期刊
VACCINE
卷 39, 期 30, 页码 4063-4071出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.vaccine.2021.06.013
关键词
Respiratory syncytial virus; Mnull RSV accine; RSV vaccine; Infant baboon odel; Bronchiolitis
资金
- Oklahoma Center for Advancement of Science and Technology (OCAST) [HR13033]
- Children's Hospital Foundation HobbsRecknagel Endowed Chair in Pediatrics
RSV is a major viral respiratory pathogen for infants and children, with no licensed vaccine available. A vaccine has been developed using a human RSV strain with the M protein gene deleted, preventing viral replication. Vaccination led to reduced illness signs and viral replication in infected animals, supporting further development for human use.
Respiratory syncytial virus (RSV) is the major viral respiratory pathogen for human infants and children. Despite a severe global burden incurred by annual RSV epidemics, there is no licensed RSV vaccine. We have developed an RSV vaccine from a human RSV strain from which the gene for the viral M protein has been deleted (Mnull RSV). RSV infects airway cells and produces each of its proteins. The M protein is responsible for reassembling the various other synthesized viral proteins into new, intact virus. In the absence of the M protein, therefore, reassembly does not occur, and the Mnull RSV does not replicate. We vaccinated 2-week old infant baboons with Mnull RSV either intranasally (IN) or directly into the lung (intratracheal, or IT), then infected these animals by inoculating human RSV directly into the lung. IN vaccination induced inconsistent serum RSV neutralizing antibody (NA) responses, but provided moderate reductions in respiratory rates, overall signs of illness and viral replication in bronchoalveolar lavage (BAL) fluid following infection. Intratracheal vaccination induced much stronger RSV NA responses, which persisted for at least 4-6 months. Following RSV infection, animals vaccinated by the IT route had much greater reductions in tachypnea and work of breathing than animals vaccinated IN, and had undetectable amounts of virus in BAL fluids. These results support the further development of IT Mnull RSV vaccination to reduce the impact of RSV infection in humans. (c) 2021 Published by Elsevier Ltd.
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