COVID-19 VLP Vaccine

Developed by Prof. Mayda Gürsel (METU), Prof. İhsan Gürsel (Bilkent University) and their research teams.

VLP vaccine is supported under the TÜBİTAK COVID-19 Vaccine and Medicine Platform and developed as part of a joint project of METU and Bilkent University. As of June 26, 2021, the vaccine started to be applied to volunteers in the Phase-2 stage. Phase-2 will be carried out in 3 centers: Ankara Oncology Education and Research Hospital, Kocaeli University Faculty of Medicine, and Yedikule Chest Diseases Hospital with approximately 330 volunteers. A version of the vaccine developed against the British mutant will also be included in the trials. Those who want to volunteer can apply by filling out the "volunteer form" available at and


VLP stands for virus-like particles. They consist of viral structural proteins such as envelope and capsid proteins that assemble in vitro expression systems to form nanoparticles mimicking the conformation of viruses [1]. As VLPs do not carry any genetic material, they do not replicate and are thus considered a safe choice for vaccine development. VLP-based vaccines against the human papillomavirus (HPV) and hepatitis B virus (HBV) infections have already been approved by the FDA and are being used for prophylactic protection [2]. Other VLP vaccine candidates against the influenza virus or HIV are currently being evaluated in clinical trials [2, 3].

In addition to their safety, VLP-based vaccines present another advantage in adaptive immune activation over other vaccine candidates. The adaptive immune system is responsible for specific antibody production by B-cells to neutralize the pathogen and for activation of cellular responses that are carried out by cytotoxic and helper T-cells [1]. Once VLP vaccines are injected into the tissue, their conformation allows the robust activation of multiple B-cell receptors, increasing the cells’ capacity for antibody production. Furthermore, cells infected by an intracellular pathogen present their foreign proteins on their outer surface, which can be recognized by cytotoxic T-cells, thereby activating them to kill the infected cell [4]. By incorporating multiple viral structural proteins in VLPs, more epitopes specific to the virus are introduced to the immune system that can become potential targets for cytotoxic T-cells. Traditional vaccines such as inactivated virus vaccines also contain whole virus components. However, they might damage antigenic epitopes in the inactivation process and limit their recognition by B-cell and T-cell receptors.

Our VLP formulated vaccine candidate against SARS-CoV-2 is based on the expression and assembly of four structural viral proteins known as spike (S), membrane glycoprotein (M), envelope (E), and nucleocapsid (N). We transiently transfect suspension-adapted HEK293 cells and isolate VLPs from the cell culture media by multimodal chromatography purification. VLPs are then adjuvanted with both CpG oligodeoxynucleotides (ODN) and aluminum hydroxide. CpG ODNs enhance antiviral immune responses by polarizing the immune balance towards an antiviral helper T-cell subtype (Th1) [5, 6]. Th1 cells are capable of releasing IFN-γ, which is a limiting cytokine for viral replication but activatory for other immune cell recruitment such as macrophages or neutrophils. Aluminum hydroxide is a known potent adjuvant that has been used for decades in vaccine research and development [7]. Although aluminum induces high titers of antibody production, it also guides the polarization towards another subtype known as Th2, resulting in a different cytokine milieu than Th1. By formulating VLPs with both CpG ODN and aluminum, our vaccine carries the potential benefits of high antibody titers and Th1-balanced cellular immunity response.

We have started human immunizations within a phase I clinical trial (NCT04818281) specific to the Wuhan strain of the virus and advanced to phase II (NCT04962893) in three groups that are composed of immunizations against only Wuhan, only alpha (UK variant), Wuhan (1st dose) followed by alpha (2nd dose) strains. We are currently in the process of delta plus variant-based VLP production as preparation for the phase III clinical trial. A research article on preclinical studies of our VLP-based vaccine with the title “Development and Preclinical Evaluation of Virus Like Particle Vaccine Against COVID-19 Infection” is published in the Allergy journal.


[1]. Nooraei S, Bahrulolum H, Hoseini ZS, Katalani C, Hajizade A, Easton AJ, et al. Virus-like particles: preparation, immunogenicity and their roles as nanovaccines and drug nanocarriers. J Nanobiotechnology 2021 191. 2021;19:1–27.
[2]. Roldão A, Mellado MCM, Castilho LR, Carrondo MJ, Alves PM. Virus-like particles in vaccine development. Expert Rev Vaccines. 2014;9:1149–76.
[3]. Garg H, Mehmetoglu-Gurbuz T, Joshi A. Virus Like Particles (VLP) as multivalent vaccine candidate against Chikungunya, Japanese Encephalitis, Yellow Fever and Zika Virus. Sci Reports 2020 101. 2020;10:1–13.
[4]. Neefjes J, Jongsma MLM, Paul P, Bakke O. Towards a systems understanding of MHC class I and MHC class II antigen presentation. Nat Rev Immunol 2011 1112. 2011;11:823–36.
[5]. Klinman DM, Klaschik S, Sato T, Tross D. CpG oligonucleotides as adjuvants for vaccines targeting infectious diseases. Adv Drug Deliv Rev. 2009;61:248–55.
[6]. Weeratna RD, Millan CLB, McCluskie MJ, Davis HL. CpG ODN can re-direct the Th bias of established Th2 immune responses in adult and young mice. FEMS Immunol Med Microbiol. 2001;32:65–71.
[7]. Vogel FR, Powell MF. A Compendium of Vaccine Adjuvants and Excipients. Pharm Biotechnol. 1995. p. 141–228.


Phase I

Assessing the safety, immunogenicity, and local or systemic reactions in a small set of healthy volunteers. A safe dosage that can be used in humans will be identified.

Phase II

Relying on safety and immunogenicity results from Phase I trials, efficacy and reactions of the vaccine will be determined in a more diverse set of volunteers.

Phase III

Similar to Phase II trials, safety, efficacy, and immunogenicity will be monitored on a much larger scale. The vaccine will be submitted for approval and general production.

Phase IV

Once the vaccine is approved for use, vaccine usage, long-term immunity, and adverse effects will be continuously monitored and investigated on the general population.


Artun Bülbül
Bilkent University

Aslı Gülce Bartan
Bilkent University

Başak Kayaoğlu

Berfu Saraydar
Bilkent University

Bilgehan İbibik
Bilkent University

Bilgi Güngör

Eda Çiftci Dede
Hacettepe University

Emre Mert İpekoğlu

Gamze Aykut
Bilkent University

Hatice Asena Şanlı

İhsan Gürsel
Bilkent University

İlayda Baydemir

İrem Evcili
Bilkent University

İsmail Cem Yılmaz

Mayda Gürsel

Merve Gizer
Hacettepe University

Muzaffer Yıldırım
Bilkent University

Naz Sürücü Yılmaz

Neşe Güvençli

Nilsu Turay
Bilkent University

Petek Korkusuz
Hacettepe University

Sefa Burak Çam
Hacettepe University

Tamer Kahraman
Bilkent University

Tuğçe Bildik
Bilkent University

Tuğçe Canavar Yıldırım
Bilkent University

Yağmur Aydın

Yasemin Özsürekçi
Hacettepe University


Delta Variant in Phase III Clinical Study
VLP-based COVID-19 vaccine to be tested against Delta variant in Phase-3.

VLP Vaccine Phase 2 Vaccinations
Phase 2 vaccinations have been completed, results are now being evaluated.

Volunteers for Phase II Clinical Study
VLP-based COVID-19 vaccine started to be administered to volunteers in Phase-2 stage.

Interview with Prof. Mayda Gürsel
VLP-based domestic COVID-19 vaccine

Volunteers for Phase I Clinical Study
Minister of Industry and Technology, Mustafa Varank, and President of TÜBİTAK, Prof. Hasan Mandal, volunteered for the phase I clinical study.

Last Updated:
03/23/2023 - 23:22