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Intranasal vaccination with ChAdOx1 nCoV-19 results in reduced nasal shedding and lack of lower respiratory tract infection in SARS-CoV-2 hamsters and rhesus macaques

Neeltje van Doremalen1, Jyothi Purushotham1,2, Sarah Gilbert2, Teresa Lambe2, Craig Martens3, Vincent J. Munster1*

1.Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.  

2.The Jenner Institute, University of Oxford, Oxford, UK.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019 and is responsible for the coronavirus disease 2019 (COVID-19) pandemic. Vaccines are an essential countermeasure and are urgently needed to control the pandemic. Previously we showed that intramuscular vaccination with the adenovirus-vector-based vaccine ChAdOx1 nCoV-19, which encodes the spike protein of SARS-CoV-2, induced a balanced humoral and cellular immune response in rhesus macaques. We observed a significantly reduced viral load in the bronchoalveolar lavage fluid and lower respiratory tract tissue and no pneumonia in vaccinated rhesus macaques that were challenged with SARS-CoV-2 compared with control animals However, there was no difference in nasal shedding between vaccinated and control SARS-CoV-2-infected macaques. Here we explore the potential for intranasal administered ChAdOx1 nCoV-19 to protect against pneumonia and nasal shedding. We vaccinated Syrian golden hamsters with ChAdOx1 nCoV-19 via the intranasal (IN) and intramuscular (IM) route. Direct challenge resulted in nasal shedding in both groups, but viral load was significantly decreased in animals that received an IN vaccination (1.5 logs of infectious virus). No viral RNA or infectious virus was found in lung tissue of IN animals. A direct contact transmission model showed identical results; a significant reduction in shedding was detected in IN animals, but not IM animals. Prime-boost intranasal vaccination of rhesus macaques with ChAdOx1 nCoV-19 resulted in a robust humoral response. Intranasal shedding was reduced compared to shedding of control animals, and a reduction in viral load and infectious virus was detected in bronchoalveolar lavage fluid. A significantly reduced viral load was detected in lower respiratory tract tissue, like observed in the IM vaccinated animals in the previous experiment. In conclusion, intranasal vaccination reduced nasal shedding in two different SARS-CoV-2 animal models, and should be further investigated as a potential vaccination route for second or third generation COVID-19 vaccines to reduce or eliminate virus transmission.