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1.
Cell Rep Med ; 3(2): 100520, 2022 02 15.
Article in English | MEDLINE | ID: covidwho-1633496

ABSTRACT

Effective vaccines are essential for the control of the coronavirus disease 2019 (COVID-19) pandemic. Currently developed vaccines inducing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S)-antigen-specific neutralizing antibodies (NAbs) are effective, but the appearance of NAb-resistant S variant viruses is of great concern. A vaccine inducing S-independent or NAb-independent SARS-CoV-2 control may contribute to containment of these variants. Here, we investigate the efficacy of an intranasal vaccine expressing viral non-S antigens against intranasal SARS-CoV-2 challenge in cynomolgus macaques. Seven vaccinated macaques exhibit significantly reduced viral load in nasopharyngeal swabs on day 2 post-challenge compared with nine unvaccinated controls. The viral control in the absence of SARS-CoV-2-specific NAbs is significantly correlated with vaccine-induced, viral-antigen-specific CD8+ T cell responses. Our results indicate that CD8+ T cell induction by intranasal vaccination can result in NAb-independent control of SARS-CoV-2 infection, highlighting a potential of vaccine-induced CD8+ T cell responses to contribute to COVID-19 containment.


Subject(s)
Administration, Intranasal/methods , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , CD8-Positive T-Lymphocytes/immunology , COVID-19 Vaccines/administration & dosage , COVID-19/immunology , COVID-19/prevention & control , SARS-CoV-2/immunology , Vaccination/methods , Animals , COVID-19/epidemiology , COVID-19/virology , COVID-19 Vaccines/immunology , Chlorocebus aethiops , Coronavirus Envelope Proteins/immunology , Coronavirus M Proteins/immunology , Coronavirus Nucleocapsid Proteins/immunology , Disease Models, Animal , Female , Macaca fascicularis , Male , Pandemics/prevention & control , Phosphoproteins/immunology , Spike Glycoprotein, Coronavirus/immunology , Treatment Outcome , Vero Cells , Viral Load
3.
Cell Rep ; 36(4): 109452, 2021 07 27.
Article in English | MEDLINE | ID: covidwho-1306891

ABSTRACT

SARS-CoV-2 variants that attenuate antibody neutralization could jeopardize vaccine efficacy. We recently reported the protective activity of an intranasally administered spike protein-based chimpanzee adenovirus-vectored vaccine (ChAd-SARS-CoV-2-S) in animals, which has advanced to human trials. Here, we assessed its durability, dose response, and cross-protective activity in mice. A single intranasal dose of ChAd-SARS-CoV-2-S induced durably high neutralizing and Fc effector antibody responses in serum and S-specific IgG and IgA secreting long-lived plasma cells in the bone marrow. Protection against a historical SARS-CoV-2 strain was observed across a 100-fold vaccine dose range and over a 200-day period. At 6 weeks or 9 months after vaccination, serum antibodies neutralized SARS-CoV-2 strains with B.1.351, B.1.1.28, and B.1.617.1 spike proteins and conferred almost complete protection in the upper and lower respiratory tracts after challenge with variant viruses. Thus, in mice, intranasal immunization with ChAd-SARS-CoV-2-S provides durable protection against historical and emerging SARS-CoV-2 strains.


Subject(s)
Antibodies, Neutralizing/pharmacology , SARS-CoV-2/pathogenicity , Spike Glycoprotein, Coronavirus/immunology , Viral Vaccines/pharmacology , Administration, Intranasal/methods , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Antibodies, Viral/pharmacology , Mice , Vaccination/methods , Viral Vaccines/immunology
4.
Otolaryngol Head Neck Surg ; 163(4): 682-694, 2020 10.
Article in English | MEDLINE | ID: covidwho-999410

ABSTRACT

OBJECTIVE: To provide a state of the art review of intranasal antiviral drug delivery and to discuss current applications, adverse reactions, and future considerations in the management of coronavirus disease 2019 (COVID-19). DATA SOURCES: PubMed, Embase, and Clinicaltrials.gov search engines. REVIEW METHODS: A structured search of the current literature was performed of dates up to and including April 2020. Search terms were queried as related to topics of antiviral agents and intranasal applications. A series of video conferences was convened among experts in otolaryngology, infectious diseases, public health, pharmacology, and virology to review the literature and discuss relevant findings. CONCLUSIONS: Intranasal drug delivery for antiviral agents has been studied for many years. Several agents have broad-spectrum antiviral activity, but they still require human safety and efficacy trials prior to implementation. Intranasal drug delivery has potential relevance for future clinical trials in the settings of disease spread prevention and treatment of SARS-CoV-2 and other viral diseases. IMPLICATIONS FOR PRACTICE: Intranasal drug delivery represents an important area of research for COVID-19 and other viral diseases. The consideration of any potential adverse reactions is paramount.


Subject(s)
Antiviral Agents/administration & dosage , Betacoronavirus , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Administration, Intranasal/methods , COVID-19 , Coronavirus Infections/epidemiology , Drug Delivery Systems , Humans , Pandemics , Pneumonia, Viral/epidemiology , SARS-CoV-2
5.
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
7.
Hum Vaccin Immunother ; 16(12): 2921-2931, 2020 12 01.
Article in English | MEDLINE | ID: covidwho-759862

ABSTRACT

The sudden emergence of a highly transmissible and pathogenic coronavirus SARS-CoV-2 in December 2019 from China and its rapid global spread has posed an international health emergency. The rapid development of an effective vaccine is imperative to control the spread of SARS-CoV-2. A number of concurrent efforts to find an effective therapeutic agent or vaccine for COVID-19 (coronavirus disease 2019) are being undertaken globally. Oral and nasal mucosal surfaces serve as the primary portal of entry for pathogens like coronaviruses in the human body. As evidenced by studies on similar coronaviruses (SARS-CoV and MERS-CoV), mucosal vaccination can provide a safe and effective means for the induction of long-lasting systemic and mucosal immunity to confer protection against SARS-CoV-2. This article summarizes the approaches to an effective mucosal vaccine formulation which can be a rewarding approach to combat the unprecedented threat posed by this emerging global pandemic.


Subject(s)
COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/immunology , COVID-19/immunology , COVID-19/prevention & control , Nasal Mucosa/immunology , SARS-CoV-2/immunology , Administration, Intranasal/methods , Animals , COVID-19/epidemiology , Humans , Nasal Mucosa/drug effects , Protein Structure, Secondary , Protein Structure, Tertiary , SARS-CoV-2/chemistry , SARS-CoV-2/drug effects
8.
Sci Rep ; 10(1): 10568, 2020 06 29.
Article in English | MEDLINE | ID: covidwho-618682

ABSTRACT

Topical intra-nasal sprays are amongst the most commonly prescribed therapeutic options for sinonasal diseases in humans. However, inconsistency and ambiguity in instructions show a lack of definitive knowledge on best spray use techniques. In this study, we have identified a new usage strategy for nasal sprays available over-the-counter, that registers an average 8-fold improvement in topical delivery of drugs at diseased sites, when compared to prevalent spray techniques. The protocol involves re-orienting the spray axis to harness inertial motion of particulates and has been developed using computational fluid dynamics simulations of respiratory airflow and droplet transport in medical imaging-based digital models. Simulated dose in representative models is validated through in vitro spray measurements in 3D-printed anatomic replicas using the gamma scintigraphy technique. This work breaks new ground in proposing an alternative user-friendly strategy that can significantly enhance topical delivery inside human nose. While these findings can eventually translate into personalized spray usage instructions and hence merit a change in nasal standard-of-care, this study also demonstrates how relatively simple engineering analysis tools can revolutionize everyday healthcare. Finally, with respiratory mucosa as the initial coronavirus infection site, our findings are relevant to intra-nasal vaccines that are in-development, to mitigate the COVID-19 pandemic.


Subject(s)
Administration, Inhalation , Administration, Intranasal/methods , Betacoronavirus , Coronavirus Infections/prevention & control , Drug Delivery Systems/methods , Nasal Sprays , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , COVID-19 , Computer Simulation , Coronavirus Infections/virology , Humans , Hydrodynamics , Nasal Cavity/anatomy & histology , Nasal Mucosa/drug effects , Nasal Mucosa/virology , Nebulizers and Vaporizers , Paranasal Sinuses/drug effects , Paranasal Sinuses/virology , Pneumonia, Viral/virology , SARS-CoV-2 , Viral Vaccines/administration & dosage
9.
ACS Chem Neurosci ; 11(11): 1523-1524, 2020 06 03.
Article in English | MEDLINE | ID: covidwho-324232

ABSTRACT

There is mounting evidence of the central nervous system manifestations associated with COVID-19, particularly in severe cases. Up to 25% of COVID-19 cases exhibit neurological manifestations associated with COVID-19. In view of the devastating nature of the disease due to severe acute respiratory syndrome coronavirus 2, here we debate intranasal drug delivery, in addition to intravenous delivery, as a therapeutic strategy in the management of COVID-19 cases with central nervous system involvement.


Subject(s)
Administration, Intranasal/methods , Central Nervous System Viral Diseases/drug therapy , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Administration, Intravenous , COVID-19 , Humans , Pandemics
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