TABLE 1

Human CMV vaccine candidates in various stages of preclinical and clinical developmenta

CategoryCharacteristics
Vaccines previously evaluated in clinical trials: not currently undergoing development
    AD169 vaccineEngendered CMV-specific antibodies in seronegative vaccinees
Injection site and systemic reactogenicity
    Towne vaccine (± rhIL-12)Elicitation of humoral and cellular immune responses
Safe; no latent infection or viral shedding in recipients
Reduction in CMV disease in renal transplant recipients
Coadministrated with recombinant IL-12 in phase I studies
    Towne/Toledo chimera vaccinesNo evidence for latency or shedding in recipients in phase I studies
Attenuated compared to Toledo strain of CMV
Variable immunogenicity in seronegatives
A mutation in UL128 abrogates formation of the PC in all four chimeras
    Subunit recombinant glycoprotein B (gB) (CHO cell expression), MF59/AS01 adjuvantFavorable safety evaluation in phase I
Neutralizing antibody and cell-mediated immune responses (limited to CD4+)
Boost of humoral immunity in seropositive recipients (gB/MF59)
Demonstrated efficacy in phase II studies in young women with respect to protection against primary CMV infection, and against development of CMV disease in seronegative SOT recipients with seropositive donors (gB/MF59)
    Alphavirus-vectored gB/pp65/IE1 vaccineVenezuelan equine encephalitis (VEE) vector
Towne gB (extracellular domain) and pp65-IE1 fusion protein expressed in a double-promoter replicon construct
Replication-deficient, virus-like replicon particles (VRP)
Humoral and cellular immune responses
    Canarypox-vectored glycoprotein B vaccineFavorable safety profile
No augmentation of immunogenicity in “prime-boost” study with gB/MF59
“Prime-boost” effect when administered with Towne vaccine
    Canarypox-vectored pp65 (UL83) vaccineFavorable safety profile
Strong antibody and CD8+ cell-mediated immune responses (phase I)
CMV vaccines currently undergoing evaluation in clinical trials
    V160-001 replication-defective vaccineAD169 backbone with restoration UL129/130/131 PC components
Disabled, single-cycle vaccine rendered replication incompetent by inclusion of ddFKBP/Shld1 in vaccine design
Administered with alum-based adjuvant
Phase I studies fully enrolled and data currently under analysis
    PADRE-pp65-CMV fusion peptide vaccines ± CpG DNA adjuvantLipidated fusion peptides constructed from pp65 CTL epitopes
Linked to a synthetically derived pan-DR or tetanus-derived epitope
Phase I studies currently ongoing
    Modified vaccinia virus ankara (MVA) “triplex” vaccineVectored delivery by attenuated poxvirus, MVA
Triplex vaccine: pp65, IE1/Exon 4, IE2/Exon 5
Favorable safety profile, T cell responses noted in CMV-seronegative recipients in phase I study
Vaccine under development at City of Hope, Duarte, California
    gB/pp65 lymphocytic choriomeningitis virus (LCMV)-vectored bivalent vaccineVectored vaccine designed using LCMV backbone
LCMV GP gene replaced by gB, pp65
Disabled, single round of replication
No antivector immunity (allows for boosting)
Virus-neutralizing antibody, cellular responses
    gB/pp65/IE1 trivalent DNA vaccine; gB/pp65 bivalent DNA vaccineDNA adjuvanted with poloxamer adjuvant and benzalkonium chloride
Both bivalent and trivalent vaccines evaluated in phase I studies
Impact on CMV disease in HSCT recipients demonstrated in phase II study with bivalent gB/pp65 vaccine
Phase III study of bivalent vaccine ongoing
Trivalent vaccine evaluated by coadministration with Towne vaccine in prime-boost vaccination
    Enveloped virus-like particle (eVLP) vaccineeVLPs formed by cotransfection of murine Moloney leukemia virus gag and CMV gB constructs
Expressed gB extracellular domain fused with transmembrane and cytoplasmic domains of vesicular stomatitis virus G protein
Positive immunogenicity and safety profile in phase I studies
Currently being developed by Variation Biotechnologies Vaccines Incorporated (VBI)
CMV vaccines in preclinical development
    Dense body vaccinesNoninfectious
Humoral and cellular immune response in preclinical testing
Contain gB, pp65, other envelope and tegument proteins
    RNA vaccinesSelf-amplifying mRNA vaccines
Strong antibody and cell-mediated immune responses
Platform currently under development by GSK Vaccines and Moderna Vaccines
    Electroporated DNA vaccinesDNA plasmid vaccines coadministered with electrical stimulation (SynCon platform)
Excellent immunogenicity in preclinical testing
Platform under development by Inovio Vaccines
    RedBiotech gB/pp65 VLP vaccineEngineered using recombinant baculovirus
Generation of virus-like replicon particles (VRPs)
Phase I clinical trial recently initiated
Virus-neutralizing antibody and cell-mediated immune responses
Currently being developed by Pfizer Vaccines
    Soluble PC vaccineSoluble adjuvanted pentameric complex vaccine
Purified from CHO cells
Potent, sustained neutralizing antibody responses in mice
Developed by Humabs Biomed
    MVA-vectored PC vaccineBased on CMV PC
Induces ELISA and neutralizing antibodies in mice
Antibodies capable of blocking CMV infection of fetal placental macrophages (Hofbauer cells)
    MVA-vectored pp65/IE1 fusion proteinDesignated MVA-syn65_IE1
Expands pp65- and IE1-specific T cells derived from CMV-seropositive donors
Induces CMV pp65- and IE1 epitope-specific T cells in HLA-transgenic mice
    Adenovirus-vectored gB/polyepitope (Ad-gBCMV polyvaccine)Based on a replication-deficient adenovirus
Encodes a truncated form of CMV-encoded gB antigen and multiple CMV T-cell epitopes from eight different CMV antigens as a single fusion protein
Immunogenic in preclinical studies in HLA-A2 transgenic mice
  • a ELISA, enzyme-linked immunosorbent assay; rhIL-12, recombinant human interleukin-12.