This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Objective: To determine whether post-exposure immunization of monkeys already infected with rhesus cytomegalovirus (RhCMV) can alter the frequency of viral shedding at mucosal surfaces. Preconceptional immunity to HCMV does not fully protect against maternal reinfection with HCMV and transplacental transmission of virus to the fetus. The frequency of fetal sequelae following either reactivation/reinfection of the mother may be greater than once believed. These findings highlight that our understanding of the correlates of protective immunity to HCMVare incomplete. Resolution of these issues is paramount to design effective vaccines. Maternal immune responses to HCMV are protective because clinical outcomes in the mother are rare. Immune responses are not protective because HCMV can disseminate in the presence of antiviral immunity. Reactivated virus can potentially be transmitted horizontally and/or vertically across the placenta. It is the inability of antiviral immunity to restrict HCMV replication that defines the limitation of the immune response. Vaccine strategies need to include some seropositive individuals to achieve two potential goals. One goal is to reduce pathological outcomes of endogenously or exogenously acquired virus. The other is a reduction in the frequency of HCMV reactivation. The following Aims will test whether post-exposure immunization reduces RhCMV load in mucosal fluids. (1) Screening of seropositive animals for RhCMV shedding in mucosal fluids. (2) Immunization of animals with plasmid vectors for RhCMV antigens. (3) Post-immunization assessment of RhCMV shedding. The premise is that post-exposure immunization can stimulate greater immunological control of cells producing infectious virions. Substantiation of the hypothesis will validate expansion of HCMV vaccine strategies to include populations of seropositive individuals and provide insight into the relationships of early virus-host interactions and chronic outcomes.
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