scholarly journals A Phase 1/2 Study of a Multiclade HIV‐1 DNA Plasmid Prime and Recombinant Adenovirus Serotype 5 Boost Vaccine in HIV‐Uninfected East Africans (RV 172)

2010 ◽  
Vol 201 (4) ◽  
pp. 600-607 ◽  
Author(s):  
Hannah Kibuuka ◽  
Robert Kimutai ◽  
Leonard Maboko ◽  
Fred Sawe ◽  
Mirjam S. Schunk ◽  
...  
Keyword(s):  
Recombinant Adenovirus ◽  
Phase 1 ◽  
Adenovirus Serotype ◽  
Boost Vaccine ◽  
Serotype 5 ◽  
Dna Plasmid ◽  
Hiv 1

scholarly journals First-in-human phase 1 trial of the safety and immunogenicity of a recombinant adenovirus serotype 5 HVR48 (rAd5HVR48) HIV-1 vaccine

Retrovirology ◽  
2012 ◽  
Vol 9 (S2) ◽  
Author(s):  
SR Walsh ◽  
MS Seaman ◽  
JA Johnson ◽  
RP Tucker ◽  
KH Krause ◽  
...  
Keyword(s):  
Recombinant Adenovirus ◽  
Phase 1 ◽  
Adenovirus Serotype ◽  
Phase 1 Trial ◽  
Serotype 5 ◽  
Hiv 1

scholarly journals Immunogenicity of Heterologous Prime-Boost Regimens Involving Recombinant Adenovirus Serotype 11 (Ad11) and Ad35 Vaccine Vectors in the Presence of Anti-Ad5 Immunity

2005 ◽  
Vol 79 (15) ◽  
pp. 9694-9701 ◽  
Author(s):  
Angelique A. C. Lemckert ◽  
Shawn M. Sumida ◽  
Lennart Holterman ◽  
Ronald Vogels ◽  
Diana M. Truitt ◽  
...  
Keyword(s):  
Immune Responses ◽  
Recombinant Adenovirus ◽  
Human Populations ◽  
Vaccine Vectors ◽  
Adenovirus Serotype ◽  
Immunodeficiency Virus ◽  
High Prevalence ◽  
Boost Vaccine ◽  
Serotype 5 ◽  
Cellular Immune

ABSTRACT The high prevalence of preexisting immunity to adenovirus serotype 5 (Ad5) in human populations will likely limit the immunogenicity and clinical utility of recombinant Ad5 (rAd5) vector-based vaccines for human immunodeficiency virus type 1 and other pathogens. A potential solution to this problem is to utilize rAd vaccine vectors derived from rare Ad serotypes such as Ad35 and Ad11. We have previously reported that rAd35 vectors were immunogenic in the presence of anti-Ad5 immunity, but the immunogenicity of heterologous rAd prime-boost regimens and the extent that cross-reactive anti-vector immunity may limit this approach have not been fully explored. Here we assess the immunogenicity of heterologous vaccine regimens involving rAd5, rAd35, and novel rAd11 vectors expressing simian immunodeficiency virus Gag in mice both with and without anti-Ad5 immunity. Heterologous rAd prime-boost regimens proved significantly more immunogenic than homologous regimens, as expected. Importantly, all regimens that included rAd5 were markedly suppressed by anti-Ad5 immunity. In contrast, rAd35-rAd11 and rAd11-rAd35 regimens elicited high-frequency immune responses both in the presence and in the absence of anti-Ad5 immunity, although we also detected clear cross-reactive Ad35/Ad11-specific humoral and cellular immune responses. Nevertheless, these data suggest the potential utility of heterologous rAd prime-boost vaccine regimens using vectors derived from rare human Ad serotypes.

scholarly journals Mucosal Trafficking of Vector-Specific CD4+ T Lymphocytes following Vaccination of Rhesus Monkeys with Adenovirus Serotype 5

2010 ◽  
Vol 84 (19) ◽  
pp. 9810-9816 ◽  
Author(s):  
Katherine Masek-Hammerman ◽  
Hualin Li ◽  
Jinyan Liu ◽  
Peter Abbink ◽  
Annalena La Porte ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Rhesus Monkeys ◽  
Vaccine Development ◽  
Recombinant Adenovirus ◽  
Target Cells ◽  
Adenovirus Serotype ◽  
Increased Risk ◽  
Serotype 5 ◽  
Step Study ◽  
Hiv 1

ABSTRACT Post hoc analysis of the phase 2b Step study evaluating a recombinant adenovirus serotype 5 (rAd5)-based HIV-1 vaccine candidate suggested a potential increased risk of HIV-1 acquisition in subjects who were baseline Ad5 seropositive and uncircumcised. These concerns had a profound impact on the HIV-1 vaccine development field, although the mechanism underlying this observation remains unknown. It has been hypothesized that rAd5 vaccination of baseline Ad5-seropositive individuals may have resulted in anamnestic, vector-specific CD4+ T lymphocytes that could have trafficked to mucosal sites and served as increased targets for HIV-1 infection. Here we show that Ad5-specific CD4+ T lymphocyte responses at mucosal sites following rAd5-Gag/Pol/Nef vaccination were comparable in rhesus monkeys with and without baseline Ad5 immunity. Moreover, the total cellular inflammatory infiltrates and the CD3+, CD4+, HLA-DR+, Ki67+, and langerin+ cellular subpopulations in colorectal and foreskin mucosa were similar in both groups. Thus, no greater trafficking of Ad5-specific CD4+ T lymphocytes to mucosal target sites was observed following rAd5 vaccination of rhesus monkeys with baseline Ad5 immunity. These findings from this nonhuman primate model provide evidence against the hypothesis that recruitment of vector-specific target cells to mucosal sites led to increased HIV-1 acquisition in Ad5-seropositive, uncircumcised vaccinees in the Step study.

scholarly journals Adenovirus-Platelet Interaction in Blood Causes Virus Sequestration to the Reticuloendothelial System of the Liver

2007 ◽  
Vol 81 (9) ◽  
pp. 4866-4871 ◽  
Author(s):  
Daniel Stone ◽  
Ying Liu ◽  
Dmitry Shayakhmetov ◽  
Zong-Yi Li ◽  
Shaoheng Ni ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Target Cell ◽  
Recombinant Adenovirus ◽  
Reticuloendothelial System ◽  
Adenovirus Serotype ◽  
Safety And Efficacy ◽  
Liver Sinusoids ◽  
Serotype 5 ◽  
Platelet Aggregates ◽  
Platelet Depletion

ABSTRACT Intravenous (i.v.) delivery of recombinant adenovirus serotype 5 (Ad5) vectors for gene therapy is hindered by safety and efficacy problems. We have discovered a new pathway involved in unspecific Ad5 sequestration and degradation. After i.v. administration, Ad5 rapidly binds to circulating platelets, which causes their activation/aggregation and subsequent entrapment in liver sinusoids. Virus-platelet aggregates are taken up by Kupffer cells and degraded. Ad sequestration in organs can be reduced by platelet depletion prior to vector injection. Identification of this new sequestration mechanism and construction of vectors that avoid it could improve levels of target cell transduction at lower vector doses.

scholarly journals Immunogenicity of Recombinant Fiber-Chimeric Adenovirus Serotype 35 Vector-Based Vaccines in Mice and Rhesus Monkeys

2005 ◽  
Vol 79 (22) ◽  
pp. 14161-14168 ◽  
Author(s):  
Anjali Nanda ◽  
Diana M. Lynch ◽  
Jaap Goudsmit ◽  
Angelique A. C. Lemckert ◽  
Bonnie A. Ewald ◽  
...  
Keyword(s):  
Rhesus Monkeys ◽  
In Vivo Studies ◽  
Preclinical Studies ◽  
Adenovirus Serotype ◽  
Immunodeficiency Virus ◽  
Serotype 5 ◽  
Fiber Proteins ◽  
Hiv 1

ABSTRACT Preexisting immunity to adenovirus serotype 5 (Ad5) has been shown to suppress the immunogenicity of recombinant Ad5 (rAd5) vector-based vaccines for human immunodeficiency virus type 1 (HIV-1) in both preclinical studies and clinical trials. A potential solution to this problem is to utilize rAd vectors derived from rare Ad serotypes, such as Ad35. However, rAd35 vectors have appeared less immunogenic than rAd5 vectors in preclinical studies to date. In this study, we explore the hypothesis that the differences in immunogenicity between rAd5 and rAd35 vectors may be due in part to differences between the fiber proteins of these viruses. We constructed capsid chimeric rAd35 vectors containing the Ad5 fiber knob (rAd35k5) and compared the immunogenicities of rAd5, rAd35k5, and rAd35 vectors expressing simian immunodeficiency virus Gag and HIV-1 Env in mice and rhesus monkeys. In vitro studies demonstrated that rAd35k5 vectors utilized the Ad5 receptor CAR rather than the Ad35 receptor CD46. In vivo studies showed that rAd35k5 vectors were more immunogenic than rAd35 vectors in both mice and rhesus monkeys. These data suggest that the Ad5 fiber knob contributes substantially to the immunogenicity of rAd vectors. Moreover, these studies demonstrate that capsid chimeric rAd vectors can be constructed to combine beneficial immunologic and serologic properties of different Ad serotypes.

scholarly journals Phase 1 Safety and Immunogenicity Evaluation of a Multiclade HIV‐1 Candidate Vaccine Delivered by a Replication‐Defective Recombinant Adenovirus Vector

2006 ◽  
Vol 194 (12) ◽  
pp. 1638-1649 ◽  
Author(s):  
Andrew T. Catanzaro ◽  
Richard A. Koup ◽  
Mario Roederer ◽  
Robert T. Bailer ◽  
Mary E. Enama ◽  
...  
Keyword(s):  
Recombinant Adenovirus ◽  
Phase 1 ◽  
Adenovirus Vector ◽  
Candidate Vaccine ◽  
Recombinant Adenovirus Vector ◽  
Hiv 1
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