DNA concentrations were converted to copy number/mL using the formula described by Fronhoffs et al.. Viral and cellular DNA copy numbers were converted to absolute weight for mutual comparison. The introduction of a new generation of sequencing technologies with high-throughput capacities has immensely impacted the field of genomics. Previous publications have provided a snapshot of the possible applications in the field of HCMV genomics and transcriptomics. We believe that the amplification, sequencing and analysis workflow that we present in this study can help to maximize the efficiency of sequencing HCMV strains in high-throughput. Given the large genetic background of HCMV, it could be interesting to routinely elucidate the complete sequence of strains that are used in mutational studies. This should no longer be considered as extremely laborious or costly. Additionally, the analysis of clinical HCMV isolates could assist in the refinement of the HCMV genetic map. It will provide a better knowledge of viral mutants and in which patient populations they are circulating. Finally, it could prove to be of value in the ongoing quest for genetic determinants of viral pathogenicity that has eluded scientists for more than a decade. To better manage health risks and costs, modern vaccines are no longer made from whole pathogens. Rather, they contain antigenic subunits that mainly provide the immune target to elicit memory responses against a broad spectrum of the pathogen’s strains and clades. For efficacy, most subunit vaccines require additional factors, so-called adjuvants; among them are pathogenassociated molecular patterns. Vaccine adjuvants can compensate for the lack of danger signals in subunit-based formulations, thereby improving the activation of innate and adaptive immune responses. Cyclic di-nucleotides are one such group of promising candidate adjuvants. They are signaling molecules which are involved in critical processes such as attachment and biofilm formation in prokaryotes and they control cell motility and proliferation states in the protozoon dictyostelium. Recently, an additional cyclic di-nucleotide, cyclic, was reported to activate the stimulator of interferon genes and to be synthesized by the mammalian enzyme cyclic GMP-AMP synthase upon stimulation with foreign DNA. Cyclic di-nucleotides such as bis–cyclic dimeric adenosine monophosphate, biscyclic dimeric guanosine monophosphate, and bis–cyclic dimeric inosine monophosphate proved to have immune modulatory activity in mice and humans. We and others have previously shown that c-di-AMP, cdi-GMP, and c-di-IMP act as potent adjuvants in immunization experiments with mice. We demonstrated that c-diAMP promotes humoral as well as cellular immune responses to model and vaccine antigens in mice immunized via the mucosal route. Immune modulation by c-di-AMP was observed to contribute to a balanced TH1/TH2/TH17 response.