1924. High infectivity of recombinant live-attenuated respiratory syncytial virus vaccine (RSV LID ΔM2-2) in infants and children
Session: Poster Abstract Session: Vaccines: RSV
Saturday, October 10, 2015
Room: Poster Hall
  • IMPAACT 2000 ID Week poster 9-30-15.3.pdf (622.3 kB)
  • Background: Live-attenuated RSV vaccines are a promising approach to induce RSV immunity in infants and young children without disease enhancement.  This study evaluated an intranasal (IN) RSV vaccine, attenuated by deletion of the RSV RNA regulatory factor M2-2.

    Methods: In a phase I, double blind, placebo controlled study, RSV-seronegative children (aged 6-24 months) were randomized (2:1) to receive a single IN dose of vaccine (RSV LID ΔM2-2) or placebo. Children were monitored with frequent contacts (including nasal washes (NW) on >11 occasions through day 28) during the first 56 days and weekly during the subsequent RSV season. Infectivity was determined by quantitative culture (plaque forming units (PFU)/ml) and rRT qPCR (copies/ml) performed on NWs. NWs were tested for respiratory pathogens by Fast Track PCR when respiratory symptoms were reported. The study was not powered for formal statistical comparison between arms.

    Results: During September-October 2014, 20 vaccine and 9 placebo recipients enrolled with mean (SD) age 12.5 (­+6.1) and 9.1 (+3.1) months, respectively. Participants were 52% male, 48% African American, and 38% HIV exposed, uninfected. Vaccine shedding was detected in 95% of vaccine and no placebo recipients.  Duration of vaccine shedding by culture and qPCR was a mean (maximum) of 9 (14) and 12.7 (17) days and mean (SD) peak titers were 3.4 (+1.5) log10 PFU/ml and 5.9 (+1.3) log10 copies/ml, respectively. During the monitoring period there were no grade 4 or serious adverse events; there was 1 grade 3 fever in a vaccinee. A study pause was triggered by grade 2 rhonchi in a vaccine recipient temporally associated with shedding of vaccine virus as well as rhinovirus and enterovirus. During post-inoculation monitoring, mild or moderate respiratory illness and/or fever occurred frequently in both groups (19/20 vaccine and 7/9 placebo recipients). During RSV season, medically attended respiratory illness or fever occurred in 7/20 vaccine (0 RSV+) and 6/9 placebo (1 RSV+) recipients.

    Conclusion: The RSV LID ΔM2-2 vaccine had excellent infectivity in sero-negative infants and children; however, peak vaccine shedding titers were higher than desirable, and additional attenuation will be needed for further development of this candidate vaccine.

    Elizabeth Mcfarland, MD1, Ursula Buchholz, Ph.D.2, Petronella Muresan, MS3, Coleen K. Cunningham, MD4, Cindy Luongo, Ph.D.2, Bhagvanji Thumar, Ph.D.5, Peter Collins, Ph.D6, Charlotte Perlowski, MSPH7, Elizabeth Schappell, RN, BSN, CCRP5, Devasena Gnanashanmugam, MD8, George Siberry, MD, MPH, FPIDS9, Vivian Rexroad, Pharm.D.10, Emily Barr, CPNP, CNM, MSN11, Paul Harding, MS11, Ruth Karron, MD12 and the IMPAACT 2000 Team, (1)Department of Infectious Disease, University of Colorado School of Medicine, Aurora, CO, (2)Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, (3)Harvard School of Public Health, Boston, MA, (4)Pediatrics, Division of Infectious Diseases, Department of Pediatrics, Duke University Medical Center, Durham, NC, (5)Center for Immunization Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, (6)Laboratory of Infectious Diseases (LID), National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, (7)FHI 360, Durham, NC, (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)University of Colorado School of Medicine, Aurora, CO, (12)Johns Hopkins Bloomberg School of Public Health, Baltimore, MD


    E. Mcfarland, None

    U. Buchholz, None

    P. Muresan, None

    C. K. Cunningham, None

    C. Luongo, None

    B. Thumar, None

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

    C. Perlowski, None

    E. Schappell, None

    D. Gnanashanmugam, None

    G. Siberry, None

    V. Rexroad, None

    E. Barr, None

    P. Harding, None

    R. Karron, NIH: Research Contractor , Research support

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