Delivering adjuvants and antigens in separate nanoparticles eliminates the need of physical linkage for effective vaccination.

Mohsen, Mona O; Gomes, Ariane C; Cabral-Miranda, Gustavo; Krüger, Caroline Claire; Leoratti, Fabiana M S; Stein, Jens Volker; Bachmann, Martin (2017). Delivering adjuvants and antigens in separate nanoparticles eliminates the need of physical linkage for effective vaccination. Journal of controlled release, 251, pp. 92-100. Elsevier 10.1016/j.jconrel.2017.02.031

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DNA rich in unmethylated CG motifs (CpGs) engage Toll-Like Receptor 9 (TLR-9) in endosomes and are well described stimulators of the innate and adaptive immune system. CpGs therefore can efficiently improve vaccines' immunogenicity. Packaging CpGs into nanoparticles, in particular into virus-like particles (VLPs), improves the pharmacological characteristics of CpGs as the protein shell protects them from DNAse activity and delivers the oligomers to the endosomal compartments of professional antigen presenting cells (APCs). The current consensus in packaging and delivering CpGs in VLP-based vaccines is that both adjuvants and antigens should be kept in close proximity (i.e. physically linked) to ensure delivery of antigens and adjuvants to the same APCs. In the current study, we harness the draining properties of the lymphatic system and show that also non-linked VLPs are efficiently co-delivered to the same APCs in lymph nodes. Specifically, we have shown that CpGs can be packaged in one VLP and mixed with another VLP displaying the antigen prior to administration in vivo. Both VLPs efficiently reached the same draining lymph node where they were taken up and processed by the same APCs, namely dendritic cells and macrophages. This resulted in induction of specific CTLs producing cytokines and killing target cells in vivo at levels seen when using VLPs containing both CpGs and chemically conjugated antigen. Thus, delivery of antigens and adjuvants in separate nanoparticles eliminates the need of physical conjugation and thus can be beneficial when designing precision medicine VLP-based vaccines or help to re-formulate existing VLP vaccines not naturally carrying immunostimulatory sequences.

Item Type:

Journal Article (Original Article)


04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Rheumatology, Clinical Immunology and Allergology
04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Institute for Immunology [discontinued]
04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Krüger, Caroline Claire; De Souza Leoratti, Fabiana Maria; Stein, Jens Volker and Bachmann, Martin


600 Technology > 610 Medicine & health








Jens Volker Stein

Date Deposited:

04 Jul 2018 15:43

Last Modified:

23 Oct 2019 05:03

Publisher DOI:


PubMed ID:


Uncontrolled Keywords:

Conventional dendritic cells (cDCs) Cytotoxic T-Lymphocytes (CTLs) Oligonucleotides rich in non-methylated CG motifs (CpGs) Plasmacytoid dendritic cells (pDCs) Toll-Like Receptor-9 (TLR-9) Virus-like particles (VLPs)




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