Intranasal and intrapulmonary vaccination with an M protein-deficient respiratory syncytial virus (RSV) vaccine improves clinical signs and reduces viral replication in infant baboons after an RSV challenge infection.

Autor: Ivanov V; Department of Pediatrics, College of Medicine, University of Oklahoma Health Sciences Center, 1100 North Lindsay Ave., Oklahoma City, OK 73104, USA. Electronic address: Vadim-Ivanov@OUHSC.edu., Oomens AGP; Department of Veterinary Pathology, College of Veterinary Medicine, Room 258 McElroy Hall, Oklahoma State University, Stillwater, OK 74074, USA. Electronic address: Oomens@OKState.edu., Papin JF; Division of Comparative Medicine, The University of Oklahoma, Health Sciences Center, 940 Stanton L. Young Blvd., Oklahoma City, OK 73104, USA. Electronic address: James-Papin@OUHSC.edu., Staats R; Department of Pediatrics, College of Medicine, University of Oklahoma Health Sciences Center, 1100 North Lindsay Ave., Oklahoma City, OK 73104, USA. Electronic address: Rachel-Staats@OUHSC.edu., Reuter DN; Division of Comparative Medicine, The University of Oklahoma, Health Sciences Center, 940 Stanton L. Young Blvd., Oklahoma City, OK 73104, USA. Electronic address: Darlene-Reuter@OUHSC.edu., Yu Z; Department of Pathology, College of Medicine, University of Oklahoma Health Sciences Center, 1100 North Lindsay Ave., Oklahoma City, OK 73104, USA. Electronic address: Zhongxin-Yu@OUHSC.edu., Piedra PA; Department of Molecular Biology and Microbiology and Pediatrics, Baylor College of Medicine, Baylor University, 1 Baylor Plaza, Houston, TX 77030, USA. Electronic address: PPiedra@BCM.edu., Wellliver RC Sr; Department of Pediatrics, College of Medicine, University of Oklahoma Health Sciences Center, 1100 North Lindsay Ave., Oklahoma City, OK 73104, USA. Electronic address: Robert-Welliver@OUHSC.edu.
Jazyk: angličtina
Zdroj: Vaccine [Vaccine] 2021 Jul 05; Vol. 39 (30), pp. 4063-4071. Date of Electronic Publication: 2021 Jun 14.
DOI: 10.1016/j.vaccine.2021.06.013
Abstrakt: 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.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2021. Published by Elsevier Ltd.)
Databáze: MEDLINE
Externí odkaz: