TY - JOUR
T1 - The role of vaccination route with an adenovirus-vectored vaccine in protection, viral control, and transmission in the SARS-CoV-2/K18-hACE2 mouse infection model
AU - Dickson, Alexandria
AU - Geerling, Elizabeth
AU - Stone, E. Taylor
AU - Hassert, Mariah
AU - Steffen, Tara L.
AU - Makkena, Taneesh
AU - Smither, Madeleine
AU - Schwetye, Katherine E.
AU - Zhang, Jianfeng
AU - Georges, Bertrand
AU - Roberts, M. Scot
AU - Suschak, John J.
AU - Pinto, Amelia K.
AU - Brien, James D.
N1 - Publisher Copyright:
Copyright © 2023 Dickson, Geerling, Stone, Hassert, Steffen, Makkena, Smither, Schwetye, Zhang, Georges, Roberts, Suschak, Pinto and Brien.
PY - 2023
Y1 - 2023
N2 - Introduction: Vaccination is the most effective mechanism to prevent severe COVID-19. However, breakthrough infections and subsequent transmission of SARS-CoV-2 remain a significant problem. Intranasal vaccination has the potential to be more effective in preventing disease and limiting transmission between individuals as it induces potent responses at mucosal sites. Methods: Utilizing a replication-deficient adenovirus serotype 5-vectored vaccine expressing the SARS-CoV-2 RBD (AdCOVID) in homozygous and heterozygous transgenic K18-hACE2, we investigated the impact of the route of administration on vaccine immunogenicity, SARS-CoV-2 transmission, and survival. Results: Mice vaccinated with AdCOVID via the intramuscular or intranasal route and subsequently challenged with SARS-CoV-2 showed that animals vaccinated intranasally had improved cellular and mucosal antibody responses. Additionally, intranasally vaccinated animals had significantly better viremic control, and protection from lethal infection compared to intramuscularly vaccinated animals. Notably, in a novel transmission model, intranasal vaccination reduced viral transmission to naïve co-housed mice compared to intramuscular vaccination. Discussion: Our data provide convincing evidence for the use of intranasal vaccination in protecting against SARS-CoV-2 infection and transmission.
AB - Introduction: Vaccination is the most effective mechanism to prevent severe COVID-19. However, breakthrough infections and subsequent transmission of SARS-CoV-2 remain a significant problem. Intranasal vaccination has the potential to be more effective in preventing disease and limiting transmission between individuals as it induces potent responses at mucosal sites. Methods: Utilizing a replication-deficient adenovirus serotype 5-vectored vaccine expressing the SARS-CoV-2 RBD (AdCOVID) in homozygous and heterozygous transgenic K18-hACE2, we investigated the impact of the route of administration on vaccine immunogenicity, SARS-CoV-2 transmission, and survival. Results: Mice vaccinated with AdCOVID via the intramuscular or intranasal route and subsequently challenged with SARS-CoV-2 showed that animals vaccinated intranasally had improved cellular and mucosal antibody responses. Additionally, intranasally vaccinated animals had significantly better viremic control, and protection from lethal infection compared to intramuscularly vaccinated animals. Notably, in a novel transmission model, intranasal vaccination reduced viral transmission to naïve co-housed mice compared to intramuscular vaccination. Discussion: Our data provide convincing evidence for the use of intranasal vaccination in protecting against SARS-CoV-2 infection and transmission.
KW - SARS-CoV-2
KW - intramuscular vaccination
KW - intranasal vaccination
KW - vaccine efficacy
KW - vaccine immunogenicity
KW - virus transmission
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U2 - 10.3389/fimmu.2023.1188392
DO - 10.3389/fimmu.2023.1188392
M3 - Article
C2 - 37662899
AN - SCOPUS:85169580235
VL - 14
JO - Frontiers in Immunology
JF - Frontiers in Immunology
M1 - 1188392
ER -
