VIRUS-LIKE PARTICLE DISPLAY TECHNOLOGY

capsid Virus-like particles (cVLPs) represent a significant advance in the development of subunit vaccines, combining high safety and efficacy. Their particulate nature and dense repetitive subunit organisation makes them ideal scaffolds for display of vaccine antigens. Traditional approaches for VLP-based antigen display require labor-intensive trial-and-error optimisation, and often fail to generate dense antigen display. Here we utilise the split-protein conjugation system to generate stable isopeptide bound antigen-cVLP complexes by simply mixing of the antigen and VLP components.

Example: COVID-19 RBD-cVLP vaccine

Platform Publications

Merel J Smit, MD, Adam F Sander, PhD, Maud B P A Ariaans, MD, Cyrielle Fougeroux, PhD, Constanze Heinzel, Rolf Fendel, PhD, Meral Esen, MD, Prof Peter G Kremsner, MD, Rob ter Heine, PhD, Prof Heiman F Wertheim, MD, Manja Idorn, PhD, Søren Riis Paludan, PhD, Alexander P Underwood, PhD, Alekxander Binderup, Santseharay Ramirez, PhD, Prof Jens Bukh, MD, Max Soegaard, PhD, Sayit M Erdogan, PhD, Tobias Gustavsson, PhD, Stine Clemmensen, PhD, Prof Thor G Theander, MD, Ali Salanti, PhD, Mette Hamborg, PhD,Willem A de Jongh, PhD, Matthew B B McCall, PhD, Morten A Nielsen, PhD, Prof Benjamin G Mordmüller, MD, on behalf of theCOUGH-1 trial study group. First-in-human use of a modular capsid virus-like vaccine platform: an open-label, non-randomised, phase 1 clinical trial of the SARS-CoV-2 vaccine ABNCoV2. doi: https://doi.org/10.1016/S2666-5247(22)00337-8

Ximba P, Chapman R, Meyers A, Margolin E, van Diepen M, Sander A, Woodward J, Moore P, Williamson AL, Rybicki E. Development of a synthetic nanoparticle vaccine presenting the HIV-1 envelope glycoprotein. Nanotechnology. 2022 Jul 26. doi: 10.1088/1361-6528/ac842c.

Linda van Oosten, Kexin Yan, Daniel Rawle, Thuy Le, Jort Altenburg, Cyrielle Fougeroux, Louise Goksøyr, Willem Adriaan de Jongh, Morten Nielsen, Adam F. Sander, Gorben Pijlman, and Andreas Suhrbier. An S1-nanoparticle vaccine protects against SARS-CoV-2 challenge in K18-hACE2 mice. J Virol. 2022 Jul 27;96(14):e0084422. doi: 10.1128/jvi.00844-22.

Jannick Prentoe, Christoph M. Janitzek, Rodrigo Velázquez-Moctezuma, Andreas Soerensen, Thomas Jørgensen, Stine Clemmensen, Vladislav Soroka, Susan Thrane, Thor Theander, Morten A. Nielsen, Ali Salanti, Jens Bukh, Adam F. Sander. Two-component Vaccine Consisting of Virus-Like Particles Displaying Hepatitis C Virus Envelope Protein 2 Oligomers. npjVvaccines (accepted). 2022.

Kara-Lee Aves, Christoph M Janitzek, Cyrielle E Fougeroux, Thor G Theander, Adam F Sander. Freeze-drying of a capsid virus-like particle-based platform allows stable storage of vaccines at ambient temperature. Pharmaceutics 14 (6), 1301. 2022

Goksøyr L, Funch AB, Okholm AK, Theander TG, de Jongh WA, Bonefeld CM, Sander AF. Preclinical Efficacy of a Capsid Virus-like Particle-Based Vaccine Targeting IL-1β for Treatment of Allergic Contact Dermatitis. Vaccines (Basel). 2022 May 23;10(5):828. doi: 10.3390/vaccines10050828

Volkmann A, Koopman G, Mooij P, Verschoor EJ, Verstrepen BE, Bogers WMJM, Idorn M, Paludan SR, Vang S, Nielsen MA, Sander AF, Schmittwolf C, Hochrein H, Chaplin P. A Capsid Virus-Like Particle-Based SARS-CoV-2 Vaccine Induces High Levels of Antibodies and Protects Rhesus Macaques. Front Immunol. 2022 Apr 5;13:857440. doi: 10.3389/fimmu.2022.857440. eCollection 2022.

Azad Farzadfard1,2, Jannik Nedergaard Pedersen1, Georg Meisl3, Arun Kumar Somavarapu1, Mehran Habibi-Rezaei2, Parvez Alam1,4, Louise Goksøyr5, Morten Agertoug Nielsen5, Adam Frederik Sander5, Tuomas P.J. Knowles3,6, Jan Skov Pedersen1,7, and Daniel Erik Otzen1,8*. The C-terminal tail of α-synuclein protects against aggregate replication but is critical for oligomerization. Communications Biology. 2022 Feb 10;5(1):123. doi: 10.1038/s42003-022-03059-8.2022.

van Oosten L, Altenburg JJ, Fougeroux C, Geertsema C, van den End F, Evers WAC, Westphal AH, Lindhoud S, van den Berg W, Swarts DC, Deurhof L, Suhrbier A, Le TT, Torres Morales S, Myeni SK, Kikkert M, Sander AF, de Jongh WA, Dagil R, Nielsen MA, Salanti A, Søgaard M, Keijzer TMP, Weijers D, Eppink MHM, Wijffels RH, van Oers MM, Martens DE, Pijlman GP. Two-Component Nanoparticle Vaccine Displaying Glycosylated Spike S1 Domain Induces Neutralizing Antibody Response against SARS-CoV-2 Variants. mBio. 2021 Oct 26;12(5):e0181321. doi: 10.1128/mBio.01813-21. Epub 2021 Oct 12. PMID: 34634927; PMCID: PMC8510518.

Jitthamstaporn S, Sander AF, Jacquet A. Virus-like particles displaying recombinant Der p 1 allergen to optimize IgG blocking antibody response. Allergy. 2021 Oct 7. doi: 10.1111/all.15129. Epub ahead of print. PMID: 34617292.

Fredsgaard L, Goksøyr L, Thrane S, Aves KL, Theander TG, Sander AF. Head-to-Head Comparison of Modular Vaccines Developed Using Different Capsid Virus-Like Particle Backbones and Antigen Conjugation Systems. Vaccines (Basel). 2021 May 21;9(6):539. doi: 10.3390/vaccines9060539. PMID: 34063871; PMCID: PMC8224050.

Janitzek CM, Carlsen PHR, Thrane S, Khanna VM, Jakob V, Barnier-Quer C, Collin N, Theander TG, Salanti A, Nielsen MA, Sander AF. The Immunogenicity of Capsid-Like Particle Vaccines in Combination with Different Adjuvants Using Different Routes of Administration. Vaccines (Basel). 2021 Feb 6;9(2):131. doi: 10.3390/vaccines9020131. PMID: 33562114; PMCID: PMC7915698.

Fougeroux C, Goksøyr L, Idorn M, Soroka V, Myeni SK, Dagil R, Janitzek CM, Søgaard M, Aves KL, Horsted EW, Erdoğan SM, Gustavsson T, Dorosz J, Clemmensen S, Fredsgaard L, Thrane S, Vidal-Calvo EE, Khalifé P, Hulen TM, Choudhary S, Theisen M, Singh SK, Garcia-Senosiain A, Van Oosten L, Pijlman G, Hierzberger B, Domeyer T, Nalewajek BW, Strøbæk A, Skrzypczak M, Andersson LF, Buus S, Buus AS, Christensen JP, Dalebout TJ, Iversen K, Harritshøj LH, Mordmüller B, Ullum H, Reinert LS, de Jongh WA, Kikkert M, Paludan SR, Theander TG, Nielsen MA, Salanti A, Sander AF. Capsid-like particles decorated with the SARS-CoV-2 receptor-binding domain elicit strong virus neutralization activity. Nat Commun. 2021 Jan 12;12(1):324. doi: 10.1038/s41467-020-20251-8. PMID: 33436573; PMCID: PMC7804149.

Thrane S, Aves KL, Uddbäck IEM, Janitzek CM, Han J, Yang YR, Ward AB, Theander TG, Nielsen MA, Salanti A, Thomsen AR, Christensen JP, Sander AF. A Vaccine Displaying a Trimeric Influenza-A HA Stem Protein on Capsid-Like Particles Elicits Potent and Long-Lasting Protection in Mice. Vaccines (Basel). 2020 Jul 15;8(3):389. doi: 10.3390/vaccines8030389. PMID: 32679905; PMCID: PMC7564254.

Harmsen C, Turner L, Thrane S, Sander AF, Theander TG, Lavstsen T. Immunization with virus-like particles conjugated to CIDRα1 domain of Plasmodium falciparum erythrocyte membrane protein 1 induces inhibitory antibodies. Malar J. 2020 Mar 30;19(1):132. doi: 10.1186/s12936-020-03201-z. PMID: 32228596; PMCID: PMC7106694.

Aves KL, Goksøyr L, Sander AF. Advantages and Prospects of Tag/Catcher Mediated Antigen Display on Capsid-Like Particle-Based Vaccines. Viruses. 2020 Feb 6;12(2):185. doi: 10.3390/v12020185. PMID: 32041299; PMCID: PMC7077247.

Soongrung T, Mongkorntanyatip K, Peepim T, Jitthamstaporn S, Pitakpolrat P, Kaewamatawong T, Janitzek CM, Thrane S, Sander AF, Jacquet A. Virus-like particles displaying major house dust mite allergen Der p 2 for prophylactic allergen immunotherapy. Allergy. 2020 May;75(5):1232-1236. doi: 10.1111/all.14096. Epub 2020 Feb 5. PMID: 31701528.

Singh SK, Thrane S, Chourasia BK, Teelen K, Graumans W, Stoter R, van Gemert GJ, van de Vegte-Bolmer MG, Nielsen MA, Salanti A, Sander AF, Sauerwein RW, Jore MM, Theisen M. Pf/is230 and Pfis48/45 Fusion Proteins Elicit Strong Transmission-Blocking Antibody Responses Against Plasmodium falciparum. Front Immunol. 2019 Jun 5;10:1256. doi: 10.3389/fimmu.2019.01256. PMID: 31231386; PMCID: PMC6560166.

Janitzek CM, Peabody J, Thrane S, H R Carlsen P, G Theander T, Salanti A, Chackerian B, A Nielsen M, Sander AF. A proof-of-concept study for the design of a VLP-based combinatorial HPV and placental malaria vaccine. Sci Rep. 2019 Mar27;9(1):5260. doi: 10.1038/s41598-019-41522-5. PMID: 30918267; PMCID: PMC6437161.

Sander AF, Lollini PL. Virus-like antigen display for cancer vaccine development, what is the potential? Expert Rev Vaccines. 2018 Apr;17(4):285-288. doi: 10.1080/14760584.2018.1455505. Epub 2018 Mar 30. PMID: 29560746.

Palladini A, Thrane S, Janitzek CM, Pihl J, Clemmensen SB, de Jongh WA, Clausen TM, Nicoletti G, Landuzzi L, Penichet ML, Balboni T, Ianzano ML, Giusti V, Theander TG, Nielsen MA, Salanti A, Lollini PL, Nanni P, Sander AF. Virus-like particle display of HER2 induces potent anti-cancer responses. Oncoimmunology. 2018 Jan 5;7(3):e1408749. doi: 10.1080/2162402X.2017.1408749. PMID: 29399414; PMCID: PMC5790387.

Singh SK, Thrane S, Janitzek CM, Nielsen MA, Theander TG, Theisen M, Salanti A, Sander AF. Improving the malaria transmission-blocking activity of a Plasmodium falciparum 48/45 based vaccine antigen by SpyTag/SpyCatcher mediated virus-like display. Vaccine. 2017 Jun 27;35(30):3726-3732. doi: 10.1016/j.vaccine.2017.05.054. Epub 2017 May 31. PMID: 28578824.

Janitzek CM, Matondo S, Thrane S, Nielsen MA, Kavishe R, Mwakalinga SB, Theander TG, Salanti A, Sander AF. Bacterial superglue generates a full-length circumsporozoite protein virus-like particle vaccine capable of inducing high and durable antibody responses. Malar J. 2016 Nov 8;15(1):545. doi: 10.1186/s12936-016-1574-1. PMID: 27825348; PMCID: PMC5101663.

Thrane S, Janitzek CM, Matondo S, Resende M, Gustavsson T, de Jongh WA, Clemmensen S, Roeffen W, van de Vegte-Bolmer M, van Gemert GJ, Sauerwein R, Schiller JT, Nielsen MA, Theander TG, Salanti A, Sander AF. Bacterial superglue enables easy development of efficient virus-like particle based vaccines. J Nanobiotechnology. 2016 Apr 27;14:30. doi: 10.1186/s12951-016-0181-1. PMID: 27117585; PMCID: PMC4847360.

Thrane S, Janitzek CM, Agerbæk MØ, Ditlev SB, Resende M, Nielsen MA, Theander TG, Salanti A, Sander AF. A Novel Virus-Like Particle Based Vaccine Platform Displaying the Placental Malaria Antigen VAR2CSA. PLoS One. 2015 Nov 23;10(11):e0143071. doi: 0.1371/journal.pone.0143071. PMID: 26599509; PMCID: PMC4657905.

Chapter: “Design and purification of Tag/Catcher AP205-based capsid virus-like particle vaccines”. Authors: Kara-Lee Aves and Adam F. Sander for "Therapeutic Proteins: Methods and Protocols" published in Methods in Molecular Biology, Springer Nature (in press).

Louise Goksøyr, Magdalena Skrzypczak, Maureen Sampson, Morten A. Nielsen, Ali Salanti, Thor G. Theander, Alan T. Remaley, Willem Adriaan de Jongh, Adam F. Sander. A capsid-based virus-like particle vaccine displaying full-length PCSK9 lowers plasma PCSK9 levels compared to vaccines displaying PCSK9-derived peptide antigens. Nanomedicine (in review).

Ruzzi F, Palladini A, Clemmensen S, Strøbæk A, Buijs N, Domeyer T, Dorosz J, Soroka V, Grzadziela D, Rasmussen CJ, Nielsen IB, Soegaard M, Semprini MS, Scalambra L, Angelicola S, Landuzzi L, Lollini P-L, Thorn M. Prevention and Therapy of Metastatic HER-2+ Mammary Carcinoma with a Human Candidate HER-2 Virus-like Particle Vaccine. Biomedicines. 2022; 10(10):2654