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
Phase 3 validated
Tag/Catcher cVLP display platform
AdaptVac's iso-peptide display platform utilises our proprietary MoonCatcher/Tag pair.
Furthermore, the cVLP is based on Tag or Catcher fused Bacteriophage AP205 capsid protein, which spontaneously forms a capsid Virus-Like Particle during production in E.coli.
MoonCatcher and AP205 have now been through Phase 3 clinical testing in our ABNCoV2 COVID-19 vaccine program. Demonstrating safety and regulatory acceptance for our platform.
A true vaccine platform
technology
cVLP display has consistently demonstrated improved immunogenicity for a wide range of antigens. These have ranged from Malaria and Flu, to Gonorrhoea and even Cancer self-antigens.
Platform Publications
Merel J Smit, et al. 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.
Lancet Microbe. doi: https://doi.org/10.1016/S2666-5247(22)00337-8
Ximba P, et al.. 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, et al. 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, et al. Two-component Vaccine Consisting of Virus-Like Particles Displaying Hepatitis C Virus Envelope Protein 2 Oligomers. npjVvaccines (accepted). 2022.
Kara-Lee Aves, et al. 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, et al. Preclinical Efficacy of a Capsid Virus-like Particle-Based Vaccine Targeting IL-1β for Treatment of Allergic Contact Dermatitis.
Vaccines. 2022 May 23;10(5):828. doi:10.3390/vaccines10050828
Volkmann A, et al.. 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
Azad Farzadfard at al.. 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 et al. 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 et al 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 et al.. 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 et al. The Immunogenicity of Capsid-Like Particle Vaccines in Combination with Different Adjuvants Using Different Routes of Administration.
Vaccines. 2021 Feb 6;9(2):131. doi: 10.3390/vaccines9020131. PMID: 33562114; PMCID: PMC7915698.
Fougeroux et al. 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 et al. A Vaccine Displaying a Trimeric Influenza-A HA Stem Protein on Capsid-Like Particles Elicits Potent and Long-Lasting Protection in Mice.
Vaccines. 2020 Jul 15;8(3):389. doi: 10.3390/vaccines8030389. PMID: 32679905; PMCID: PMC7564254.
Harmsen et al. 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 et al. 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 et al. 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 et al. 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 et al. 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 et al. 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 et al.. 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 et al. 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 et al. 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 et al. 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 et al. 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 et al. 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 et al. Prevention and Therapy of Metastatic HER-2+ Mammary Carcinoma with a Human Candidate HER-2 Virus-like Particle Vaccine. Biomedicines. 2022; 10(10):2654