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Master Thesis

Anti-SARS-CoV-2 vaccine strategies: immunogenicity evaluation of two vaccine candidates

Abstract : The work presented in this thesis includes a bibliographic study of the various SARS-CoV-2 vaccine strategies available, followed by the evaluation of the immunogenicity of two vaccine candidates developed by two teams at the Structural Biology Institute of Grenoble. The two approaches are based on the use of the SARS-CoV-2 spike as an antigen for the induction of protective neutralising antibodies. The vaccine candidate shares the common feature of using platforms that lead to the multimerisation of protein antigens, a feature known to induce a stronger humoral response. The first vaccine candidate named "ADDomer", developed by the team of Dr Fender uses the self-assembly capabilities of adenovirus type 3 penton protein subunits to create viral pseudoparticles (VLPs). The VLPs are then decorated with recombinant receptor binding domain (RBD) of the SARS-CoV-2 spike. Immunogenicity of the vaccine candidate was assessed by immunisation of mice. Measurement of anti-RBD antibody response by Enzyme Linked ImmunoSorbent Assay (ELISA) showed high titers, appearing as early as two weeks after the first injection. In addition to the ELISA tests, neutralisation assays demonstrated the ability of the vaccine candidate to induce neutralising antibodies, also at high levels. As adenovirus type 3 is highly prevalent in certain populations, the impact of the existence of pre-immunity was studied by pre-immunising a group of mice with ADDomer alone, prior to injection of the ADDomer-RBD. Antibody responses in this group were earlier and greater than in groups without pre-immunity, suggesting a possible advantage of pre-immunisation, in contrast to what has been described in vaccine strategies based on human adenoviral vectors. The second vaccine candidate developed by the team of Professor Weissenhorn is based on the use of liposomal particles decorated with SARS-CoV-2 stabilized trimeric spikes. Immunisation of macaques demonstrated its good tolerance and high immunogenicity. Anti-RBD and anti-spike antibodies were detected as early as two weeks after the first immunisation and reached high levels following the second and third immunisations. Similarly, serum from vaccinated animals showed strong neutralising activity against SARS-CoV-2. To evaluate the protection conferred by the vaccine, the vaccinated animals were subjected to a nasal aerosol of SARS-CoV-2, compared to a control group of unvaccinated macaques. No viral load or lung lesions were detected in the vaccinated animals, indicating a complete absence of infection and sterilizing immunity. On the contrary, the control animals all developed the disease. In conclusion, the two vaccine approaches evaluated allowed the efficient induction of anti-spike antibodies with a strong neutralising activity against SARS-CoV-2. The liposome-spike approach provided complete protection, most likely preventing transmission, a property that should be confirmed in future larger studies. The ADDomer approach is an interesting vaccine platform because of its adaptability and could be used to combat future pathogens.
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Master Thesis
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Submitted on : Tuesday, January 25, 2022 - 2:41:32 PM
Last modification on : Wednesday, February 2, 2022 - 3:39:26 AM
Long-term archiving on: : Tuesday, April 26, 2022 - 6:55:09 PM


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  • HAL Id : dumas-03542629, version 1


Axelle Amen. Anti-SARS-CoV-2 vaccine strategies: immunogenicity evaluation of two vaccine candidates. Pharmaceutical sciences. 2022. ⟨dumas-03542629⟩



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