Comparative anatomy of the mitral valve in four species (human, ovine, porcine and canine): A pre-clinical perspective.

This study aimed to provide comparative anatomical data on the mitral valve and to substantiate the choice between large species for pre-clinical testing of cardiac devices. Different anatomical parameters of the anterior and posterior leaflets, chordae and papillary muscles were measured to characterize the anatomy of the mitral valve in 10 individuals for each four species. Ratios were calculated and used to circumvent the interspecies variations of body and heart size and weight. The results underline many relevant anatomical similarities and differences between man and the three animal species. We confirm that the porcine species is a better model based on anatomical measurements. But many parameters should be considered depending on the shape, size and purpose of the device. The mitral and aortic valve are closer than in man leading to potential damage of the aortic valve by a mitral device. The ovine mitral annulus is more flattened and would sustain more mechanical forces on a round-shaped stent. The anterior and posterior leaflets have comparable height in the animal species leading to more space for implantation. The porcine valve has more chordae allowing less space around the valve for a transcatheter stent. Our observations introduce new comparative data in the perspective of the choice of a large animal model for pre-clinical testing of mitral devices. They are very helpful for all cardiologists, surgeons or engineers who need to understand the reasons for success or failure of a device and to have key elements of discussion.

Intranasal Immunization with a Lentiviral Vector Coding for SARS-CoV-2 Spike Protein Confers Vigorous Protection in Pre-Clinical Animal Models

To develop a vaccine candidate against COVID-19, we generated a Lentiviral Vector (LV), eliciting neutralizing antibodies against the Spike glycoprotein of SARS-CoV-2. Systemic vaccination by this vector in mice, in which the expression of the SARS-CoV-2 receptor hACE2 has been induced by transduction of respiratory tract cells by an adenoviral vector, conferred only partial protection, despite an intense serum neutralizing activity. However, targeting the immune response to the respiratory tract through an intranasal boost with this LV resulted in > 3 log10 decrease in the lung viral loads and avoided local inflammation. Moreover, both integrative and non-integrative LV platforms displayed a strong vaccine efficacy and inhibited lung deleterious injury in golden hamsters, which are naturally permissive to SARS-CoV-2 replication and restitute the human COVID-19 physiopathology. Our results provide evidence of marked prophylactic effects of the LV-based vaccination against SARS-CoV-2 and designate the intranasal immunization as a powerful approach against COVID-19. HighlightsA lentiviral vector encoding for Spike predicts a promising COVID-19 vaccine Targeting the immune response to the upper respiratory tract is key to protection Intranasal vaccination induces protective mucosal immunity against SARS-CoV-2 Lung anti-Spike IgA responses correlate with protection and reduced inflammation