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

Abstract

Intranasal vaccination of hamsters and rhesus macaques with ChAdOx1 nCoV-19 reduces shedding of SARS-CoV-2 after challenge. Intranasal SARS-CoV-2 vaccination Protection conferred by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines may be influenced by the route of immunization. As SARS-CoV-2 is a respiratory pathogen, vaccinating intranasally may provide enhanced protection within the respiratory tract. To investigate this possibility, van Doremalen et al. vaccinated hamsters and rhesus macaques intranasally with ChAdOx1 nCoV-19/AZD1222, an adenovirus-vectored vaccine in clinical use. In both models, intranasal vaccination reduced viral shedding after SARS-CoV-2 challenge relative to control animals. In hamsters, intranasal vaccination generated increased neutralizing antibody titers as compared to intramuscular vaccination, although both routes were effective at reducing viral loads. Together, these data support further investigation into intranasal vaccination with ChAdOx1 nCoV-19/AZD1222. 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.