Immunogenicity of recombinant adenovirus serotype 35 vaccine in the presence of pre-existing anti-Ad5 immunity.
The high prevalence of pre-existing immunity to adenovirus serotype 5 (Ad5) in human populations may substantially limit the immunogenicity and clinical utility of recombinant Ad5 vector-based vaccines for HIV-1 and other pathogens. A potential solution to this problem is to use vaccine vectors derived from adenovirus (Ad) serotypes that are rare in humans, such as Ad35. However, cross-reactive immune responses between heterologous Ad serotypes have been described and could prove a major limitation of this strategy. In particular, the extent of immunologic cross-reactivity between Ad5 and Ad35 has not previously been determined. In this study we investigate the impact of pre-existing anti-Ad5 immunity on the immunogenicity of candidate rAd5 and rAd35 vaccines expressing SIV Gag in mice. Anti-Ad5 immunity at levels typically found in humans dramatically blunted the immunogenicity of rAd5-Gag. In contrast, even high levels of anti-Ad5 immunity did not substantially suppress Gag-specific cellular immune responses elicited by rAd35-Gag. Low levels of cross-reactive Ad5/Ad35-specific CD4(+) T lymphocyte responses were observed, but were insufficient to suppress vaccine immunogenicity. These data demonstrate the potential utility of Ad35 as a candidate vaccine vector that is minimally suppressed by anti-Ad5 immunity. Moreover, these studies suggest that using Ad vectors derived from immunologically distinct serotypes may be an effective and general strategy to overcome the suppressive effects of pre-existing anti-Ad immunity.
Barouch
Dan H
DH
Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. dbarouch@bidmc.harvard.edu
Pau
Maria G
MG
Custers
Jerome H H V
JH
Koudstaal
Wouter
W
Kostense
Stefan
S
Havenga
Menzo J E
MJ
Truitt
Diana M
DM
Sumida
Shawn M
SM
Kishko
Michael G
MG
Arthur
Janelle C
JC
Korioth-Schmitz
Birgit
B
Newberg
Michael H
MH
Gorgone
Darci A
DA
Lifton
Michelle A
MA
Panicali
Dennis L
DL
Nabel
Gary J
GJ
Letvin
Norman L
NL
Goudsmit
Jaap
J
D000256:Adenoviridae / Q000145:classification / Q000235:genetics* / Q000276:immunology*; D000257:Adenoviridae Infections / Q000276:immunology* / Q000517:prevention & control*; D000595:Amino Acid Sequence; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D004306:Dose-Response Relationship, Immunologic; D018604:Epitope Mapping / Q000379:methods; D018984:Epitopes, T-Lymphocyte / Q000097:blood; D015683:Gene Products, gag / Q000008:administration & dosage / Q000097:blood / Q000276:immunology; D005822:Genetic Vectors; D007110:Immunity, Active; D007115:Immunization Schedule; D007117:Immunization, Secondary; D007273:Injections, Intramuscular; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D012703:Serotyping; D015302:Simian Immunodeficiency Virus / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage / Q000235:genetics* / Q000276:immunology*
D018984:Epitopes, T-Lymphocyte; D015683:Gene Products, gag; D010446:Peptide Fragments; D014614:Vaccines, Synthetic; D014765:Viral Vaccines