Journal Article

Intranasal administration of adenoviral vaccines expressing SARS-CoV-2 spike protein improves vaccine immunity in mouse models

Tawfek, Ahmed, Saksela, Kalle, Vapalahti, Olli, Alitalo, Kari, Kareinen, Lauri, Khattab, Ayman, Freitag, Tobias L., Strandin, Tomas, Sormunen, Aino, Fagerlund, Riku, Kuivanen, Suvi, Ugurlu, Hasan, Karam, Nihay Laham, Kesti, Tapio, Laidinen, Svetlana, Jha, Sawan Kumar, Saavalainen, Päivi, Leskinen, Katarzyna, Leppänen, Veli-Matti, Mäkinen, Petri, Hepojoki, Jussi, Ylä-Herttuala, Seppo, Sironen, Tarja, Koivulehto, Emma, Kant, Ravi, Kipar, Anja, Meri, Seppo

2023

Overview

The ongoing SARS-CoV-2 pandemic is controlled but not halted by public health measures and mass vaccination strategies which have exclusively relied on intramuscular vaccines. Intranasal vaccines can prime or recruit to the respiratory epithelium mucosal immune cells capable of preventing infection. Here we report a comprehensive series of studies on this concept using various mouse models, including HLA class II-humanized transgenic strains. We found that a single intranasal (i.n.) dose of serotype-5 adenoviral vectors expressing either the receptor binding domain (Ad5-RBD) or the complete ectodomain (Ad5-S) of the SARS-CoV-2 spike protein was effective in inducing i) serum and bronchoalveolar lavage (BAL) anti-spike IgA and IgG, ii) robust SARS-CoV-2-neutralizing activity in the serum and BAL, iii) rigorous spike-directed T helper 1 cell/cytotoxic T cell immunity, and iv) protection of mice from a challenge with the SARS-CoV-2 beta variant. Intramuscular (i.m.) Ad5-RBD or Ad5-S administration did not induce serum or BAL IgA, and resulted in lower neutralizing titers in the serum. Moreover, prior immunity induced by an intramuscular mRNA vaccine could be potently enhanced and modulated towards a mucosal IgA response by an i.n. Ad5-S booster. Notably, Ad5 DNA was found in the liver or spleen after i.m. but not i.n. administration, indicating a lack of systemic spread of the vaccine vector, which has been associated with a risk of thrombotic thrombocytopenia. Unlike in otherwise genetically identical HLA-DQ6 mice, in HLA-DQ8 mice Ad5-RBD vaccine was inferior to Ad5-S, suggesting that the RBD fragment does not contain a sufficient collection of helper-T cell epitopes to constitute an optimal vaccine antigen. Our data add to previous promising preclinical results on intranasal SARS-CoV-2 vaccination and support the potential of this approach to elicit mucosal immunity for preventing transmission of SARS-CoV-2.

• Publisher: Elsevier Ltd,Elsevier Limited,The Author(s). Published by Elsevier Ltd
• Subject: Adenoviral vector / Adenoviridae / Administration, Intranasal / Allergy and Immunology / Animal models / Animals / Antibodies / Antibodies, Neutralizing / Antibodies, Viral / Antigens / blood serum / Bronchus / CD4-positive T-lymphocytes / class / Coronaviruses / COVID-19 / COVID-19 - prevention & control / COVID-19 Vaccines / Cytotoxicity / Disease Models, Animal / Disease transmission / DNA / domain / Epithelium / Epitopes / Expression vectors / genetically modified organisms / Histocompatibility antigen HLA / Humans / Immune system / Immunity / Immunoglobulin A / Immunoglobulin G / Infections / Intranasal administration / Intranasal vaccination / Lavage / liver / Lymphocytes / Lymphocytes T / Mice / mRNA / Mucosal immunity / Neutralizing / pandemic / Pandemics / Proteins / Public health / respiratory mucosa / Respiratory tract / risk / SARS-CoV-2 / Severe acute respiratory syndrome coronavirus 2 / Spike Glycoprotein, Coronavirus - genetics / Spike protein / Spleen / Thrombocytopenia / Trends / vaccination / Vaccines / Vectors (Biology) / Viral diseases / Viral Vaccines