Intranasal ChAdOx1 nCoV-19/AZD1222 vaccination reduces viral shedding after SARS-CoV-2 D614G challenge in preclinical models

Neeltje van Doremalen(National Institutes of Health), Jyothi N. Purushotham(National Institutes of Health), Jonathan E. Schulz(National Institutes of Health), Myndi G. Holbrook(National Institutes of Health), Trenton Bushmaker(National Institutes of Health), Aaron Carmody(Rocky Mountain Research (United States)), Julia R. Port(National Institutes of Health), Claude Kwe Yinda(National Institutes of Health), Atsushi Okumura(National Institutes of Health), Greg Saturday(National Institutes of Health), Fatima Amanat(Icahn School of Medicine at Mount Sinai), Florian Krammer(Icahn School of Medicine at Mount Sinai), Patrick W. Hanley(National Institutes of Health), Brian J. Smith(National Institutes of Health), Jamie Lovaglio(National Institutes of Health), Sarah L. Anzick(Rocky Mountain Research (United States)), Kent Barbian(Rocky Mountain Research (United States)), Craig Martens(Rocky Mountain Research (United States)), Sarah C. Gilbert(University of Oxford), Teresa Lambe(University of Oxford), Vincent J. Munster(National Institutes of Health)
Science Translational Medicine
July 27, 2021
Cited by 266Open Access
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Abstract

ChAdOx1 nCoV-19/AZD1222 is an approved adenovirus-based vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) currently being deployed globally. Previous studies in rhesus macaques revealed that intramuscular vaccination with ChAdOx1 nCoV-19/AZD1222 provided protection against pneumonia but did not reduce shedding of SARS-CoV-2 from the upper respiratory tract. Here, we investigated whether intranasally administered ChAdOx1 nCoV-19 reduces detection of virus in nasal swabs after challenging vaccinated macaques and hamsters with SARS-CoV-2 carrying a D614G mutation in the spike protein. Viral loads in swabs obtained from intranasally vaccinated hamsters were decreased compared to control hamsters, and no viral RNA or infectious virus was found in lung tissue after a direct challenge or after direct contact with infected hamsters. Intranasal vaccination of rhesus macaques resulted in reduced virus concentrations in nasal swabs and a reduction in viral loads in bronchoalveolar lavage and lower respiratory tract tissue. Intranasal vaccination with ChAdOx1 nCoV-19/AZD1222 reduced virus concentrations in nasal swabs in two different SARS-CoV-2 animal models, warranting further investigation as a potential vaccination route for COVID-19 vaccines.


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