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Author Notes:

Address correspondence to Rafi Ahmed, rahmed@emory.edu

We thank H. Wu for technical assistance.

Subjects:

Research Funding:

We acknowledge the NIH Tetramer Core Facility (contract HHSN272201300006C) for provision of MHC class II tetramers.

This work was supported by NIH grants AI030048 to R.A. and AI091493 to R.A. and M.J.M.

Keywords:

  • CD4 T cell responses
  • T follicular helper (Tfh)
  • T helper 1 (Th1)
  • adenovirus serotype 5
  • vaccination
  • Adenoviridae
  • Administration, Intravenous
  • Animals
  • Antibodies, Viral
  • Cell Differentiation
  • Female
  • Glycoproteins
  • Injections, Intramuscular
  • Lymphocytic Choriomeningitis
  • Lymphocytic choriomeningitis virus
  • Mice, Inbred C57BL
  • Th1 Cells
  • Vaccination
  • Viral Proteins
  • Viral Vaccines

Adenovirus serotype 5 vaccination results in suboptimal CD4 T helper 1 responses in mice

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Journal Title:

Journal of Virology

Volume:

Volume 91, Number 5

Publisher:

Type of Work:

Article | Final Publisher PDF

Abstract:

Adenovirus serotype 5 (Ad5) is one of the most widely used viral vectors and is known to generate potent T cell responses. While many previous studies have characterized Ad5-induced CD8 T cell responses, there is a relative lack of detailed studies that have analyzed CD4 T cells elicited by Ad5 vaccination. Here, we immunized mice wi th Ad5 vectors encoding lymphocytic choriomeningitis virus (LCMV) glycoprotein (GP) and examined GP-specific CD4 T cell responses elicited by Ad5 vectors and compared them to those induced by an acute LCMV infection. In contrast to LCMV infection, where balanced CD4 T helper 1 (Th1) and T follicular helper (Tfh) responses were induced, Ad5 immunization resulted in a significantly reduced frequency of Th1 cells. CD4 T cells elicited by Ad5 vectors expressed decreased levels of Th1 markers, such as Tim3, SLAM, T-bet, and Ly6C, had smaller amounts of cytotoxic molecules like granzyme B, and produced less interferon gamma than CD4 T cells induced by LCMV infection. This defective CD4 Th1 response appeared to be intrinsic for Ad5 vectors and not a reflection of comparing a nonreplicating vector to a live viral infection, since immunization with a DNA vector expressing LCMV-GP generated efficient CD4 Th1 responses. Analysis at early time points (day 3 or 4) after immunization with Ad5 vectors revealed a defect in the expression of CD25 (interleukin-2 [IL-2] receptor alpha chain) on Ad5-elicited CD4 T cells, and administration of exogenous IL-2 following Ad5 immunization partially restored CD4 Th1 responses. These results suggest that impairment of Th1 commitment after Ad5 immunization could be due to reduced IL-2-mediated signaling.

Copyright information:

© 2017 American Society for Microbiology. All Rights Reserved.

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