Background
Protective vaccines became an urgent need during the COVID-19 pandemic. People with immunodeficiencies particularly benefit from COVID-19 vaccination. PHH-1V (BIMERVAX®) is an authorized and adjuvanted recombinant vaccine based on a dimeric RBD of Alpha/Beta SARS-CoV-2 variants. HH-4 was a Phase IIb/III, open-label, single-arm, multi-center study (NCT05303402) to evaluate the humoral and cellular immune response elicited by PHH-1V booster in people with HIV-1 (PHW) and other immunodeficiencies considered to be at higher risk of adverse COVID-19 outcomes compared to the general population. Here, we evaluate cellular immune responses elicited by the PHH-1V booster in individuals with 5 different immunosuppressive conditions.
Methods
We analyzed the cellular immune responses after PHH-1V booster vaccination in cryopreserved PBMC samples at baseline (D0) and day 14 after vaccination (D14) in 5 immunosuppressed groups: people with HIV (PWH, n=30), kidney transplant (KTx, n=23), kidney disease on hemodialysis (HD, n=26), primary antibody deficiency disorders (PAD, n=18), and auto-immune disease on treatment with rituximab/ocrelizumab (AID, n=44). We measured total magnitude of T-cell responses and functionality by IFN-γ ELISpot and intracellular staining (ICS) assays, respectively, using 15-mer overlapping RBD 84-peptide pools of Omicron BA.1 and BA.2, Wuhan, B.1.351 (Beta, vaccine-matched) and B.1.617.2 (Delta). Mixed effects models were used on squared root transformed data stratified by sex.
Results
Total T-cell responses assessed by ELISpot significantly increased (p<0.05) in all the study groups, except for KTx, against the different SARS-CoV-2 pools. T-cell responses against Delta and Wuhan RBD pools were only found in PAD, PWH and AID groups, respectively. T-cell functionality also demonstrated a significant increase in IFN-γ secretion against SARS-CoV-2 peptides on CD4+ T-cells (RBD Omicron BA.1 in PWH and HD; RBD Omicron BA.2 in HD and PAD; RBD Beta in PWH and KTx, RBD Delta in AID; RBD Wuhan in PWH, HD and AID). Significant increases were observed in IL-2-producing CD4+ (RBD Omicron BA.2 in PAD) and in CD8+ T-cells (RBD Omicron BA.2 in HD and RBD Beta in PWH).
Conclusions
PHH-1V booster vaccination boosts cellular immunity against SARS-CoV-2 in PWH and a broad range of individuals with immunosuppressive conditions expanding specific IFN-γ+CD4+ T-cell phenotype across groups. The level of T-cell responses varies according to the underlying condition and/or its associated treatment.
Table or Figure
