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Human cytomegalovirus (HCMV) pp65 (encoded by the UL83 gene) and glycoprotein B (gB, encoded by the UL55 gene) are primary immunodominant antigens used in the development of vaccines and immunotherapies against CMV infection (Arvin et al., 2004). The pp65 protein is the most abundant tegument protein and serves as a major target for the host's cellular immune response, specifically CD8+ cytotoxic T-lymphocytes (CTLs), which are crucial for controlling viral replication (Wills et al., 1996). Glycoprotein B is a Class III viral fusion protein essential for the virus to enter host cells by mediating the fusion of the viral envelope with host cell membranes (Isaacson et al., 2008). In many therapeutic contexts, a truncated version of gB is utilized, which typically involves the removal of the transmembrane and cytoplasmic domains to produce a soluble, secreted form of the protein that retains critical neutralizing epitopes (Pass et al., 2009). These two antigens are often combined in bivalent vaccines, such as DNA plasmids or viral vectors, to elicit a synergistic immune response comprising both neutralizing antibodies targeting gB and robust T-cell immunity targeting pp65 (Kharfan-Dabaja et al., 2018). This dual-targeting approach is particularly relevant for protecting immunocompromised individuals, such as hematopoietic stem cell transplant recipients, and for preventing congenital CMV transmission (Aldoss et al., 2020).
Induction of neutralizing antibodies against gB to prevent viral entry and stimulation of CD8+ and CD4+ T-cell responses against pp65 to eliminate infected cells.
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