Live-Attenuated Respiratory Syncytial Virus Vaccine With Deletion of RNA Synthesis Regulatory Protein M2-2 and Cold Passage Mutations Is Overattenuated

Coleen K Cunningham; Ruth Karron; Petronella Muresan; Elizabeth J McFarland; Charlotte Perlowski; Jennifer Libous; Bhagvanji Thumar; Devasena Gnanashanmugam; Jack Moye Jr; Elizabeth Schappell; Emily Barr; Vivian Rexroad; Mariam Aziz; Jaime Deville; Richard Rutstein; Lijuan Yang; Cindy Luongo; Peter Collins; Ursula Buchholz; International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) 2012 Study Team

doi:10.1093/ofid/ofz212

Live-Attenuated Respiratory Syncytial Virus Vaccine With Deletion of RNA Synthesis Regulatory Protein M2-2 and Cold Passage Mutations Is Overattenuated

Open Forum Infect Dis. 2019 May 6;6(6):ofz212. doi: 10.1093/ofid/ofz212. eCollection 2019 Jun.

Authors

Coleen K Cunningham¹, Ruth Karron², Petronella Muresan³, Elizabeth J McFarland⁴, Charlotte Perlowski⁵, Jennifer Libous⁵, Bhagvanji Thumar², Devasena Gnanashanmugam⁶, Jack Moye Jr⁷, Elizabeth Schappell², Emily Barr⁴, Vivian Rexroad⁸, Mariam Aziz⁹, Jaime Deville¹⁰, Richard Rutstein¹¹, Lijuan Yang¹², Cindy Luongo¹², Peter Collins¹², Ursula Buchholz¹²; International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) 2012 Study Team

Affiliations

¹ Department of Pediatrics, Duke University Medical Center, Durham, North Carolina.
² Center for Immunization Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
³ Statistical & Data Analysis Center, Harvard T.H. Chan School of Public Health/Frontier Science, Boston, Massachusetts.
⁴ Department of Pediatrics, University of Colorado Anschutz Medical Campus and Children's Hospital Colorado, Aurora, Colorado.
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, Maryland.
⁷ Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland.
⁸ Investigational Drug Service Pharmacy, Johns Hopkins Hospital, Baltimore, Maryland.
⁹ Section of Infectious Disease, Rush University Medical Center, Chicago, Illinois.
¹⁰ Division of Pediatric Infectious Diseases, University of California, Los Angeles, California.
¹¹ Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
¹² Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.

Abstract

Background: The live respiratory syncytial virus (RSV) candidate vaccine LIDcpΔM2-2 is attenuated through deletion of M2-2 and 5 cold-passage mutations.

Methods: RSV-seronegative children aged 6-24 months received a single intranasal dose of 10⁵ plaque-forming units (PFU) of LIDcpΔM2-2 or placebo. RSV serum antibodies, vaccine infectivity, and reactogenicity were assessed.

Results: Four of 11 (36%) vaccinees shed vaccine virus with median peak titers of 1.6 log₁₀ PFU/mL by quantitative culture and 4.5 log₁₀ copies/mL by polymerase chain reaction; 45% had ≥4-fold rise in serum-neutralizing antibodies. Respiratory symptoms or fever were common in vaccinees (64%) and placebo recipients (6/6, 100%).

Conclusions: RSV LIDcpΔM2-2 is overattenuated. Clinical Trial Numbers. NCT02890381, NCT02948127.

Keywords: RNA regulatory protein M2-2; immunogenicity; live-attenuated viral vaccine; neutralizing antibodies; pediatric RSV vaccine; respiratory syncytial virus.

Associated data

ClinicalTrials.gov/NCT02890381
ClinicalTrials.gov/NCT02948127

Abstract

Associated data

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