Dual-approach to identify immunogenic cytomegalovirus antigens for vaccine design

Abstract

Abstract Human cytomegalovirus (CMV), a herpesvirus that infects most of the global population remains without a licensed vaccine. Although natural infection elicits an immune response that confers partial protection, the development of an effective CMV vaccine has proven challenging. Despite multiple vaccine attempts, the complex interactions between CMV and the host immune system have hindered successful vaccine design. In this study, we utilize the naturally acquired CMV-specific immunity of solid organ transplant (SOT) recipients to identify viral antigens recognized by antibodies present in patient sera. Using Western blot and ELISA in combination with proteomic analyses, we identified five highly immunogenic CMV proteins: UL44, UL57, UL83, UL132 and RL11. While UL44, UL57 and UL83 are well-established immunodominant antigens, hereby validating our strategy, UL132 and RL11 emerged as additional highly immunogenic targets. The detection of antibodies against these CMV antigens in patients with a protective CMV-specific immune response underscores their immunogenicity and supports their potential relevance for vaccine development. Taken together, these findings identify CMV antigens of potential interest for vaccine research.