TY - JOUR
T1 - Intranasal administration of adenoviral vaccines expressing SARS-CoV-2 spike protein improves vaccine immunity in mouse models
AU - Freitag, Tobias L.
AU - Fagerlund, Riku
AU - Karam, Nihay Laham
AU - Leppänen, Veli-Matti
AU - Ugurlu, Hasan
AU - Kant, Ravi
AU - Mäkinen, Petri
AU - Tawfek, Ahmed
AU - Kumar Jha, Sawan
AU - Strandin, Tomas
AU - Leskinen, Katarzyna
AU - Hepojoki, Jussi
AU - Kesti, Tapio
AU - Kareinen, Lauri
AU - Kuivanen, Suvi
AU - Koivulehto, Emma
AU - Sormunen, Aino
AU - Laidinen, Svetlana
AU - Khattab, Ayman
AU - Saavalainen, Päivi
AU - Meri, Seppo
AU - Kipar, Anja
AU - Sironen, Tarja
AU - Vapalahti, Olli
AU - Alitalo, Kari
AU - Ylä-Herttuala, Seppo
AU - Saksela, Kalle
PY - 2023/5/11
Y1 - 2023/5/11
N2 - 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.
AB - 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.
KW - SARS-CoV-2
KW - COVID-19
KW - intranasal vaccination
KW - mucosal immunity
KW - adenoviral vector
KW - Mucosal immunity
KW - Covid-19
KW - Adenoviral vector
KW - Intranasal vaccination
KW - 3111 Biomedicine
KW - 11832 Microbiology and virology
UR - https://www.scopus.com/pages/publications/85153057329
U2 - 10.1016/j.vaccine.2023.04.020
DO - 10.1016/j.vaccine.2023.04.020
M3 - Article
SN - 0264-410X
VL - 41
SP - 3233
EP - 3246
JO - Vaccine
JF - Vaccine
IS - 20
ER -