Replication-attenuated Human Adenoviral Type 4 vectors elicit capsid dependent enhanced innate immune responses that are partially dependent upon interactions with the complement system.

Abstract:

:Human Adenovirus Type 4 (HAdV-4) is responsible for epidemic outbreaks of Acute Respiratory Disease (especially in military recruits), and is known to cause significant morbidity with several reported cases of mortality. However, we do not understand why this serotype causes such high morbidity, and have little insight into the immunobiology of HAdV-4 infections. We have now developed a replication attenuated HAdV-4 vector system, and through it, demonstrate that HAdV-4 virions have enhanced infectivity of certain cell types and reveal aspects of the serotype-specific heightened innate immunogenicity of infectious HAdV-4 capsids both in vitro and in vivo. We further found that elements of this serotype-specific immunogenicity were dependent upon interactions with the complement system. These findings provide insights into the mechanisms possibly underlying the known morbidity accompanying wild-type HAdV-4 infections as well as highlight important considerations when considering development of alternative serotype vectors.

journal_name

Virology

journal_title

Virology

authors

Hartman ZC,Appledorn DM,Serra D,Glass O,Mendelson TB,Clay TM,Amalfitano A

doi

10.1016/j.virol.2008.01.017

subject

Has Abstract

pub_date

2008-05-10 00:00:00

pages

453-67

issue

2

eissn

0042-6822

issn

1096-0341

pii

S0042-6822(08)00010-X

journal_volume

374

pub_type

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