Safety and immunogenicity of a cytomegalovirus (CMV) recombinant glycoprotein B (gB) vaccine in combination with polyacrylate or an emulsion-based adjuvants.

BACKGROUND

SPA09, a polyacrylate adjuvant, is currently being evaluated for use in human vaccines. This first-in-human clinical trial compared the safety and immunogenicity of two SPA09 (polyacrylate)-adjuvanted (low-dose [LD] and high-dose [HD]) cytomegalovirus glycoprotein B (CMV-gB) formulations to an AF03 (emulsion)-adjuvanted CMV-gB formulation as a benchmark.

METHODS

Healthy CMV-seronegative adults aged 18 to <50 years were randomized (1:1:1) to receive three intramuscular doses of CMV-gB/AF03 (N = 34), CMV-gB/SPA09LD (N = 36), or CMV-gB/SPA09HD (N = 34) on day (D) 0, D56, and D180. Follow-up included safety outcomes (reactogenicity, adverse events) and measurement of biochemical/hematological parameters. Immunogenicity assessment included CMV-neutralizing antibody titers, antigen-specific serum immunoglobulin G (IgG) antibody levels and IgG subclass distribution, as well as frequencies of memory B cells, CMV-gB-specific cytokine secreting T cells, T follicular helper cells, and plasmablasts.

RESULTS

All vaccines had acceptable safety profiles with no safety concerns identified. Reactogenicity tended to increase with the number of SPA09-adjuvanted vaccine doses, including a higher proportion of grade 3 reactions, which was more pronounced with CMV-gB/SPA09HD. The proportion of participants reporting solicited reactions was comparable between the CMV-gB/SPA09LD and CMV-gB/AF03 groups. Out-of-normal-range laboratory parameters were mainly of grades 1-2. Both SPA09-adjuvanted formulations induced significantly higher CMV-neutralizing antibody titers and CMV-binding IgG titers than the CMV-gB/AF03 vaccine (predominantly IgG1, irrespective of adjuvant), as well as higher frequencies of memory B cells, cytokine secreting T cells, and plasmablasts. SPA09-adjuvanted formulations induced higher interferon-γ and interleukin-4 secreting T cell frequencies, with a Th1-biased profile, whereas the AF03-adjuvanted vaccine induced a more Th2-biased profile. Immune responses decreased six months after the third dose across all three groups but persisted at the level observed after the second dose.

CONCLUSIONS

CMV-gB/SPA09LD demonstrated a better safety profile than CMV-gB/SPA09HD, with comparable immunogenicity, while also offering an adjuvant-enhanced immunogenicity effect compared to CMV-gB/AF03.

CLINICAL TRIAL REGISTRATION: WHO identifier: U1111-1217-1910; EU trial number: 2019-001333-14.