Immune Response Against Recent Omicron Sub-Lineages in Persons with HIV Receiving a Protein-Based or mRNA XBB.1.5 SARS-CoV-2 Booster Vaccine

The new Nuvaxovid protein-based and Pfizer-BioNTech mRNA-based vaccines targeting Omicron XBB.1.5 were available during the 2023–2024 autumn/winter vaccination campaign for frail individuals, including people with HIV (PWH). We assessed the immune response in 51 PWH on stable ART who received a booster with either the Nuvaxovid protein-based (n = 25) or Pfizer-BioNTech mRNA-based XBB.1.5 vaccine (n = 26). The median age was 57 years (IQR 51–65), the median count of CD4 at T0 was 652/mmc (503–935), and CD4 nadir was 226/mmc (95–340). Samples were collected before (T0) and one month after (T1) the booster. We measured neutralizing antibodies (nAbs) titers against D614G, XBB.1.6, and JN.1 variants and T-cell IFN-γ levels produced upon specific stimulation. Regardless of the vaccine used, we observed a marked increase in nAbs titers from T0 to T1 against all the subvariants, but no evidence for a change in IFN-γ release. After controlling for confounders, there was no evidence for a difference in the T0-T1 change in nAbs titers against XBB.1.16 and JN.1 by the type of vaccine, while Nuvaxovid determined a smaller increase in D614G nAbs (p = 0.008). The XBB.1.5 protein-based vaccine’s immunogenicity as a fifth or later booster was comparable to the Pfizer-BioNTech mRNA vaccine, particularly against recent Omicron variants.