Incorporation of CD40 ligand into the envelope of pseudotyped single-cycle simian immunodeficiency viruses enhances immunogenicity

Fan Ching Lin, Yue Peng, Leslie A. Jones, Paulo H. Verardi, Tilahun Yilma

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

A vaccine for the prevention of human immunodeficiency virus (HIV) infection is desperately needed to control the AIDS pandemic. To address this problem, we developed vesicular stomatitis virus glycoprotein-pseudotyped replication-defective simian immunodeficiency viruses (dSIVs) as an AIDS vaccine strategy. The dSIVs retain characteristics of a live attenuated virus without the drawbacks of potential virulence caused by replicating virus. To improve vaccine immunogenicity, we incorporated CD40 ligand (CD40L) into the dSIV envelope. CD40L is one of the most potent stimuli for dendritic cell (DC) maturation and activation. Binding of CD40L to its receptor upregulates expression of major histocompatibility complex class I, class II, and costimulatory molecules on DCs and increases production of proinflammatory cytokines and chemokines, especially interleukin 12 (IL-12). This cytokine polarizes CD4+ T cells to Th1-type immune responses. DC activation and mixed lymphocyte reaction (MLR) studies were performed to evaluate the immunogenicity of CD40L-dSIV in vitro. Expression levels of CD80, CD86, HLA-DR, and CD54 on DCs transduced with the dSIV incorporating CD40L (CD40L-dSIV) were significantly higher than on those transduced with dSIV. Moreover, CD40L-dSIV-transduced DCs expressed up to 10-fold more IL-12 than dSIV-transduced DCs. CD40L-dSIV-transduced DCs enhanced proliferation and gamma interferon secretion by naive T cells in an MLR. In addition, CD40L-dSIV-immunized mice exhibited stronger humoral and cell-mediated immune responses than dSIV-vaccinated animals. The results show that incorporating CD40L into the dSIV envelope significantly enhances immunogenicity. As a result, CD40L-dSIVs can be strong candidates for development of a safe and highly immunogenic AIDS vaccine.

Original languageEnglish (US)
Pages (from-to)1216-1227
Number of pages12
JournalJournal of Virology
Volume83
Issue number3
DOIs
StatePublished - Feb 2009

Fingerprint

Defective Viruses
Simian immunodeficiency virus
Simian Immunodeficiency Virus
CD40 Ligand
immune response
vaccines
AIDS Vaccines
Mixed Lymphocyte Culture Test
interleukin-12
dendritic cells
Interleukin-12
Viruses
ligands
Dendritic Cells
cytokines
lymphocytes
T-lymphocytes
Cytokines
Vesiculovirus
T-Lymphocytes

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Incorporation of CD40 ligand into the envelope of pseudotyped single-cycle simian immunodeficiency viruses enhances immunogenicity. / Lin, Fan Ching; Peng, Yue; Jones, Leslie A.; Verardi, Paulo H.; Yilma, Tilahun.

In: Journal of Virology, Vol. 83, No. 3, 02.2009, p. 1216-1227.

Research output: Contribution to journalArticle

Lin, Fan Ching ; Peng, Yue ; Jones, Leslie A. ; Verardi, Paulo H. ; Yilma, Tilahun. / Incorporation of CD40 ligand into the envelope of pseudotyped single-cycle simian immunodeficiency viruses enhances immunogenicity. In: Journal of Virology. 2009 ; Vol. 83, No. 3. pp. 1216-1227.
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