Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 4 de 4
Filter
1.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-314575

ABSTRACT

COVID-19 vaccines already in use or in clinical development may have safety concerns, limited immunogenicity in high-risk groups or reduced efficacy against emerging SARS-CoV-2 variants. In addition, although the neurotropism of SARS-CoV-2 is well established, the vaccine strategies currently developed have not taken into account the protection of the central nervous system. Here, we generated a transgenic mouse strain expressing the human Angiotensin Converting Enzyme 2, with unprecedented brain as well as lung permissibility to SARS-CoV-2 replication. Using this stringent transgenic model, we demonstrated that a non-integrative lentiviral vector, encoding for the spike glycoprotein of the ancestral Wuhan SARS-CoV-2, used in intramuscular prime and intranasal boost elicits sterilizing protection of lung and brain against both the Wuhan and the most genetically distant Manaus P.1 SARS-CoV-2 variants. Beyond the induction of strong neutralizing antibodies, the mechanism underlying this broad protection spectrum involves a robust protective spike-specific CD8+ T-cell immunity, unaffected by the recent mutations accumulated in the emerging SARS-CoV-2 variants.

2.
EMBO Mol Med ; 13(12): e14459, 2021 12 07.
Article in English | MEDLINE | ID: covidwho-1468845

ABSTRACT

COVID-19 vaccines already in use or in clinical development may have reduced efficacy against emerging SARS-CoV-2 variants. In addition, although the neurotropism of SARS-CoV-2 is well established, the vaccine strategies currently developed have not taken into account protection of the central nervous system. Here, we generated a transgenic mouse strain expressing the human angiotensin-converting enzyme 2, and displaying unprecedented brain permissiveness to SARS-CoV-2 replication, in addition to high permissiveness levels in the lung. Using this stringent transgenic model, we demonstrated that a non-integrative lentiviral vector, encoding for the spike glycoprotein of the ancestral SARS-CoV-2, used in intramuscular prime and intranasal boost elicits sterilizing protection of lung and brain against both the ancestral virus, and the Gamma (P.1) variant of concern, which carries multiple vaccine escape mutations. Beyond induction of strong neutralizing antibodies, the mechanism underlying this broad protection spectrum involves a robust protective T-cell immunity, unaffected by the recent mutations accumulated in the emerging SARS-CoV-2 variants.


Subject(s)
COVID-19 , SARS-CoV-2 , Animals , Antibodies, Neutralizing , Antibodies, Viral , Brain/metabolism , COVID-19 Vaccines , Humans , Mice , Mice, Transgenic , Spike Glycoprotein, Coronavirus/metabolism
3.
Eur J Immunol ; 51(1): 180-190, 2021 01.
Article in English | MEDLINE | ID: covidwho-1023283

ABSTRACT

Although the COVID-19 pandemic peaked in March/April 2020 in France, the prevalence of infection is barely known. Using high-throughput methods, we assessed herein the serological response against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) of 1847 participants working in three sites of an institution in Paris conurbation. In May-July 2020, 11% (95% confidence interval [CI]: 9.7-12.6) of serums were positive for IgG against the SARS-CoV-2 N and S proteins, and 9.5% (95% CI: 8.2-11.0) were neutralizer in pseudo-typed virus assays. The prevalence of seroconversion was 11.6% (95% CI: 10.2-13.2) when considering positivity in at least one assay. In 5% of RT-qPCR positive individuals, no systemic IgGs were detected. Among immune individuals, 21% had been asymptomatic. Anosmia (loss of smell) and ageusia (loss of taste) occurred in 52% of the IgG-positive individuals and in 3% of the negative ones. In contrast, 30% of the anosmia-ageusia cases were seronegative, suggesting that the true prevalence of infection may have reached 16.6%. In sera obtained 4-8 weeks after the first sampling, anti-N and anti-S IgG titers and neutralization activity in pseudo-virus assay declined by 31%, 17%, and 53%, resulting thus in half-life of 35, 87, and 28 days, respectively. The population studied is representative of active workers in Paris. The short lifespan of the serological systemic responses suggests an underestimation of the true prevalence of infection.


Subject(s)
Antibodies, Viral/blood , COVID-19/blood , COVID-19/immunology , Adult , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/epidemiology , Female , Humans , Immunoglobulin G/blood , Immunoglobulin G/immunology , Male , Pandemics , Paris/epidemiology , Seroepidemiologic Studies , Time Factors
4.
Cell Host Microbe ; 29(2): 236-249.e6, 2021 02 10.
Article in English | MEDLINE | ID: covidwho-978240

ABSTRACT

To develop a vaccine candidate against coronavirus disease 2019 (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, confers only partial protection despite high levels of serum neutralizing activity. However, eliciting an immune response in the respiratory tract through an intranasal boost results in a >3 log10 decrease in the lung viral loads and reduces local inflammation. Moreover, both integrative and non-integrative LV platforms display strong vaccine efficacy and inhibit lung deleterious injury in golden hamsters, which are naturally permissive to SARS-CoV-2 replication and closely mirror human COVID-19 physiopathology. Our results provide evidence of marked prophylactic effects of LV-based vaccination against SARS-CoV-2 and designate intranasal immunization as a powerful approach against COVID-19.


Subject(s)
Administration, Intranasal/methods , COVID-19 Vaccines/administration & dosage , COVID-19/immunology , COVID-19/prevention & control , SARS-CoV-2/immunology , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19 Vaccines/immunology , Cricetinae , Female , Genetic Vectors , Immunity, Mucosal , Immunization, Secondary , Immunoglobulin A/immunology , Lentivirus/genetics , Lentivirus/immunology , Male , Mice , Models, Animal , Respiratory System/immunology , Spike Glycoprotein, Coronavirus/immunology , Viral Load
SELECTION OF CITATIONS
SEARCH DETAIL