Développement de vaccins sous-unitaires contre le métapneumovirus humain
|Abstract:||The human metapneumovirus has been first isolated in 2001 despite its circulation in the human population for more than 70 years. HMPV is the third leading cause of children hospitalisations associated with acute respiratory tract infections. Complications occur commonly in young children, the elderly and the immunocompromised. To this day, no vaccine has been licensed for use against hMPV. In recent years, the F protein, considered the most immunodominant antigen, has been the target of many pre-clinical vaccine trials. The discovery, for RSV, that a prefusion bound F protein is more immunogenic than post-fusion has encouraged new vaccination approaches. Based on this discovery, the aim of this project is the development of a prefusion bound F-hMPV subunit vaccine and testing its potency to protect the BALB/C model. Following challenge, no significant difference between potentially prefusion bound proteins and wild type protein was observed. Immunisation trials revealed the necessity of adding an adjuvant, alum in this case, to elicit an immune response in mice. Neutralizing antibodies were observed with F-hMPV vaccines containing the alum adjuvant. Post-immunisation challenge trials revealed reduction of lung viral replication below detection levels and persisting inflammation. Weight loss was not affected by vaccination, but animals immunised with adjuvanted F-hMPV proteins exhibited better physical condition and no signs of disease such as diminished activity and ruffed fur. F-hMPV vaccines without alum exhibited some characteristics of enhanced disease (no neutralizing antibodies; affected physical condition) and require further analysis. Enhanced disease was not observed in the F-hMPV adjuvanted groups despite higher Th2/Th1 ratios with adjuvanted proteins . None of the vaccines tested were able to fully protect the mouse model upon challenge. Vaccines developed in this study will be useful in future trials and could be tested with other adjuvants or vaccination strategies.|
|Document Type:||Mémoire de maîtrise|
|Open Access Date:||28 November 2018|
|Collection:||Thèses et mémoires|
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