Background
PHH-1V (BIMERVAX®) is an adjuvanted recombinant protein vaccine based on a dimeric RBD of the Alpha/Beta SARS-CoV-2 variants. In march 2023 PHH-1V received full marketing approval by EMA (European Medicines Agency) to be used as a heterologous booster for preventing coronavirus disease 2019 (COVID-19) in people aged 16 and older. The HH-3 study (Phase IIb, Open-label, Multi-center, Non-Inferiority, NCT06234956) aims to assess the safety and immunogenicity of PHH-1V in 300 healthy adolescents (pediatric population), with ages comprised 12 to 17 years, that had been previously vaccinated with mRNA-based SARS-CoV-2 vaccines. Here, we evaluate the T-cell immune response in a group of 16 study participants.
Methods
Cryopreserved peripheral blood mononuclear cells (PBMC) samples were obtained from participants (n=16) on baseline (D0) and day 14 (D14) after receiving the PHH-1V booster. PBMCs were isolated and stimulated with 15-mer overlapping peptides pools (84 peptides) covering the RBD region of the Spike protein from the RBD Omicron BA.1 and RBD B.1.351 (Beta) variants of the SARS-CoV-2 virus. T-cell responses were evaluated using ELISpot and Intracellular Cytokine Staining (ICS) techniques. We measured the magnitude of IFNγ T-cell responses by ELISpot assay (Spot Forming Units, SFU per million) after a 24-hour peptide stimulation. ICS measured percentages of IFNγ, IL-2 and IL-4 secreting CD4 and CD8 T-cells after 6 hours of peptide stimulation.
Results
ELISpot assay showed a significant increase in IFNγ-producing T cells at D14 after vaccination with both RBD peptide pools tested (RBD B.1.351 p<0.0001, RBD Omicron BA.1 p<0.0001). ICS assay demonstrated that most of the IFNγ secreting cells have a CD4+ T-cell phenotype (RBD B.1.351 p<0.0001, RBD Omicron BA.1 p=0.0002), although an increase of IL-4 secreting CD4+ T-cells was detected against peptides from the B.1.351 variant (p=0.0381). A non-significant increase of IFNγ CD8 T-cell responses was detected against the B.1.351 variant. No increases in IL-2-producing CD4 and CD8 T cells were observed.
Conclusions
PHH-1V vaccine elicits a robust IFNγ T cell response in healthy pediatric adolescents when administered as a heterologous boost. Our findings are similar to those obtained in the heterologous boost study with healthy adults aged 18 to 65 years old (HIPRA HH-2). Noteworthy, the present study indicates a more pronounced IFNγ T cell immune response in adolescents than adults, potentially reflecting their maturating immune system.