1922. Safety and immunogenicity of the recombinant live-attenuated respiratory syncytial virus vaccine RSV cps2 in RSV-seronegative infants and children
Session: Poster Abstract Session: Vaccines: RSV
Saturday, October 10, 2015
Room: Poster Hall
  • IMPAACT P1114 ID WeekFinal.pdf (594.7 kB)
  • Background: Respiratory Syncytial Virus (RSV) is an important pathogen in infants and young children. Live attenuated RSV vaccines are a promising approach to induce RSV immunity without disease enhancement.  This study evaluated the attenuated vaccine RSVcps2, a genetically stabilized version of rA2cp248/404/1030DSH containing five independent attenuating elements.

    Methods: This phase I, double blind, placebo controlled study randomized (2:1) RSV-seronegative children 6 to 24 months of age to receive a single intranasal dose of vaccine (RSVcps2) or placebo. Children were monitored with frequent contacts (including nasal wash (NW) samples on >11 occasions through day 28) during the first 56 days and weekly during the RSV season (November-March). Infectivity was determined by quantitative culture (plaque forming units (PFU)/mL) and rRT qPCR (copies/mL) in NW fluid. NW fluid was tested for respiratory viral pathogens by Fast Track PCR when respiratory symptoms were reported.

    Results: Fifty-one children were enrolled from five sites in October, 2013 (17 children) and between April and October, 2014 (34 children); enrollment was suspended during the intervening RSV season. Fifty children received study product and completed the study. The average age was 12 months (range 6-23 months); 58% were male, 28% were Black and 47% were HIV-exposed but uninfected.  Vaccine and placebo recipients commonly experienced mild and moderate adverse events, primarily respiratory illnesses that occurred in 44% of both groups.  No Grade 4 or serious adverse events occurred.  Twenty-six of 34 (77%) vaccine recipients had vaccine shedding detected by viral culture (15 vaccinees) or qPCR (26 vaccinees).  Among those who tested positive, the mean peak titer by culture was 1.7 log10 PFU/ml (SD=1.0) and the mean peak titer by qPCR was 3.3 log10 copies/mL (SD=0.9). No placebo recipients had vaccine virus detected.  There was no evidence of RSV disease enhancement when RSV infection occurred during RSV season.  Determination of neutralizing antibody responses and RSV F IgG antibody responses is in progress.

    Conclusion: The RSVcps2 vaccine has excellent infectivity and is well tolerated in sero-negative infants and children.  Further evaluation of this candidate vaccine is warranted.

    Coleen K. Cunningham, MD1, Ursula Buchholz, Ph.D.2, Petronella Muresan, MS3, Elizabeth Mcfarland, MD4, Cindy Luongo, Ph, D.5, Peter Collins, Ph.D6, Bhagvanji Thumar, Ph.D.7, Elizabeth Schappell, RN, BSN, CCRP7, Devasena Gnanashanmugam, MD8, George Siberry, MD, MPH, FPIDS9, Vivian Rexroad, Pharm.D.10 and Ruth Karron, MD11, (1)Pediatrics, Division of Infectious Diseases, Department of Pediatrics, Duke University Medical Center, Durham, NC, (2)Laboratory of Infectious Diseases (LID), National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, MD, (3)Harvard School of Public Health, Boston, MA, (4)Department of Infectious Disease, University of Colorado School of Medicine, Aurora, CO, (5)National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, MD, (6)Laboratory of Infectious Diseases (LID), National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, (7)Center for Immunization Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, (8)Maternal, Adolescent and Pediatric Research Branch, PSP/DAIDS/NIAID/NIH, Bethesda, MD, (9)Maternal and Pediatric Infectious Disease Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD, (10)Investigational Drug Service Pharmacy, Johns Hopkins Hospital, Baltimore, MD, (11)Johns Hopkins Bloomberg School of Public Health, Baltimore, MD


    C. K. Cunningham, None

    U. Buchholz, Medimmune, LLC: Collaborator , Research support

    P. Muresan, None

    E. Mcfarland, None

    C. Luongo, None

    P. Collins, MedImmune: Collaborative Research Agreement (CRADA) , Research support

    B. Thumar, None

    E. Schappell, None

    D. Gnanashanmugam, None

    G. Siberry, None

    V. Rexroad, None

    R. Karron, NIH: Research Contractor , Research support

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