Abstract
Current vaccines have greatly diminished the severity of the COVID-19 pandemic, even though they do not entirely prevent infection and transmission, likely due to insufficient immunity in the upper respiratory tract. Here, we compare intramuscular and intranasal administration of a live, replication-deficient modified vaccinia virus Ankara (MVA)-based Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) spike (S) vaccine to raise protective immune responses in the K18-hACE2 mouse model. Using a recombinant MVA expressing firefly luciferase for tracking, live imaging revealed luminescence of the respiratory tract of mice within 6 h and persisting for 3 d following intranasal inoculation, whereas luminescence remained at the site of intramuscular vaccination. Intramuscular vaccination induced S-binding-Immunoglobulin G (IgG) and neutralizing antibodies in the lungs, whereas intranasal vaccination also induced Immunoglobulin A (IgA) and higher levels of antigen-specific CD3 + CD8 + IFN-γ + T cells. Similarly, IgG and neutralizing antibodies were present in the blood of mice immunized intranasally and intramuscularly, but IgA was detected only after intranasal inoculation. Intranasal boosting increased IgA after intranasal or intramuscular priming. While intramuscular vaccination prevented morbidity and cleared SARS-CoV-2 from the respiratory tract within several days after challenge, intranasal vaccination was more effective as neither infectious virus nor viral messenger (m)RNAs were detected in the nasal turbinates or lungs as early as 2 d after challenge, indicating prevention or rapid elimination of SARS-CoV-2 infection. Additionally, we determined that neutralizing antibody persisted for more than 6 mo and that serum induced to the Wuhan S protein neutralized pseudoviruses expressing the S proteins of variants, although with less potency, particularly for Beta and Omicron.
Keywords: COVID-19; coronavirus vaccine; mucosal immunity; respiratory immunity; vaccinia virus.
【저자키워드】 COVID-19, mucosal immunity, coronavirus vaccine, vaccinia virus., respiratory immunity, 【초록키워드】 severe acute respiratory syndrome coronavirus 2, neutralizing antibody, SARS-CoV-2, IgG, Vaccine, coronavirus, vaccination, Immunity, S protein, Neutralizing antibodies, T cells, SARS-COV-2 infection, COVID-19 pandemic, severity, Infection, lung, Transmission, severe acute respiratory syndrome Coronavirus, omicron, CD8, coronavirus 2, variants, Antigen, serum, Immunoglobulin G, Viral, Immunoglobulin, mice, IgA, immune responses, Lungs, Wuhan, morbidity, Beta, vaccinia virus, coronavirus vaccine, respiratory tract, respiratory, immunoglobulin A, upper respiratory tract, intranasal, Blood, Luminescence, IFN-γ, intramuscular, K18-hACE2, mucosal, administration, Infectious virus, nasal turbinate, nasal turbinates, pseudoviruses, acute respiratory syndrome, protective immune response, S proteins, priming, luciferase, while, modified vaccinia virus, intramuscular vaccination, CD3, Prevent, effective, immunized, current, neutralized, firefly luciferase, raise, intranasally, remained, less, the S protein, prevented, expressing, intramuscularly, pseudovirus, 【제목키워드】 Vaccine, hACE2, IgA, PROTECT, induce,