TABLE 1.
Human CMV vaccine candidates in various stages of preclinical and clinical developmenta
| Category | Characteristics |
|---|---|
| Vaccines previously evaluated in clinical trials: not currently undergoing development | |
| AD169 vaccine | Engendered 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 vaccines | No 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 adjuvant | Favorable 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 vaccine | Venezuelan 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 vaccine | Favorable 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) vaccine | Favorable safety profile |
| Strong antibody and CD8+ cell-mediated immune responses (phase I) | |
| CMV vaccines currently undergoing evaluation in clinical trials | |
| V160-001 replication-defective vaccine | AD169 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 adjuvant | Lipidated 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” vaccine | Vectored 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 vaccine | Vectored 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 vaccine | DNA 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) vaccine | eVLPs 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 vaccines | Noninfectious |
| Humoral and cellular immune response in preclinical testing | |
| Contain gB, pp65, other envelope and tegument proteins | |
| RNA vaccines | Self-amplifying mRNA vaccines |
| Strong antibody and cell-mediated immune responses | |
| Platform currently under development by GSK Vaccines and Moderna Vaccines | |
| Electroporated DNA vaccines | DNA plasmid vaccines coadministered with electrical stimulation (SynCon platform) |
| Excellent immunogenicity in preclinical testing | |
| Platform under development by Inovio Vaccines | |
| RedBiotech gB/pp65 VLP vaccine | Engineered 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 vaccine | Soluble adjuvanted pentameric complex vaccine |
| Purified from CHO cells | |
| Potent, sustained neutralizing antibody responses in mice | |
| Developed by Humabs Biomed | |
| MVA-vectored PC vaccine | Based 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 protein | Designated 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.