Technology

oligoDOMTM: A Novel Proprietary Nanoparticles Technology specifically designed to trigger superior T-cell responses, in addition to strong and sustained B-cell responses

The core concept

Nanoparticles self-assemble to present key immunogenic structures of a specific virus in repetition to induce an immune response.

Improving and surpassing the Nanoparticles technology

oligoDOMTM has been uniquely designed to increase the T-cell immune response to the native antigen thanks to a specific signal sequence targeting and activating cells from the immune system.
OligoDOMTM was pioneered by our co-founder, Fergal Hill, whose vision and expertise were instrumental in its development.

Building upon the established Nanoparticles concept

Like other self-assembling nanoparticles technologies, oligoDOMTM also triggers a strong B-cell response by transforming a small, non-immunogenic, native antigen into a large nanoparticle which is easily detected by the immune system, exposing multiple copies of the native antigen.
When associated to an antigen, oligoDOMTM forms a unique self-assembling nanoparticles, exposing multiple copies of full-length antigens

Given its design and mechanism of action, the oligoDOMTM technology platform is highly versatile and can be used with different antigens, as well as within different vaccine technologies such as recombinant proteins, or mRNA technology, leading to multiple value generation opportunities.

Osivax is developing several vaccine candidates, 3 of which are already in clinical phase (OVX033, OVX836 and PANHPVAX). As of today the oligoDOMTM technology has been evaluated in 7 clinical trials with more than 1,200 subjects.
Osivax is also expanding its portfolio in other areas investigating the potential synergies with other innovative vaccine technologies (like adjuvants or mRNA).

Preventing the Spread of constantly mutating Global Infectious Diseases

Viruses such as influenza constantly mutate making it difficult to accurately predict each year’s virus variants. Most conventional vaccines target highly mutating surface structures, a method that provides suboptimal protection, especially in vulnerable populations such as the elderly. Osivax is pioneering a universal vaccine which will uniquely empower both the B-cell and the T-cell immune responses. Osivax will combine its best-in-class T-cell component with conventional flu vaccines to fully empower both arms of the immune system. Thanks to its oligoDOMTM technology, Osivax’ vaccines can trigger a T-cell immune response that targets internal and invariant parts of a virus to provide universal protection against both current and future virus strains or variants.

The innovative oligoDOMTM technology, an improved self-assembling Nanoparticles approach, targets internal and invariant parts of viruses in a very powerful way

References

Immunogenicity, safety, and preliminary efficacy evaluation of OVX836, a nucleoprotein-based universal influenza A vaccine candidate: a randomised, double-blind, placebo-controlled, phase 2a trial.
Leroux-Roels I, Willem P, Waerlop G, Janssens Y, Tourneur J, De Boever F, Bruhwyler J, Alhatemi A, Jacobs B, Nicolas F, Leroux-Roels G, Le Vert A.
The Lancet ID., July 2023. doi: 10.1016/S1473-3099(23)00351-1

Randomized, Double-Blind, Reference-Controlled, Phase 2a Study Evaluating the Immunogenicity and Safety of OVX836, A Nucleoprotein-Based Influenza Vaccine.
Leroux-Roels I, Waerlop G, Tourneur J, De Boever F, Maes C, Bruhwyler J, Guyon-Gellin D, Moris P, Del Campo J, Willems P, Leroux-Roels G, Le Vert A, Nicolas F.
Front. Immunol., April 2022. doi: 10.3389/fimmu.2022.852904

Randomized Placebo-Controlled, Dose-Escalating Study to Evaluate OVX836, a Nucleoprotein-Based Influenza Vaccine: Intramuscular Results.
Withanage K, De Coster I, Cools N, Viviani S, Tourneur J, Chevandier M, Lambiel M, Willems P, Le Vert A, Nicolas F, Van Damme P.
The Journal of Infectious Diseases, Oct. 2021. doi: 10.1093/infdis/jiab532

OVX836 Heptameric Nucleoprotein Vaccine Generates Lung Tissue-Resident Memory CD8+ T-Cells for Cross-Protection Against Influenza. 
Del Campo J, Bouley J, Chevandier M, Rousset C, Haller M, Indalecio A, Guyon-Gellin D, Le Vert A, Hill F, Djebali S, Leverrier Y, Marvel J, Combadière B and Nicolas F.
Front. Immunol., June 2021. doi: 10.3389/fimmu.2021.678483

OVX836 a recombinant nucleoprotein vaccine inducing cellular responses and protective efficacy against multiple influenza A subtypes. 
Del Campo J, Pizzorno A, Djebali S, Bouley J, Haller M, Pérez-Vargas J, Lina B, Boivin G, Hamelin M-E, Nicolas F, Le Vert A, Leverrier Y, Rosa-Calatrava M, Marvel J, Hill F.
npj Vaccines, Jan. 2019. doi: 10.1038/s41541-019-0098-4.

OVX033, a nucleocapsid-based vaccine candidate provides broad-spectrum protection against SARS-CoV-2 variants in a hamster challenge model
Primard C, Monchâtre-Leroy E, Del Campo J, Valsesia S, Nikly E, Chevandier M, Boué F, Servat A, Wasniewski M, Picard-Meyer E, Courant T, Collin N, Salguero FJ, Le Vert A, Guyon-Gellin D, Nicolas F.
Front. Immunol., 19 June 2023. doi: 10.3389/fimmu.2023.1188605

Combined prophylactic and therapeutic immune responses against human papillomaviruses induced by a thioredoxin-based L2-E7 nanoparticle vaccine. 
Zhao X, Yang F,  Mariz F,  Osen W,  Bolchi A,  Ottonello S,  Müller M.
PLoS Pathog., 2020 Sep.  e1008827. doi: 10.1371/journal.ppat.1008827

Minor capsid protein L2 polytope induces broad protection against oncogenic and mucosal human papillomaviruses.
Pouyanfard S, Spagnoli G, Bulli L, Balz K, Yang F, Odenwald C, Seitz H, Mariz FC, Bolchi A, Ottonello S, Müller M.
J Virol., 2018 Feb. 92:e01930-17. doi: 10.1128/JVI.01930-17.

Broadly neutralizing antiviral responses induced by a single-molecule HPV vaccine based on thermostable thioredoxin-L2 multiepitope nanoparticles.
Spagnoli G, Pouyanfard S, Cavazzini D, Canali E, Maggi S, Tommasino M, Bolchi A, Müller M, Ottonello S.
Sci Rep. 2017; 7: 18000. Published online 2017 Dec 21. doi: 10.1038/s41598-017-18177-1.

SnoopLigase peptide-peptide conjugation enables modular vaccine assembly 
Andersson AC, Buldun CM, Pattinson DJ, Draper SJ, Howarth M.
Sci Rep. 2019 Mar 15;9(1):4625. doi: 10.1038/s41598-019-40985-w.

Combination of RTS,S and Pfs25-IMX313 Induces a Functional Antibody Response Against Malaria Infection and Transmission in Mice. 
Brod F, Miura K, Taylor I, Li Y, Marini A, Salman AM, Spencer AJ, Long CA, Biswas S.
Front Immunol., 2018 Dec 4;9:2780. doi: 10.3389/fimmu.2018.02780.

​Dual Plug-and-Display Synthetic Assembly Using Orthogonal Reactive Proteins for Twin Antigen Immunization. 
Brune KD, Buldun CM, Li Y, Taylor IJ, Brod F, Biswas S, Howarth M.
Bioconjug Chem., 2017 May 17;28(5):1544-1551. doi: 10.1021/acs.bioconjchem.7b00174.

A HIV-Tat/C4-binding protein chimera encoded by a DNA vaccine is highly immunogenic and contains acute EcoHIV infection in mice.
Tomusange K, Wijesundara D, Gummow J, Garrod T, Li Y, Gray L, Churchill M, Grubor-Bauk B, Gowans EJ.
Sci Rep. 2016 Jun 30;6:29131. doi: 10.1038/srep29131.

Enhancing immunogenicity and transmission-blocking activity of malaria vaccines by fusing Pfs25 to IMX313 multimerization technology.
Li Y, Leneghan DB, Miura K, Brian IJ, Dicks MD, Fyfe AJ, Zakutansky SE, De Cassan S, Long CA, Draper SJ, Hill AV, Hill F, Biswas S.
Sci Rep. 2016 January 8;6:18848. doi: 10.1038/srep18848.

T Cell Responses Induced by Adenoviral Vectored Vaccines Can Be Adjuvanted by Fusion of Antigen to the Oligomerization Domain of C4b-Binding Protein.
Forbes EK, de Cassan SC, Llewellyn D, Biswas S, Goodman AL, Cottingham MG, Long CA, Pleass RJ, Hill AV, Hill F, Simon J. Draper.
PLoS ONE., 2012 September;7(9):e44943. doi:10.1371/journal.pone.0044943.

Fusion of the Mycobacterium tuberculosis antigen 85A to an oligomerization domain enhances its immunogenicity in both mice and non-human primates.
Spencer AJ, Hill F, Honeycutt JD, Cottingham MG, Bregu M, Rollier CS, Furze J, Draper SJ, Søgaard KC, Gilbert SC, Wyllie DH, Hill AVS.
PLoS ONE. 2012 March;7(3): e33555. doi:10.1371/journal.pone.0033555.

Immunocontraception in male feral swine treated with a recombinant gonadotropin-releasing hormone vaccine.
Campbell TA, Garcia MR, Miller LA, Ramirez MA, Long DB, Marchand JB, Hill F. 
JSHAP., May 2010; 18(3):118-124​.

The oligomerization domain of C4-binding protein (C4bp) acts as an adjuvant, and the fusion protein comprised of the 19-kilodalton merozoite surface protein 1 fused with the murine C4bp domain protects mice against malaria.
Ogun SA, Dumon-Seignovert L, Marchand JB, Holder AA, Hill F.
Infect Immun., 2008 Aug;76(8):3817-3823. doi:10.1128/IAI.01369-07.

Effective induction of high-titer antibodies by viral vector vaccines.
Draper SJ, Moore AC, Goodman AL, Long CA, Holder AA, Gilbert SC, Hill F, Hill AV.
Nat Med., 2008 Aug;14(8):819-821. doi: 10.1038/nm.1850.