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CD4+ T cell–independent DNA vaccination against opportunistic infections
Mingquan Zheng, … , Qiu Zhong, Jay K. Kolls
Mingquan Zheng, … , Qiu Zhong, Jay K. Kolls
Published December 1, 2005
Citation Information: J Clin Invest. 2005;115(12):3536-3544. https://doi.org/10.1172/JCI26306.
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Research Article Virology Article has an altmetric score of 3

CD4+ T cell–independent DNA vaccination against opportunistic infections

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Abstract

Depletion or dysfunction of CD4+ T lymphocytes profoundly perturbs host defenses and impairs immunogenicity of vaccines. Here, we show that plasmid DNA vaccination with a cassette encoding antigen (OVA) and a second cassette encoding full-length CD40 ligand (CD40L), a molecule expressed on activated CD4+ T lymphocytes and critical for T cell helper function, can elicit significant titers of antigen-specific immunoglobulins in serum and Tc1 CD8+ T cell responses in CD4-deficient mice. To investigate whether this approach leads to CD4+ T cell–independent vaccine protection against a prototypic AIDS-defining infection, Pneumocystis (PC) pneumonia, we used serum from mice vaccinated with PC-pulsed, CD40L-modifed DCs to immunoprecipitate PC antigens. Kexin, a PC antigen identified by this approach, was used in a similar DNA vaccine strategy with or without CD40L. CD4-deficient mice receiving DNA vaccines encoding Kexin and CD40L showed significantly higher anti-PC IgG titers as well as opsonic killing of PC compared with those vaccinated with Kexin alone. Moreover, CD4-depleted, Kexin-vaccinated mice showed a 3-log greater protection in a PC challenge model. Adoptive transfer of CD19+ cells or IgG to SCID mice conferred protection against PC challenge, indicating a role of humoral immunity in the protection. The results of these studies show promise for CD4-independent vaccination against HIV-related or other opportunistic pathogens.

Authors

Mingquan Zheng, Alistair J. Ramsay, Myles B. Robichaux, Karen A. Norris, Corrine Kliment, Christopher Crowe, Rekha R. Rapaka, Chad Steele, Florencia McAllister, Judd E. Shellito, Luis Marrero, Paul Schwarzenberger, Qiu Zhong, Jay K. Kolls

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Figure 4

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Proteomics of PC antigens. (A) Immunoprecipitation of PC antigens after ...
Proteomics of PC antigens. (A) Immunoprecipitation of PC antigens after DC-based vaccination in mice with 1 antigen identified at 55 kDa. N-terminal sequencing and tandem MS analysis of this antigen showed greater than 85% homology with Kexin. M denotes molecular weight marker. (B) Typhoon images of 2D gels of Cy5-labeled naive serum (left) or immunoprecipitated PC antigens (right). Proteins were separated within pH 5–8 for the first dimension. Boxes indicate proteins that were analyzed by matrix-assisted laser desorption/ionization (MALDI) TOF/TOF mass spectrometry.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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Referenced in 4 patents
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