**5. Conclusions and Future Directions**

We described a large variety of systems to generate both VLPs and NPs. Self-assembling scaffolds have been used to present complex glycoprotein antigens and for vaccination studies against influenza [104], HIV [113,120–123], Epstein–Barr virus [89], and RSV [112]. In all cases, antigen immunogenicity was increased by multivalent presentation and in some cases, an epitope focusing effect could be observed. The rise of computational design to generate novel self-assembling proteins has now paved the way for new possibilities to display antigens without limitation in term of quantity or oligomeric state of the antigen. HCMV is still the principal viral cause of congenital malformations. About one quarter of infants infected by HCMV in utero will develop severe sequelae including microcephaly, sensorineural hearing and vision loss, or cognitive delay [1,6]. The recent identification of key HCMV antigenic targets for both humoral and cellular immune responses and the capacity to display and encapsulate proteins or nucleic acids (RNAs) on VLPs/NPs is likely to generate improved vaccine candidates able to redirect the immune response against specific targets.

**Author Contributions:** M.P. and L.P. conceptualized and wrote the review. All authors have read and agreed to the published version of the manuscript.

**Funding:** This work was supported by the Novartis Foundation for Medical–Biological Research, Novartis grant (application #19B116 to LP).

**Acknowledgments:** The authors acknowledge Mathilde Foglierini and Jessica Marcandalli for critical reading and helpful comments on the manuscript.

**Conflicts of Interest:** The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.
