The prevalence of antibodies to adenovirus serotype 5 in an adult Indian population and implications for adenovirus vector vaccines

2010 ◽  
Vol 82 (3) ◽  
pp. 407-414 ◽  
Author(s):  
Rajendra Pilankatta ◽  
Tanu Chawla ◽  
Navin Khanna ◽  
Sathyamangalam Swaminathan
Keyword(s):  
Indian Population ◽  
Adenovirus Vector ◽  
Adenovirus Serotype ◽  
Serotype 5

scholarly journals Construction and Characterization of Adenovirus Serotype 5 Packaged by Serotype 3 Hexon

2002 ◽  
Vol 76 (24) ◽  
pp. 12775-12782 ◽  
Author(s):  
Hongju Wu ◽  
Igor Dmitriev ◽  
Elena Kashentseva ◽  
Toshiro Seki ◽  
Minghui Wang ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Hela Cells ◽  
Neutralizing Antibodies ◽  
Adenovirus Vector ◽  
Repeated Administration ◽  
Hexon Gene ◽  
Adenovirus Serotype ◽  
Serotype 5 ◽  
Neutralization Response

ABSTRACT Adenovirus serotype 5 (Ad5) has great potential for gene therapy applications. A major limitation, however, is the host immune response against Ad5 infection that often prevents the readministration of Ad5 vectors. In this regard, the most abundant capsid protein, hexon, has been implicated as the major target for neutralizing antibodies. In this study, we sought to escape the host neutralization response against Ad5 via hexon replacement. We constructed a chimeric adenovirus vector, Ad5/H3, by replacing the Ad5 hexon gene with the hexon gene of Ad3. The chimeric viruses were successfully rescued in 293 cells. Compared to that for the control Ad5/H5, the growth rate of Ad5/H3 was significantly slower and the final yield was about 1 log order less. These data indicate that the Ad3 hexon can encapsidate the Ad5 genome, but with less efficiency than the Ad5 hexon. The gene transfer efficacy of Ad5/H3 in HeLa cells was also lower than that of Ad5/H5. Furthermore, we tested the host neutralization responses against the two viruses by using C57BL/6 mice. The neutralizing antibodies against Ad5/H3 and Ad5/H5 generated by the immunized mice did not cross-neutralize each other in the context of in vitro infection of HeLa cells. Preimmunization of C57BL/6 mice with one of the two types of viruses also did not prevent subsequent infection of the other type. These data suggest that replacing the Ad5 hexon with the Ad3 hexon can circumvent the host neutralization response to Ad5. This strategy may therefore be used to achieve the repeated administration of Ad5 in gene therapy applications.

scholarly journals Comparison of Liver Detargeting Strategies for Systemic Therapy with Oncolytic Adenovirus Serotype 5

Biomedicines ◽  
2017 ◽  
Vol 5 (4) ◽  
pp. 46 ◽  
Author(s):  
Tien Nguyen ◽  
Mary Barry ◽  
Mallory Turner ◽  
Catherine Crosby ◽  
Miguel Trujillo ◽  
...  
Keyword(s):  
Systemic Therapy ◽  
Oncolytic Adenovirus ◽  
Adenovirus Serotype ◽  
Serotype 5

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 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.

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