This article is a Preprint
Preprints are preliminary research reports that have not been certified by peer review. They should not be relied on to guide clinical practice or health-related behavior and should not be reported in news media as established information.
Preprints posted online allow authors to receive rapid feedback and the entire scientific community can appraise the work for themselves and respond appropriately. Those comments are posted alongside the preprints for anyone to read them and serve as a post publication assessment.
Intranasal Immunization with a Lentiviral Vector Coding for SARS-CoV-2 Spike Protein Confers Vigorous Protection in Pre-Clinical Animal Models (preprint)
biorxiv; 2020.
Preprint
in English
| bioRxiv | ID: ppzbmed-10.1101.2020.07.21.214049
ABSTRACT
We developed a potent vaccination strategy, based on lentiviral vector (LV), capable of inducing neutralizing antibodies specific to the Spike glycoprotein (S) of SARS-CoV-2, the etiologic agent of CoronaVirus Disease 2019 (COVID-19). Among several LV encoding distinct variants of S, a single one encoding the full-length, membrane anchored S (LVSFL) triggered high antibody titers in mice, with neutralization activities comparable to patients recovered from COVID-19. LVSFL systemic vaccination in mice, in which the expression of the CoV2 receptor hACE2 was induced by transduction of the respiratory tract cells by an adenoviral type 5 (Ad5) vector, despite an intense serum neutralizing activity, only {approx}1 log10 reduction of lung viral loads was observed after SARS-CoV2 challenge. We thus explored the strategy of targeting the immune response to the upper respiratory tract through an intranasal boost administration. Even though, after a prime and target regimen, the systemic neutralizing activity did not increase substantially, {approx}5 log10 decrease in lung viral loads was achieved, with the loads in some animals under the limit of detection of a highly sensitive RT-PCR assay. The conferred protection also avoided largely pulmonary inflammation. We confirmed the vaccine efficacy and inhibition of lung inflammation using both integrative and non-integrative LV platforms in golden hamsters, naturally permissive to SARS-CoV2 replication and restituting human COVID-19 physiopathology. Our results provide the proof-of-principle evidence of marked prophylactic effects of an LV-based vaccination strategy against SARS-CoV-2 in two pre-clinical animal models and designate the intranasal LVSFL-based immunization as a vigorous and promising vaccine approach against COVID-19.
Full text:
Available
Collection:
Preprints
Database:
bioRxiv
Language:
English
Year:
2020
Document Type:
Preprint
Similar
MEDLINE
...
LILACS
LIS