Background:
In the current Omicron era of COVID-19 pandemic, boosters with variant-adapted mRNA vaccines are recommended for fragile populations to provide broad protection against newly emergent SARS-CoV-2 variants. While previous studies showed enhanced neutralization against Omicron sub-lineages after a bivalent booster, data on T-cell immunity are limited, especially in PWH. We assessed humoral and T-cell responses to an original/BA.4-5 booster in this population.
Methods:
PWH on ART receiving a bivalent booster as fourth dose were enrolled. We measured immune responses against WT and BA.4-5 virus: RBD-binding Abs (ELISA); RBD-blocking Abs (RBD-ACE2 binding inhibition assay); Th1/Tc1 cytokine (IFN-γ/TNF-α/IL-2)-producing and cytotoxic (CD107a+) CD4/CD8 T-cells (flow cytometry after PBMCs stimulation with spike peptides) before (T0) and 1 month after (T1) the 4th dose. Wilcoxon test was used for statistical analyses.
Results:
We included 30 PWH who received the 4th dose at a median time of 14.5 (IQR: 13.5–15) months after the 3rd one. Median CD4 T-cell count was 790/µL (IQR: 598–929) and HIV-RNA <20 copies/mL. Demographic and viro-immunologic features are reported in Fig.1A. The 4th dose led to an increase of RBD-binding/blocking Abs against both WT and BA.4-5 (Fig.1B–C). Interestingly, when compared to WT, BA.4-5–specific humoral immunity was lower at both T0 and T1 (Fig.1B–C). Frequencies of Th1/Tc1 and cytotoxic CD4/CD8 T-cells against WT and BA.4-5 did not increase after the booster, with similar values of WT– and BA.4-5–specific responses both before and after the booster administration (Fig.1D–G). Despite stable frequencies, polyfunctionality of WT/BA.4-5–specific T-cells was increased after the booster (Fig.1H–J), and yet the proportion of BA.4-5–specific polyfunctional IFN-γ+TNF-α+IL-2+/IFN-γ+TNF-α+IL-2– CD4 T-cells and IFN-γ+TNF-α+IL-2– CD8 T-cells were lower than WT–specific ones at all time-points (Fig.1H–J).
Conclusions:
In PWH on effective ART, an original/BA.4-5 bivalent booster increases RBD-binding/blocking Abs and T-cell polyfunctionality against both WT and BA.4-5. However, humoral and polyfunctional T-cell responses hold higher against WT than BA.4-5 both before and after the booster, suggesting immune imprinting to the wild-type strain. By showing a strengthened antigen-specific immune response, our data reinforce the importance of a variant-adapted mRNA boosters in PWH, possibly directed against the dominant variants alone to maximize the response to circulating strains.
