.citation: Virology. 1997 Dec 8;239(1):226-37
references.pmid: 9426462
references.citation: J Virol. 2002 Nov;76(21):10882-93
references.pmid: 12368331
references.citation: Vaccine. 2004 Jul 29;22(21-22):2717-21
references.pmid: 15246602
references.citation: Methods Mol Med. 2007;130:69-90
references.pmid: 17401165
references.citation: Appl Microbiol Biotechnol. 2007 Oct;76(5):1131-6
references.pmid: 17581748
references.citation: Clin Cancer Res. 2003 Aug 1;9(8):2973-80
references.pmid: 12912944
references.citation: J Virol. 2005 May;79(10):6516-22
references.pmid: 15858035
references.citation: Clin Vaccine Immunol. 2008 Apr;15(4):691-6
references.pmid: 18272665
references.citation: J Virol. 2003 Nov;77(22):11941-51
references.pmid: 14581531
references.citation: J Virol. 2010 Jun;84(12):5898-908
references.pmid: 20375158
references.citation: Proc Natl Acad Sci U S A. 1996 Oct 15;93(21):11349-53
references.pmid: 8876138
references.citation: Gene Ther. 1996 Feb;3(2):137-44
references.pmid: 8867861
references.citation: Science. 2007 Jan 5;315(5808):107-11
references.pmid: 17204652
references.citation: Hum Vaccin. 2007 Nov-Dec;3(6):260-7
references.pmid: 18340117
references.citation: Immunity. 1994 Aug;1(5):433-42
references.pmid: 7533647
references.citation: J Exp Med. 2002 Sep 16;196(6):817-27
references.pmid: 12235214
references.citation: Expert Rev Vaccines. 2006 Aug;5(4):565-77
references.pmid: 16989636
references.citation: Vet Microbiol. 1994 Aug 1;41(3):281-91
references.pmid: 7975153
references.citation: J Exp Med. 2000 Dec 18;192(12):1685-96
references.pmid: 11120766
references.citation: Vaccine. 1988 Dec;6(6):466-8
references.pmid: 2854335
references.citation: Vaccine. 2008 Jul 4;26(29-30):3566-73
references.pmid: 18541346
references.citation: Proc Natl Acad Sci U S A. 1995 Feb 28;92(5):1401-5
references.pmid: 7877990
references.citation: Vaccine. 2009 Dec 11;28(2):474-83
references.pmid: 19853074
references.citation: N Engl J Med. 2009 Dec 3;361(23):2209-20
references.pmid: 19843557
references.citation: Immunol Cell Biol. 2000 Apr;78(2):110-7
references.pmid: 10762410
references.citation: Proc Natl Acad Sci U S A. 2006 Jul 11;103(28):10729-34
references.pmid: 16807294
references.citation: Immunity. 2007 Jun;26(6):827-41
references.pmid: 17555991
references.citation: Lancet. 2008 Nov 29;372(9653):1881-1893
references.pmid: 19012954
references.citation: Biotechniques. 2004 Jul;37(1):104-6, 108-11
references.pmid: 15283207
references.citation: J Exp Med. 2008 Jan 21;205(1):7-12
references.pmid: 18195078
references.citation: J Exp Med. 2002 Oct 21;196(8):1079-90
references.pmid: 12391019
references.citation: J Immunother. 2009 Oct;32(8):870-4
references.pmid: 19752747
references.citation: Curr Opin Biotechnol. 2007 Dec;18(6):546-56
references.pmid: 18063357
references.citation: Arch Virol. 1998;143(4):829-37
references.pmid: 9638153
references.citation: Science. 2003 Sep 26;301(5641):1925-8
references.pmid: 14512632
references.citation: Vaccine. 2008 Dec 9;26(52):6883-93
references.pmid: 18940219
references.citation: Clin Cancer Res. 2008 Aug 15;14(16):5284-91
references.pmid: 18698048
references.citation: Blood. 2007 Sep 15;110(6):1916-23
references.pmid: 17510320
references.citation: Exp Hematol. 2008 Jan;36(1):51-60
references.pmid: 17949888
references.citation: AIDS. 2010 Aug 24;24(13):1983-90
references.pmid: 20634666
references.citation: Curr Opin Mol Ther. 2009 Aug;11(4):421-32
references.pmid: 19649987
references.citation: J Exp Med. 2002 May 20;195(10):1289-302
references.pmid: 12021309
references.citation: J Immunol Methods. 1994 May 2;171(1):131-7
references.pmid: 8176234
references.citation: J Virol. 2004 Oct;78(20):11434-8
references.pmid: 15452269
references.citation: Immunol Rev. 2010 Mar;234(1):142-62
references.pmid: 20193017