Seroprevalence of neutralizing antibodies to human adenovirus type 5 in healthy adults in China

2012 ◽  
Vol 84 (9) ◽  
pp. 1408-1414 ◽  
Author(s):  
Bin Yu ◽  
Yan Zhou ◽  
Hao Wu ◽  
Zhen Wang ◽  
Yang Zhan ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Human Adenovirus ◽  
Adenovirus Type ◽  
Healthy Adults ◽  
Adenovirus Type 5

scholarly journals Replication-Defective Vector Based on a Chimpanzee Adenovirus

2001 ◽  
Vol 75 (23) ◽  
pp. 11603-11613 ◽  
Author(s):  
Steven F. Farina ◽  
Guang-ping Gao ◽  
Z. Q. Xiang ◽  
John J. Rux ◽  
Roger M. Burnett ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Human Adenovirus ◽  
Adenovirus Type ◽  
Open Reading Frames ◽  
Hypervariable Regions ◽  
293 Cells ◽  
Coxsackievirus And Adenovirus Receptor ◽  
Cross Neutralization ◽  
Adenovirus Receptor ◽  
Adenovirus Type 5

ABSTRACT An adenovirus previously isolated from a mesenteric lymph node from a chimpanzee was fully sequenced and found to be similar in overall structure to human adenoviruses. The genome of this virus, called C68, is 36,521 bp in length and is most similar to subgroup E of human adenovirus, with 90% identity in most adenovirus type 4 open reading frames that have been sequenced. Substantial differences in the hexon hypervariable regions were noted between C68 and other known adenoviruses, including adenovirus type 4. Neutralizing antibodies to C68 were highly prevalent in sera from a population of chimpanzees, while sera from humans and rhesus monkeys failed to neutralize C68. Furthermore, infection with C68 was not neutralized from sera of mice immunized with human adenovirus serotypes 2, 4, 5, 7, and 12. A replication-defective version of C68 was created by replacing the E1a and E1b genes with a minigene cassette; this vector was efficiently transcomplemented by the E1 region of human adenovirus type 5. C68 vector transduced a number of human and murine cell lines. This nonhuman adenoviral vector is sufficiently similar to human serotypes to allow growth in 293 cells and transduction of cells expressing the coxsackievirus and adenovirus receptor. As it is dissimilar in regions such as the hexon hypervariable domains, C68 vector avoids significant cross-neutralization by sera directed against human serotypes.

scholarly journals Canine Adenovirus Vectors: an Alternative for Adenovirus-Mediated Gene Transfer

2000 ◽  
Vol 74 (1) ◽  
pp. 505-512 ◽  
Author(s):  
Eric J. Kremer ◽  
Sylvie Boutin ◽  
Miguel Chillon ◽  
Olivier Danos
Keyword(s):  
Gene Transfer ◽  
Neutralizing Antibodies ◽  
Viral Vectors ◽  
Human Adenovirus ◽  
Adenovirus Type ◽  
Serum Samples ◽  
Humoral And Cellular Immunity ◽  
Adenovirus Vectors ◽  
Adenovirus Type 5

ABSTRACT Preclinical studies have shown that gene transfer following readministration of viral vectors is often inefficient due to the presence of neutralizing antibodies. Vectors derived from ubiquitous human adenoviruses may have limited clinical use because preexisting humoral and cellular immunity is found in 90% of the population. Furthermore, risks associated with the use of human adenovirus vectors, such as the need to immunosuppress or tolerize patients to a potentially debilitating virus, are avoidable if efficient nonhuman adenovirus vectors are feasible. Plasmids containing recombinant canine adenovirus (CAV) vectors from which the E1 region had been deleted were generated and transfected into a CAV E1-transcomplementing cell line. Vector stocks, with titers greater than or equal to those obtained with human adenovirus vectors, were free of detectable levels of replication-competent CAV and had a low particle-to-transduction unit ratio. CAV vectors were replication defective in all cell lines tested, transduced human-derived cells at an efficiency similar to that of a comparable human adenovirus type 5 vector, and are amenable to in vivo use. Importantly, 49 of 50 serum samples from healthy individuals did not contain detectable levels of neutralizing CAV antibodies.

scholarly journals In Vitro and In Vivo Evaluation of Human Adenovirus Type 49 as a Vector for Therapeutic Applications

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1483
Author(s):  
Emily A. Bates ◽  
John R. Counsell ◽  
Sophie Alizert ◽  
Alexander T. Baker ◽  
Natalie Suff ◽  
...  
Keyword(s):  
Viral Vector ◽  
Ex Vivo ◽  
Human Adenovirus ◽  
Adenovirus Type ◽  
Cell Types ◽  
In Vivo Evaluation ◽  
In Vivo Biodistribution ◽  
Adenovirus Type 5

The human adenovirus phylogenetic tree is split across seven species (A–G). Species D adenoviruses offer potential advantages for gene therapy applications, with low rates of pre-existing immunity detected across screened populations. However, many aspects of the basic virology of species D—such as their cellular tropism, receptor usage, and in vivo biodistribution profile—remain unknown. Here, we have characterized human adenovirus type 49 (HAdV-D49)—a relatively understudied species D member. We report that HAdV-D49 does not appear to use a single pathway to gain cell entry, but appears able to interact with various surface molecules for entry. As such, HAdV-D49 can transduce a broad range of cell types in vitro, with variable engagement of blood coagulation FX. Interestingly, when comparing in vivo biodistribution to adenovirus type 5, HAdV-D49 vectors show reduced liver targeting, whilst maintaining transduction of lung and spleen. Overall, this presents HAdV-D49 as a robust viral vector platform for ex vivo manipulation of human cells, and for in vivo applications where the therapeutic goal is to target the lung or gain access to immune cells in the spleen, whilst avoiding liver interactions, such as intravascular vaccine applications.

The endosomal epsilon-coatomer protein is involved in human adenovirus type 5 internalisation

2002 ◽  
Vol 50 (4) ◽  
pp. 481-489 ◽  
Author(s):  
Cs. Jeney ◽  
Boglárka Banizs ◽  
Orsolya Dobay ◽  
Keyword(s):  
Chinese Hamster ◽  
Human Adenovirus ◽  
Adenovirus Type ◽  
Inhibitory Effect ◽  
Bafilomycin A1 ◽  
Cho Cell ◽  
Coxsackie Adenovirus Receptor ◽  
Downstream Effector ◽  
Adenovirus Receptor ◽  
Adenovirus Type 5

The effects of bafilomycin A1 and of the reduced level of endosomal epsilon-COP (coatomer protein) on the infectivity of human adenovirus type 5 were investigated in Coxsackie adenovirus receptor- (CAR-) transfected Chinese hamster ovary (CHO) cells. The endosomal proton pump inhibitor bafilomycin A1 was able to cause only partial inhibition. Using ldlF cells (an epsilon-COP thermosensitive mutant CHO cell line) the reduction of epsilon-COP level also had partial inhibitory effect. Based on these results and comparing them to existing models of the adenovirus entry, we propose a refined model in which there are two pathways of adenoviral entry: the first one involves the epsilon-COP as the downstream effector of the acidification and can be blocked by bafilomycin A1 and the second one is a pH-independent pathway.

scholarly journals Hexon Hypervariable Region-Modified Adenovirus Type 5 (Ad5) Vectors Display Reduced Hepatotoxicity but Induce T Lymphocyte Phenotypes Similar to Ad5 Vectors

2014 ◽  
Vol 21 (8) ◽  
pp. 1137-1144 ◽  
Author(s):  
Jeffrey E. Teigler ◽  
Pablo Penaloza-MacMaster ◽  
Rebecca Obeng ◽  
Nicholas M. Provine ◽  
Rafael A. Larocca ◽  
...  
Keyword(s):  
Immune Responses ◽  
Neutralizing Antibodies ◽  
Hypervariable Region ◽  
Adenovirus Type ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Cytokines And Chemokines ◽  
Programmed Death 1 ◽  
Lymphocyte Phenotypes ◽  
Adenovirus Type 5

ABSTRACTHexon modification of adenovirus type 5 (Ad5) vectors with the hypervariable regions (HVRs) of Ad48 has been shown to allow Ad5HVR48 vectors to circumvent the majority of the preexisting Ad5-neutralizing antibodies. However, it remains unclear whether modifying hexon HVRs impacts innate or adaptive immune responses elicited by this vector. In this study, we investigated the influence of the HVR substitution of Ad5 on innate and adaptive immune responses following vaccination. Ad5HVR48 displayed an intermediate level of innate immune cytokines and chemokines relative to those of Ad5 and Ad48, consistent with its chimeric nature. Hepatotoxicity was observed after Ad5 immunization but not after Ad5HVR48 or Ad48 immunization. However, the CD8+T-cell responses elicited by Ad5HVR48 vectors displayed a partially exhausted phenotype, as evidenced by the sustained expression of programmed death 1 (PD-1), decreased effector-to-central memory conversion, and reduced memory recall responses, similar to those elicited by Ad5 vectors and in contrast to those induced by Ad48 vectors. Taken together, these results indicate that although Ad5HVR48 largely bypasses preexisting Ad5 neutralizing antibodies and shows reduced hepatotoxicity compared to that of Ad5, it induces adaptive immune phenotypes that are functionally exhausted similar to those elicited by Ad5.

scholarly journals Chimpanzee adenovirus CV-68 adapted as a gene delivery vector interacts with the coxsackievirus and adenovirus receptor

2002 ◽  
Vol 83 (1) ◽  
pp. 151-155 ◽  
Author(s):  
Christopher J. Cohen ◽  
Zhi Quan Xiang ◽  
Guang-Ping Gao ◽  
Hildegund C. J. Ertl ◽  
James M. Wilson ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Cho Cells ◽  
Human Adenovirus ◽  
Adenovirus Type ◽  
Soluble Form ◽  
Delivery Vector ◽  
Coxsackievirus And Adenovirus Receptor ◽  
Adenovirus Receptor ◽  
Adenovirus Type 5 ◽  
Dependent Mechanism

A replication-defective form of chimpanzee adenovirus type 68 (C68) has been developed to circumvent problems posed by widespread preexisting immunity to common human adenovirus vectors. To investigate the determinants of C68 tropism, its interaction with the coxsackievirus and adenovirus receptor (CAR) was studied. Although CHO cells were resistant to transduction by C68 as well as by adenovirus type 5 (Ad5), CHO cells expressing either human or murine CAR were transduced readily. C68 transduction, like Ad5 transduction, was blocked when cells were exposed to anti-CAR antibody or when virus was exposed to a soluble form of the CAR extracellular domain. These results indicate that gene delivery by C68 occurs by a CAR-dependent mechanism.

scholarly journals Bovine herpesvirus 1 glycoprotein D expression in bovine upper respiratory tract mediated by a human adenovirus type 5

2004 ◽  
Vol 35 (6) ◽  
pp. 715-721 ◽  
Author(s):  
Sacha Gogev ◽  
Jean-Pierre Georgin ◽  
Fr�d�ric Schynts ◽  
Alain Vanderplasschen ◽  
Etienne Thiry
Keyword(s):  
Respiratory Tract ◽  
Bovine Herpesvirus ◽  
Human Adenovirus ◽  
Adenovirus Type ◽  
Upper Respiratory Tract ◽  
Glycoprotein D ◽  
Bovine Herpesvirus 1 ◽  
Upper Respiratory ◽  
Herpesvirus 1 ◽  
Adenovirus Type 5

scholarly journals Comparative Sequence Analysis of the Largest E1A Proteins of Human and Simian Adenoviruses

2002 ◽  
Vol 76 (16) ◽  
pp. 7968-7975 ◽  
Author(s):  
Nikita Avvakumov ◽  
Russ Wheeler ◽  
Jean Claude D'Halluin ◽  
Joe S. Mymryk
Keyword(s):  
Gene Expression ◽  
Human Adenovirus ◽  
Detailed Comparison ◽  
Adenovirus Type ◽  
Comparative Sequence Analysis ◽  
Regulatory Proteins ◽  
Carboxyl Terminus ◽  
Adenovirus E1a ◽  
Simian Adenovirus ◽  
Adenovirus Type 5

ABSTRACT The early region 1A (E1A) gene is the first gene expressed after infection with adenovirus and has been most extensively characterized in human adenovirus type 5 (hAd5). The E1A proteins interact with numerous cellular regulatory proteins, influencing a variety of transcriptional and cell cycle events. For this reason, these multifunctional proteins have been useful as tools for dissecting pathways regulating cell growth and gene expression. Despite the large number of studies using hAd5 E1A, relatively little is known about the function of the E1A proteins of other adenoviruses. In 1985, a comparison of E1A sequences from three human and one simian adenovirus identified three regions with higher overall levels of sequence conservation designated conserved regions (CR) 1, 2, and 3. As expected, these regions are critical for a variety of E1A functions. Since that time, the sequences of several other human and simian adenovirus E1A proteins have been determined. Using these, and two additional sequences that we determined, we report here a detailed comparison of the sequences of 15 E1A proteins representing each of the six hAd subgroups and several simian adenoviruses. These analyses refine the positioning of CR1, 2, and 3; define a fourth CR located near the carboxyl terminus of E1A; and suggest several new functions for E1A.

Mapping of cellular protein-binding sites on the products of early-region 1A of human adenovirus type 5

1988 ◽  
Vol 8 (9) ◽  
pp. 3955-3959 ◽  
Author(s):  
C Egan ◽  
T N Jelsma ◽  
J A Howe ◽  
S T Bayley ◽  
B Ferguson ◽  
...  
Keyword(s):  
Biological Activity ◽  
Binding Sites ◽  
Human Adenovirus ◽  
Adenovirus Type ◽  
Cellular Protein ◽  
Cellular Proteins ◽  
Deletion Mutants ◽  
Protein Binding Sites ◽  
Amino Terminal ◽  
Adenovirus Type 5

The binding sites for the 300-, 107-, and 105-kilodalton cellular proteins which associate with human adenovirus type 5 E1A products were studied with E1A deletion mutants. All appeared to bind to the amino-terminal half of E1A products in regions necessary for oncogenic transformation. These results suggest that these cellular species may be important for the biological activity of E1A products.

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