The intranasal lentiviral vaccine candidate (Lenti-S) protects brain and lung in a pre-clinical animal model

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The SARS-CoV-2 virus, responsible for the COVID-19 pandemic, primarily targets the respiratory tract, but its ability to infect cells of the nervous system has also been largely reported. Indeed, the expression of the receptor of this virus, the Angiotensin Converting Enzyme 2 (ACE2), by neuronal and glial cells makes the brain susceptible to SARS-CoV-2. Moreover, neurological manifestations are present in the majority of hospitalized COVID-19 patients. The development of new COVID-19 vaccine strategies, complementary to those currently implemented, should therefore contribute to the protection of the central nervous system against SARS-CoV-2. To this end, researchers from the Institut Pasteur-TheraVectys Joint Laboratory have demonstrated, in a preclinical animal model, the ability of an intranasal lentiviral vaccine candidate (Lenti-S) to protect not only the lungs but also the brain against the Gamma variant of SARS-CoV-2. These results were published in the EMBO Molecular Medicine journal on October 15, 2021.


COVID-19 is a viral infectious disease whose main symptoms are respiratory. However, neurological manifestations affect many COVID-19 patients. These symptoms may include loss of taste and smell, headache, syncope, but also other more serious conditions such as acute encephalopathy, stroke, epilepsy, meningitis and coma. These various manifestations, whose pathophysiological mechanisms are not yet fully understood, must be taken into account in the vaccine strategies currently in development.

In this context, researchers from the Institut Pasteur-Theravectys Joint Laboratory, headed by Pierre Charneau, have previously developed and established, in preclinical experiments, the efficacy of a lentiviral vector (LV)1 when used for primary vaccination by the muscular route, followed by a boost by the nasal route. This vaccine candidate not only induces in animals long lasting immunity based on neutralizing antibodies but also a strong durable cellular immunity linked to T-cells.

In a new study, researchers from the Institut Pasteur-Theravectys Joint Laboratory have demonstrated, in an animal model2, the ability of the Lenti-S vaccine candidate to induce protection not only of the lungs but also of the central nervous system against SARS-CoV-2 infection. In all animals immunized with the vaccine candidate, viral replication is absent or largely reduced in the brain. Immunization also eliminates the infection-mediated inflammatory phenomena in the brain. The researchers established that the booster injection of Lenti-S by nasal route is necessary in the protection of the brain.

"Intranasal vaccination allows immune defenses to be directed straight into the upper respiratory tract and therefore act immediately at the site of entry of the virus into the body. The protective capacity of the respiratory and nervous systems of Lenti-S extends with the same efficacy to the Gamma variant of SARS-CoV-2 as to the ancestral strain" explains Laleh Majlessi, director of research at the Institut Pasteur-TheraVectys Joint Laboratory, and co-last author of this study.

Beyond the induction of potent neutralizing antibodies, the mechanism responsible for this broad spectrum of protection involves protective immunity based on T cells, whose efficacy remains intact against the Gamma variant of the SARS-CoV-2, despite accumulated mutations in their Spike protein. These data must now be confirmed in human clinical trials.


1. The lentiviral vector is devoid of all viral genes in order to be harmless to humans and produces the Spike protein. This protein, which forms spicules around the virus, is the key to entry of the virus into human cells.
2.​ In the animal model used in this study, expression of the human SARS-CoV-2 receptor (human ACE2) has been artificially induced in the organs including the brain to mimic the neurological effects of COVID-19.


Source

Brain Cross-Protection against SARS-CoV-2 Variants by a Lentiviral Vaccine in New Transgenic Mice, EMBO Molecular Medicine, October 15th, 2021

Min-Wen Ku1, Pierre Authié1, Maryline Bourgine1, François Anna1, Amandine Noirat1, Fanny Moncoq1, Benjamin Vesin1, Fabien Nevo1, Jodie Lopez1, Philippe Souque1, Catherine Blanc1, Ingrid Fert1, Sébastien Chardenoux2, llta Lafosse2, Delphine Cussigh2, David Hardy3, Kirill Nemirov1, Françoise Guinet4, Francina Langa Vives2, Laleh Majlessi1, and Pierre Charneau1

1 Institut Pasteur-TheraVectys Joint Lab, Virology Department, 28 rue du Dr. Roux, Paris F-75015, France
2 Plate-Forme Centre d'Ingénierie Génétique Murine CIGM, Institut Pasteur
3 Experimental Neuropatholgy Unit, Institut Pasteur, 28 rue du Dr. Roux, Paris F-75015, France
4 Lymphocytes and Immunity Unit, Immunology Department, Institut Pasteur

 

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