A Single-Dose Intranasal ChAd Vaccine Protects Upper and Lower Respiratory Tracts against SARS-CoV-2

Hassan, Ahmed O.; Kafai, Natasha M.; Dmitriev, Igor; Fox, Julie M.; Smith, Brian K.; Harvey, Ian B.; Chen, Rita E.; Winkler, Emma S.; Wessel, Alex W.; Case, James Brett; Kashentseva, Elena A.; McCune, Broc T.; Bailey, Adam L.; Zhao, Haiyan; VanBlargan, Laura A.; Dai, Ya-Nan; Ma, Mingyu; Adams, Lucas J.; Shrihari, Swathi; Danis, Jonathan E.; Gralinski, Lisa E.; Hou, Yixuan J.; Schäfer, Alexandra; Kim, Arthur S.; Keeler, Shamus P.; Weiskopf, Daniela; Baric, Ralph S.; Holtzman, Michael J.; Fremont, Daved H.; Curiel, David T.; Diamond, Michael S.

doi:10.1016/j.cell.2020.08.026

Cited by 514 publications

(622 citation statements)

References 70 publications

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“…To quantify viral load in nasal swabs and lung tissue homogenates, RNA was extracted using RNA isolation kit (Omega). SARS-CoV-2 RNA levels were measured by one-step quantitative reverse transcriptase PCR (qRT-PCR) TaqMan assay as described previously [23]. A SARS- FBS.…”

Section: Methodsmentioning

confidence: 99%

“…Here, we tested the efficacy of a chimpanzee adenovirus (ChAd)-vectored vaccine expressing a prefusion-stabilized version of the S protein of SARS-CoV-2 (ChAd-SARS-CoV-2-S, [23]) in Syrian hamsters following IM or intranasal (IN) delivery. A single dose of the vaccine induced a robust S protein specific antibody response capable of neutralizing SARS-CoV-2, with IN delivery inducing approximately 6-fold higher antibody titers than IM delivery.…”

Section: Introductionmentioning

confidence: 99%

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A single intranasal or intramuscular immunization with chimpanzee adenovirus vectored SARS-CoV-2 vaccine protects against pneumonia in hamsters

Bricker

Hassan

Harastani

et al. 2020

Preprint

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The development of an effective vaccine against SARS-CoV-2, the etiologic agent of COVID-19, is a global priority. Here, we compared the protective capacity of intranasal and intramuscular delivery of a chimpanzee adenovirus-vectored vaccine encoding a pre-fusion stabilized spike protein (ChAd-SARS-CoV-2-S) in Golden Syrian hamsters. While immunization with ChAd-SARS-CoV-2-S induced robust spike protein specific antibodies capable or neutralizing the virus, antibody levels in serum were higher in hamsters immunized by an intranasal compared to intramuscular route. Accordingly, ChAd-SARS-CoV-2-S immunized hamsters were protected against a challenge with a high dose of SARS-CoV-2. After challenge, ChAd-SARS-CoV-2-S-immunized hamsters had less weight loss and showed reductions in viral RNA and infectious virus titer in both nasal swabs and lungs, and reduced pathology and inflammatory gene expression in the lungs, compared to ChAd-Control immunized hamsters. Intranasal immunization with ChAd-SARS-CoV-2-S provided superior protection against SARS-CoV-2 infection and inflammation in the upper respiratory tract. These findings support intranasal administration of the ChAd-SARS-CoV-2-S candidate vaccine to prevent SARS-CoV-2 infection, disease, and possibly transmission.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A single intranasal or intramuscular immunization with chimpanzee adenovirus vectored SARS-CoV-2 vaccine protects against pneumonia in hamsters

Bricker

Hassan

Harastani

et al. 2020

Preprint

Self Cite

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“… 85 Formats involving whole viruses under investigation include live-attenuated virus vaccine, 187 inactivated virus vaccine, 188 , 189 and adenovirus-based vaccines. 190 , 191 Subunit vaccines have also had promising results with some progressing to ongoing clinical studies. 192 Nucleic acid-based vaccines have recently come into the spotlight with both Moderna and Pfizer’s mRNA vaccines showing promising results 193 and progressing rapidly in the development pipeline.…”

Section: Current Therapeutic Paradigm In Pulmonary Host Modulationmentioning

confidence: 99%

Biomaterials-Based Opportunities to Engineer the Pulmonary Host Immune Response in COVID-19

Jarai

Stillman

Bomb

et al. 2020

ACS Biomater. Sci. Eng.

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The COVID-19 pandemic caused by the global spread of the SARS-CoV-2 virus has led to a staggering number of deaths worldwide and significantly increased burden on healthcare as nations scramble to find mitigation strategies. While significant progress has been made in COVID-19 diagnostics and therapeutics, effective prevention and treatment options remain scarce. Because of the potential for the SARS-CoV-2 infections to cause systemic inflammation and multiple organ failure, it is imperative for the scientific community to evaluate therapeutic options aimed at modulating the causative host immune responses to prevent subsequent systemic complications. Harnessing decades of expertise in the use of natural and synthetic materials for biomedical applications, the biomaterials community has the potential to play an especially instrumental role in developing new strategies or repurposing existing tools to prevent or treat complications resulting from the COVID-19 pathology. Leveraging microparticle- and nanoparticle-based technology, especially in pulmonary delivery, biomaterials have demonstrated the ability to effectively modulate inflammation and may be well-suited for resolving SARS-CoV-2-induced effects. Here, we provide an overview of the SARS-CoV-2 virus infection and highlight current understanding of the host’s pulmonary immune response and its contributions to disease severity and systemic inflammation. Comparing to frontline COVID-19 therapeutic options, we highlight the most significant untapped opportunities in immune engineering of the host response using biomaterials and particle technology, which have the potential to improve outcomes for COVID-19 patients, and identify areas needed for future investigations. We hope that this work will prompt preclinical and clinical investigations of promising biomaterials-based treatments to introduce new options for COVID-19 patients.

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“…One 2 is based on a weakened livestock virus. The other 3 is based on a chimpanzee adenovirus, like the Oxford-AstraZeneca effort.…”

Section: Dozens Of Candidatesmentioning

confidence: 99%

The underdog coronavirus vaccines that the world will need if front runners stumble

Callaway¹

2020

Nature

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clinical-trial holds in future. The transparency bar should be set much higher than this latest example, says Kieny. "When, ultimately, a vaccine will be made available, public trust will be paramount to ensure public-health impact. And trust needs transparency." Leading vaccine The vaccine, AZD1222, is one of the leading candidates being developed to protect against the virus that causes COVID-19, and one of a handful of immunizations in the final stages of clinical testing. The pause in global trials sent a shudder around the world. Such a quick resumption of the trials was the most likely outcome, says Paul Griffin, an infectious-diseases researcher at the University of Queensland in Brisbane, Australia. In large trials, adverse medical events in volunteers are common, and trial holds are designed to ensure that such events are investigated and volunteers are protected, he says. But, most often, it is later decided that the event was probably not related to participation in the trial and does not pose a safety concern to the rest of the volunteers, says Griffin. That seems to be what has occurred in this case, he says. It can be difficult to pin down the cause of adverse events, says Jonathan Kimmelman, a bioethicist who studies clinical trials at McGill University in Montreal, Canada. "Often, the best you can do is say that there is a possible link, and then proceed with collecting more data and monitoring outcomes," he says. The University of Oxford said in a press release on 12 September that the pause, which applied to all trials of the vaccine, was necessary "to allow the review of safety data by an independent safety review committee, and the national regulators". "The independent review process has concluded and following the recommendations of both the independent safety review committee and the UK regulator, the MHRA [Medicines and Healthcare products Regulatory Agency], the trials will recommence in the UK," the statement reads. The university also said that it cannot disclose medical information about the participant's illness for reasons of confidentiality.

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A Single-Dose Intranasal ChAd Vaccine Protects Upper and Lower Respiratory Tracts against SARS-CoV-2

Cited by 514 publications

References 70 publications

A single intranasal or intramuscular immunization with chimpanzee adenovirus vectored SARS-CoV-2 vaccine protects against pneumonia in hamsters

A single intranasal or intramuscular immunization with chimpanzee adenovirus vectored SARS-CoV-2 vaccine protects against pneumonia in hamsters

Biomaterials-Based Opportunities to Engineer the Pulmonary Host Immune Response in COVID-19

The underdog coronavirus vaccines that the world will need if front runners stumble

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