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J Infect Dis. 2018 Apr 11;217(9):1347-1355. doi: 10.1093/infdis/jiy040.

Live-Attenuated Respiratory Syncytial Virus Vaccine Candidate With Deletion of RNA Synthesis Regulatory Protein M2-2 is Highly Immunogenic in Children.

Author information

1
Department of Pediatrics, University of Colorado Anschutz Medical Campus and Children's Hospital Colorado, Aurora.
2
Center for Immunization Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
3
Statistical and Data Analysis Center, Harvard School of Public Health, Boston, Massachusetts.
4
Department of Pediatrics, Duke University Medical Center.
5
FHI 360, Durham, North Carolina.
6
Maternal, Adolescent and Pediatric Research Branch, Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda.
7
Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda.
8
Investigational Drug Service Pharmacy, Johns Hopkins Hospital, Baltimore, Maryland.
9
Department of Pediatrics, Northwestern University Medical School and Ann and Robert H. Lurie Children's Hospital of Chicago, Illinois.
10
Department of Pediatrics, University of California San Diego, La Jolla.
11
Section of Infectious Disease, Rush University Medical Center, Chicago, Illinois.
12
Department of Pediatrics, St. Jude Children's Research Hospital, Memphis, Tennessee.
13
Division of Infectious Diseases, Maternal Child and Adolescent Center, University of Southern California Keck School of Medicine, Los Angeles.
14
Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryl.

Abstract

Background:

Live respiratory syncytial virus (RSV) candidate vaccine LIDΔM2-2 is attenuated by deletion of the RSV RNA regulatory protein M2-2, resulting in upregulated viral gene transcription and antigen expression but reduced RNA replication.

Methods:

RSV-seronegative children ages 6-24 months received a single intranasal dose of 105 plaque forming units (PFU) of LIDΔM2-2 (n = 20) or placebo (n = 9) (NCT02237209, NCT02040831). RSV serum antibodies, vaccine infectivity, and reactogenicity were assessed. During the following RSV season, participants were monitored for respiratory illness and pre- and post-RSV season serum antibodies.

Results:

Vaccine virus was shed by 95% of vaccinees (median peak titers of 3.8 log10 PFU/mL by quantitative culture and 6.3 log10 copies/mL by PCR); 90% had ≥4-fold rise in serum neutralizing antibodies. Respiratory symptoms and fever were common in vaccine (95%) and placebo (78%). One vaccinee had grade 2 rhonchi concurrent with vaccine shedding, rhinovirus, and enterovirus. Eight of 19 vaccinees versus 2 of 9 placebo recipients had substantially increased RSV antibody titers after the RSV season without medically attended RSV disease, indicating anamnestic vaccine responses to wild-type RSV without significant illness.

Conclusion:

LIDΔM2-2 had excellent infectivity and immunogenicity, encouraging further study of vaccine candidates attenuated by M2-2 deletion.

Clinical Trials Registration:

NCT02237209, NCT02040831.

PMID:
29509911
PMCID:
PMC5894092
DOI:
10.1093/infdis/jiy040
[Indexed for MEDLINE]
Free PMC Article

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