ReviewVaccines

Priorities for developing respiratory syncytial virus vaccines in different target populations

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Science Translational Medicine  18 Mar 2020:
Vol. 12, Issue 535, eaax2466
DOI: 10.1126/scitranslmed.aax2466

Figures

  • Fig. 1 Structure of RSV.

    The RNA genome of RSV consists of 10 genes encoding 11 proteins. These proteins include two nonstructural proteins (NS1 and NS2); four envelope proteins: attachment glycoprotein (G), fusion protein (F), matrix protein (M), and small hydrophobic protein (SH); and five ribonucleocapsid proteins: nucleoprotein (N), phosphoprotein (P), large RNA polymerase (L), M2-1 (a zinc-binding transcription antiterminator), and M2-2 (a regulatory factor involved in the balance between RNA replication and transcription). In terms of vaccine development, the most important protein is the F protein. The F protein in the outer envelope of the RSV virion is highly conserved among RSV strains, making it an excellent potential vaccine target. The F protein has two forms, prefusion and postfusion, with the prefusion form being less stable but more immunogenic than the postfusion form [adapted from (132)].

    CREDIT: A. KITTERMAN/SCIENCE TRANSLATIONAL MEDICINE
  • Fig. 2 Different interventions tested in RSV clinical trials worldwide.

    The global map shows the distribution of all RSV vaccine and drug trials worldwide. The inset shows an expanded view of clinical trial sites in Scotland. Each dot on the global map represents a single clinical trial site and is color-coded according to the type of intervention tested. Dots are in translucent colors to prevent overlapping dots (depicting proximal trial sites) from obscuring each other. Blue dots represent biologicals (vaccines and monoclonal antibodies), red dots represent antiviral drugs, and yellow dots represent other study designs including observational studies. Clicking on the blue box connects to an interactive map (https://rsvclinicaltrials.org/interventions.html) where each clickable dot produces a popup box containing detailed information about a particular study site. Here, the popup box provides details of a clinical trial at a study site in Glasgow, UK, for evaluating the safety and efficacy of the antiviral drug suptavumab in preterm infants. Source data for this interactive map were downloaded from clinicaltrials.gov (in December 2019). The search term used in the “condition or disease” field was “Respiratory Syncytial Virus”. All clinical trials that fulfilled this search criterion were added to the source data file that was used to generate the maps.

    CREDIT: A. KITTERMAN/SCIENCE TRANSLATIONAL MEDICINE
  • Fig. 3 Global distribution of RSV clinical trials at different phases.

    Dots on the global map are color-coded according to the clinical trial phase: Phase 1 trials are shown in maroon, combined phase 1/2 trials are shown in dark red, and phase 2 trials are shown in light red. Combined phase 2/3 trials are shown in light blue and phase 3 trials are shown in dark blue. Purple dots indicate phase 4 trials. Dots are in translucent colors to prevent overlapping dots (depicting proximal trial sites) from obscuring each other. Clicking on the blue box connects to an interactive map (https://rsvclinicaltrials.org/phase.html) where each clickable dot produces a popup box containing detailed information about a particular study site. Here, the popup box provides details of a phase 1/2 trial of an adenovirus vector RSV vaccine in seronegative toddlers aged 12 to 24 months conducted at a trial site in Oxford, UK. Source data for this interactive map were downloaded from clinicaltrials.gov (in December 2019). The search term used in the “condition or disease” field was “Respiratory Syncytial Virus”. All clinical trials that fulfilled this search criterion were added to the source data file that was used to generate the maps.

    CREDIT: A. KITTERMAN/SCIENCE TRANSLATIONAL MEDICINE
  • Fig. 4 Status of RSV clinical trials worldwide.

    The recruitment status of different RSV vaccine and drug clinical trials as of December 2019 is shown. Yellow dots indicate trials that were active but had not yet started recruitment as of December 2019; red dots indicate completed trials. Green dots indicate inactive trials that had not yet begun recruitment as of December 2019; blue dots indicate trials that were actively recruiting in December 2019. Gray, purple, and black dots indicate trials that were terminated, of unknown status, or were halted, respectively. Dots are plotted in translucent colors to prevent overlapping dots (depicting proximal trial sites) from obscuring each other. Clicking on the blue box connects to an interactive map (https://rsvclinicaltrials.org/status.html) where each clickable dot produces a popup box containing detailed information about a particular study site. Here, the popup box provides details of a trial that evaluated an anti-RSV monoclonal antibody (MEDI-524) in children with congenital heart disease conducted at a trial site in Leeds, UK. Source data for this interactive map were downloaded from clinicaltrials.gov (in December 2019). The search term used in the “condition or disease” field was “Respiratory Syncytial Virus”. All clinical trials that fulfilled this search criterion were added to the source data file that was used to generate the maps.

    CREDIT: A. KITTERMAN/SCIENCE TRANSLATIONAL MEDICINE

Tables

  • Table 1 Published studies of recent RSV vaccine candidates tested in clinical trials in different population groups.

    Shaded cells signify that the study was carried out in that population. References are in parentheses.

    VaccineClassAdultsSeropositive childrenSeronegative
    children
    Pregnant womenOlder
    adults
    FI-RSV (14, 17)FIV*
    F, G, M subunit (89, 90)Subunit
    F-nanoparticle (55, 81)Nanoparticle
    Chimpanzee adenovirus RSV
    vaccine (39)
    VVV
    BBG2Na (91, 92)Subunit
    ΔM2-2 (93)LAV
    rA2cp248/404/1030ΔSH (94)LAV
    cpts530/1009 (35)LAV
    RSV ts-2 (95)LAV
    MEDI-559 (96)LAV
    MEDI-534 (9799)LAV
    RSV ts-1 A, B, and C (100, 101)LAV
    cpts248/955 (35)LAV
    cp-52B (102)LAV
    rA2cpΔNS2 (103)LAV
    cpRSV (104, 105)LAV
    RSV ts-1 (106108)LAV
    Cpts248/404 (109, 110)LAV
    rA2cp248/404ΔSH (94)LAV
    rA2cp248/404/1030ΔNS2 (103)LAV
    rA2cp530/1009ΔNS2 (103)LAV
    PFP1 (111116)Subunit
    PFP2 (110, 117121)Subunit
    PFP3 (122)Subunit
    MEDI-7510 (123)Subunit
    F nanoparticle (124, 125)Nanoparticle
    Pre-F (126)Subunit
    Soluble post-F (127)Subunit
    Small hydrophobic protein
    ectodomain (128)
    Subunit
    RSVcps2 (129)LAV
    LIDΔM2-2 (130)LAV
    RSV Pre-F (131)Recombinant

    *FIV, formalin-inactivated vaccine.

    †VVV, viral vector vaccine.

    ‡LAV, live-attenuated vaccine.

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