tetano
Editor, Senior Moderator
Hum Gene Ther. 2014 Mar 18. [Epub ahead of print]
CD46-mediated Transduction of a Species D Adenovirus Vaccine Improves Mucosal Vaccine Efficacy.
Camacho Z1, Turner MA, Barry MA, Weaver EA.
Author information
Abstract
The high levels of pre-existing immunity against Adenovirus type 5 (Ad5) have deemed Ad5 unusable for translation as a human vaccine vector. Low seroprevalent alternative viral vectors may be less impacted by pre-existing immunity, but they may also have significantly different phenotypes than that of Ad5. In this study we compare species D Ads (26, 28 and 48) to the species C Ad5. In vitro transduction studies show striking differences between the species C and D viruses. Most notably, Ad26 transduced human dendritic cells much more effectively than Ad5. In vivo imaging studies showed strikingly different transgene expression profiles. The Ad5 virus was superior to the species D viruses in BALB/c mice when delivered intramuscularly. However, the inverse was true when the viruses were delivered mucosally via the intranasal epithelia. Intramuscular transduction was restored in mice that ubiquitously expressed human CD46, the primary receptor for species D viruses. We analyzed both species C and D Ads for their ability to induce prophylactic immunity against influenza in the CD46 transgenic mouse model. Surprisingly, the species D vaccines again failed to induce greater levels of protective immunity as compared to the species C Ad5 when delivered intramuscularly. However, the species D Ad vaccine vector, Ad48, induced significantly greater protection as compared to Ad5 when delivered mucosally via the intranasal route in CD46 transgenic mice. These data shed light on the complexities between the species and types of Ad. Our findings indicate that more research will be required to identify the mechanisms that play a key role in the induction of protective immunity induced by species D Ad vaccines.
PMID:
24635714
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24635714
CD46-mediated Transduction of a Species D Adenovirus Vaccine Improves Mucosal Vaccine Efficacy.
Camacho Z1, Turner MA, Barry MA, Weaver EA.
Author information
Abstract
The high levels of pre-existing immunity against Adenovirus type 5 (Ad5) have deemed Ad5 unusable for translation as a human vaccine vector. Low seroprevalent alternative viral vectors may be less impacted by pre-existing immunity, but they may also have significantly different phenotypes than that of Ad5. In this study we compare species D Ads (26, 28 and 48) to the species C Ad5. In vitro transduction studies show striking differences between the species C and D viruses. Most notably, Ad26 transduced human dendritic cells much more effectively than Ad5. In vivo imaging studies showed strikingly different transgene expression profiles. The Ad5 virus was superior to the species D viruses in BALB/c mice when delivered intramuscularly. However, the inverse was true when the viruses were delivered mucosally via the intranasal epithelia. Intramuscular transduction was restored in mice that ubiquitously expressed human CD46, the primary receptor for species D viruses. We analyzed both species C and D Ads for their ability to induce prophylactic immunity against influenza in the CD46 transgenic mouse model. Surprisingly, the species D vaccines again failed to induce greater levels of protective immunity as compared to the species C Ad5 when delivered intramuscularly. However, the species D Ad vaccine vector, Ad48, induced significantly greater protection as compared to Ad5 when delivered mucosally via the intranasal route in CD46 transgenic mice. These data shed light on the complexities between the species and types of Ad. Our findings indicate that more research will be required to identify the mechanisms that play a key role in the induction of protective immunity induced by species D Ad vaccines.
PMID:
24635714
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24635714