ChAdOx1-S adenoviral vector vaccine applied intranasally elicits superior mucosal immunity compared to the intramuscular route of vaccination.

Abstract

COVID-19 vaccines prevent severe forms of the disease, but do not warrant complete protection against breakthrough infections. This could be due to suboptimal mucosal immunity at the site of virus entry, given that all currently approved vaccines are administered via the intramuscular route. In this study, we assessed humoral and cellular immune responses in BALB/c mice after intranasal and intramuscular immunization with adenoviral vector ChAdOx1-S expressing full-length Spike protein of SARS-CoV-2. We showed that both routes of vaccination induced a potent IgG antibody response, as well as robust neutralizing capacity, but intranasal vaccination elicited a superior IgA antibody titer in the sera and in the respiratory mucosa. Bronchoalveolar lavage from intranasally immunized mice efficiently neutralized SARS-CoV-2, which has not been the case in intramuscularly immunized group. Moreover, substantially higher percentages of epitope-specific CD8 T cells exhibiting a tissue resident phenotype were found in the lungs of intranasally immunized animals. Finally, both intranasal and intramuscular vaccination with ChAdOx1-S efficiently protected the mice after the challenge with recombinant herpesvirus expressing the Spike protein. Our results demonstrate that intranasal application of adenoviral vector ChAdOx1-S induces superior mucosal immunity and therefore could be a promising strategy for putting the COVID-19 pandemic under control.

• Authors: Maja Cokarić Brdovčak, Jelena Materljan, Marko Šustić, Sanda Ravlić, Tina Ružić, Berislav Lisnić, Karmela Miklić, Ilija Brizić, Marina Pribanić Matešić, Vanda Juranić Lisnić, Beata Halassy, Dobrica Rončević, Zdravka Knežević, Leo Štefan, Federico Bertoglio, Maren Schubert, Luka Čičin-Šain, Alemka Markotić, Stipan Jonjić, Astrid Krmpotić
• Journal: European journal of immunology (Eur J Immunol) Vol. 52 Issue 6 Pg. 936-945 (06 2022) ISSN: 1521-4141 [Electronic] Germany
• PMID: 35304741 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022 Wiley-VCH GmbH.

Chemical References

• Antibodies, Viral
• COVID-19 Vaccines
• Spike Glycoprotein, Coronavirus
• Viral Vaccines
• spike protein, SARS-CoV-2

Topics

• Adenoviridae (genetics)
• Administration, Intranasal
• Animals
• Antibodies, Viral
• COVID-19 (prevention & control)
• COVID-19 Vaccines
• Humans
• Immunity, Cellular
• Immunity, Mucosal
• Mice
• Mice, Inbred BALB C
• Pandemics (prevention & control)
• SARS-CoV-2
• Spike Glycoprotein, Coronavirus
• Vaccination (methods)
• Viral Vaccines