scholarly journals Intranasal HD-Ad vaccine protects the upper and lower respiratory tracts of hACE2 mice against SARS-CoV-2

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Huibi Cao ◽  
Juntao Mai ◽  
Zhichang Zhou ◽  
Zhijie Li ◽  
Rongqi Duan ◽  
...  

Abstract Background The ongoing COVID-19 pandemic has resulted in 185 million recorded cases and over 4 million deaths worldwide. Several COVID-19 vaccines have been approved for emergency use in humans and are being used in many countries. However, all the approved vaccines are administered by intramuscular injection and this may not prevent upper airway infection or viral transmission. Results Here, we describe a novel, intranasally delivered COVID-19 vaccine based on a helper-dependent adenoviral (HD-Ad) vector. The vaccine (HD-Ad_RBD) produces a soluble secreted form of the receptor binding domain (RBD) of the SARS-CoV-2 spike protein and we show it induced robust mucosal and systemic immunity. Moreover, intranasal immunization of K18-hACE2 mice with HD-Ad_RBD using a prime-boost regimen, resulted in complete protection of the upper respiratory tract against SARS-CoV-2 infection. Conclusion Our approaches provide a powerful platform for constructing highly effective vaccines targeting SARS-CoV-2 and its emerging variants.

2021 ◽  
Author(s):  
Huibi Cao ◽  
Juntao Mai ◽  
Zhichang Zhou ◽  
Zhijie Li ◽  
Rongqi Duan ◽  
...  

AbstractThe COVID-19 pandemic has affected more than 120 million people and resulted in over 2.8 million deaths worldwide. Several COVID-19 vaccines have been approved for emergency use in humans and are being used in many countries. However, all of the approved vaccines are administered by intramuscular injection and this may not prevent upper airway infection or viral transmission. Here, we describe intranasal immunization of a COVID-19 vaccine delivered by a novel platform, the helper-dependent adenoviral (HD-Ad) vector. Since HD-Ad vectors are devoid of adenoviral coding sequences, they have a superior safety profile and a large cloning capacity for transgenes. The vaccine (HD-Ad_RBD) codes for the receptor binding domain (RBD) of the SARS-CoV-2 spike protein and intranasal immunization induced robust mucosal and systemic immunity. Moreover, intranasal immunization of K18-hACE2 mice with HD-Ad_RBD using a prime-boost regimen, resulted in complete protection of the upper respiratory tract against SARS-CoV-2 infection. As such, intranasal immunization based on the HD-Ad vector promises to provide a powerful platform for constructing highly effective vaccines targeting SARS-CoV-2 and its emerging variants.


2021 ◽  
Author(s):  
Chrissy Eckstrand ◽  
Tom Baldwin ◽  
Mia Kim Torchetti ◽  
Mary Lea Killian ◽  
Kerry A Rood ◽  
...  

The breadth of animal hosts that are susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and may serve as reservoirs for continued viral transmission are not known entirely. In August 2020, an outbreak of SARS-CoV-2 occurred in multiple mink farms in Utah and was associated with high mink mortality and rapid viral transmission between animals. The outbreak's epidemiology, pathology, molecular characterization, and tissue distribution of virus within infected mink is provided. Infection of mink was likely by reverse zoonosis. Once established, infection spread rapidly between independently housed animals and farms, and caused severe respiratory disease and death. Clinical signs were most notably sudden death, anorexia, and increased respiratory effort. Gross pathology examination revealed severe pulmonary congestion and edema. Microscopically there was pulmonary edema with moderate vasculitis, perivasculitis, and fibrinous interstitial pneumonia. Reverse transcriptase polymerase chain reaction (RT-PCR) of tissues collected at necropsy demonstrated the presence of SARS-CoV-2 viral RNA in multiple organs including nasal turbinates, lung, tracheobronchial lymph node, epithelial surfaces, and others. Whole genome sequencing from multiple mink was consistent with published SARS-CoV-2 genomes with few polymorphisms. The Utah mink SARS-CoV-2 strain fell into Clade GH, which is unique among mink and other animal strains sequenced to date and did not share other spike RBD mutations Y453F and F486L found in mink. Localization of viral RNA by in situ hybridization revealed a more localized infection, particularly of the upper respiratory tract. Mink in the outbreak reported herein had high levels of virus in the upper respiratory tract associated with mink-to-mink transmission in a confined housing environment and were particularly susceptible to disease and death due to SARS-CoV-2 infection.


2000 ◽  
Vol 68 (3) ◽  
pp. 1664-1671 ◽  
Author(s):  
Elena S. Lysenko ◽  
Jane Gould ◽  
Robert Bals ◽  
James M. Wilson ◽  
Jeffrey N. Weiser

ABSTRACT A number of pathogens of the upper respiratory tract express an unusual prokaryotic structure, phosphorylcholine (ChoP), on their cell surface. We tested the hypothesis that ChoP, also found on host membrane lipids in the form of phosphatidylcholine, acts so as to decrease killing by antimicrobial peptides that target differences between bacterial and host membranes. In Haemophilus influenzae, ChoP is a phase-variable structure on the oligosaccharide portion of the lipopolysaccharide (LPS). There was a bactericidal effect of the peptide LL-37/hCAP18 on a nontypeableH. influenzae strain, with an increasing selection for the ChoP+ phase as the concentration of the peptide was raised from 0 to 10 μg/ml. Moreover, constitutive ChoP-expressing mutants of unrelated strains showed up to 1,000-fold-greater survival compared to mutants without ChoP. The effect of ChoP on resistance to killing by LL-37/hCAP18 was dependent on the salt concentration and was observed only when bacteria were grown in the presence of environmental choline, a requirement for the expression of ChoP on the LPS. Further studies established that there is transcription of the LL-37/hCAP18 gene on the epithelial surface of the human nasopharynx in situ and inducible transcription in epithelial cells derived from the upper airway. The presence of highly variable amounts of LL-37/hCAP18 in normal nasal secretions (<1.2 to >80 μg/ml) was demonstrated with an antibody against this peptide. It was concluded that ChoP alters the bacterial cell surface so as mimic host membrane lipids and decrease killing by LL-37/hCAP18, an antimicrobial peptide that may be expressed on the mucosal surface of the nasopharynx in bactericidal concentrations.


Thorax ◽  
2010 ◽  
Vol 65 (2) ◽  
pp. 181-186 ◽  
Author(s):  
R. P. Baughman ◽  
E. E. Lower ◽  
T. Tami

PEDIATRICS ◽  
1980 ◽  
Vol 65 (4) ◽  
pp. 860-860 ◽  
Author(s):  
R. Morrison Hurley ◽  
J. R. Kearns

There have been two reports of children1 and adults2 developing acute pulmonary edema secondary to acute upper airway obstruction. We are reporting a similar case which demonstrates the same association. A 5-year-old girl had a mild upper respiratory tract infection and harsh cough two days prior to admission in April 1975. She awakened suddenly the evening of admission unable to breathe. She improved slightly in the cold outside air en route to hospital, but on arrival she developed acute distress with laryngeal stridor suprasternal and intercostal indrawing.


PEDIATRICS ◽  
1979 ◽  
Vol 63 (2) ◽  
pp. 228-231
Author(s):  
Lawrence Kurlandsky ◽  
Jonathan Y. Lukoff ◽  
William H. Zinkham ◽  
Judith P. Brody ◽  
Richard W. Kessler

The Munchausen syndrome by proxy is a phenomenon in which symptoms of a disease are fabricated by some person other than the patient. This report describes an 8-week-old infant with repetitive bleeding episodes, presumably originating from the upper respiratory tract. Extensive investigations, including angiography, several endoscopies under general anesthesia, and reinfusion of the infant's red cells labeled with 51Cr followed by pulmonary and upper airway scanning, failed to reveal the source of bleeding. Within two weeks after initiation of the 51Cr studies, radioactivity of facial blood from two separate bleeding episodes did not exceed background counts. Soimultaneous examination of the infant's capillary blood, however, showed moderate to marked radioactivity. The Rh subtype of the facial blood was cc, whereas the infant's type was Cc. These findings indicated that the facial blood was factitious in origin. No further "bleeding" occurred after this information was presented to the parents. This case represents an unusual example of the Munchausen syndrome by proxy. Awareness of this entity can prevent potentially harmful investigations. Documenting its occurrence and sharing the information with parents in a nonaccusatory manner may prevent future harm to the patient.


2015 ◽  
Vol 2015 (0) ◽  
pp. _GS41-1_-_GS41-2_
Author(s):  
Hiroki TAKEMOTO ◽  
Masashi YAMAKAWA ◽  
Kenichi MATSUNO

2017 ◽  
Vol 3 (2) ◽  
pp. 313-316 ◽  
Author(s):  
Mathias Scheel ◽  
Andreas Berndt ◽  
Olaf Simanski

AbstractThe obstructive sleep apnoea syndrome (OSAS) is characterized by a collapse of the upper respiratory tract, resulting in a reduction of the blood oxygen- and an increase of the carbon dioxide (CO2) - concentration, which causes repeated sleep disruptions. The gold standard to treat the OSAS is the continuous positive airway pressure (CPAP) therapy. The continuous pressure keeps the upper airway open and prevents the collapse of the upper respiratory tract and the pharynx. Most of the available CPAP-devices cannot maintain the pressure reference [1]. In this work a model predictive control approach is provided. This control approach has the possibility to include the patient’s breathing effort into the calculation of the control variable. Therefore a patient-individualized control strategy can be developed.


1941 ◽  
Vol 74 (3) ◽  
pp. 203-212 ◽  
Author(s):  
John B. Nelson

Fowl pox virus from active skin lesions was established in the upper respiratory tract of normal chickens by nasal instillation and maintained for 12 successive passages. The nasal infection was not communicable by direct contact but did afford protection, for at least 6 weeks, against subsequent development of the virus in the skin. Multiplication of the virus in the nasal passages was only irregularly attended by specific mucosal changes and was not accompanied by the vigorous counter-reaction engendered by the causal agents of roup. The same strain of virus on propagation in embryonated eggs also survived and multiplied in the nasal tract but with somewhat reduced activity, the 34th egg transfer failing to afford complete protection. Nasal instillation in mice was followed only by a reaction in the lung from which the virus was recoverable through the 7th day.


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