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Therapeutic vaccines for herpesviruses
Jeffrey I. Cohen
Jeffrey I. Cohen
Published May 1, 2024
Citation Information: J Clin Invest. 2024;134(9):e179483. https://doi.org/10.1172/JCI179483.
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Review

Therapeutic vaccines for herpesviruses

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Abstract

Herpesviruses establish latent infections, and most reactivate frequently, resulting in symptoms and virus shedding in healthy individuals. In immunocompromised patients, reactivating virus can cause severe disease. Persistent EBV has been associated with several malignancies in both immunocompromised and nonimmunocompromised persons. Reactivation and shedding occur with most herpesviruses, despite potent virus-specific antibodies and T cell immunity as measured in the blood. The licensure of therapeutic vaccines to reduce zoster indicates that effective therapeutic vaccines for other herpesviruses should be feasible. However, varicella-zoster virus is different from other human herpesviruses in that it is generally only shed during varicella and zoster. Unlike prophylactic vaccines, in which the correlate of immunity is antibody function, T cell immunity is the correlate of immunity for the only effective therapeutic herpesvirus vaccine–zoster vaccine. While most studies of therapeutic vaccines have measured immunity in the blood, cellular immunity at the site of reactivation is likely critical for an effective therapeutic vaccine for certain viruses. This Review summarizes the status of therapeutic vaccines for herpes simplex virus, cytomegalovirus, and Epstein-Barr virus and proposes approaches for future development.

Authors

Jeffrey I. Cohen

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Figure 1

Viral components for a therapeutic vaccine on infected cells.

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Viral components for a therapeutic vaccine on infected cells.
(A) Herpes...
(A) Herpes simplex virus– (glycoprotein D [gD], gB, immediate-early [IE] ICP4, UL46, and UL49 tegument proteins), (B) CMV- (IE1, IE2, pp65 tegument protein, gB), and (C) EBV-infected cells (IE BZLF1 protein, LMP2, EBNA1). Proteins are shown based on their location in infected cells, but viral peptides are presented on the surface of the cells with MHC class I or II.

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

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