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Adenovirus serotypes differ in their susceptibility to neutralization by mouse serum: role of coagulation factor X

Friday, November 08, 2013 — Poster Session IV

2:00 p.m. – 4:00 p.m.

FAES Academic Center (Upper-Level Terrace)

FDA/CBER

VIROL-8

Authors

  • J. Tian
  • Z. Xu
  • Q. Qiu
  • A. P. Byrnes

Abstract

Ad5 vectors have the ability to bind FX, and we have recently shown that FX protects Ad5 from neutralization by complement. When Ad5 is prevented from binding FX, naive mouse serum can neutralize Ad5 through natural IgM and the classical complement pathway. Beyond Ad5, additional Ad serotypes are increasingly being used as gene therapy vectors and vaccines. Here, we have examined whether other Ad serotypes are neutralized by naive mouse serum, and whether FX plays a role in protecting non-Ad5 viruses from neutralization. Various wild-type human adenoviruses were incubated with freshly-collected serum from naive C57BL/6 mice and infected on 293 cells. In some cases FX was blocked using X-bp. As expected, Ad5 retained full infectivity in naive mouse serum, and became neutralized when FX in the serum was blocked using X-bp. With non-Ad5 serotypes, interestingly, we found that mouse serum neutralized some Ad serotypes in spite of the presence of FX. On the other hand, a number of other Ad serotypes remained infectious in serum even when FX was blocked. We conclude that Ad serotypes differ in their susceptibility to neutralization by mouse serum, as well as differing in whether they rely on FX for protection from neutralization.

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