Quality of T-Cell Response to SARS-CoV-2 mRNA Vaccine in ART-Treated PLWH

Abstract

We investigated specific humoral and T-cell responses in people living with HIV (PLWH) before (T0), after two (T1) and after six months (T2) from the third dose of the BNT162b2 vaccine. Healthy donors (HD) were enrolled. The specific humoral response was present in most PLWH already after the second dose, but the third dose increased both the rate of response and its magnitude. Collectively, no significant differences were found in the percentage of responding T-cells between PLWH and HD. At T0, stratifying PLWH according to CD4 cell count, a lower percentage of responding T-cells in <200 cells/µL subgroup compared to >200 cells/µL one was observed. At T1, this parameter was comparable between the two subgroups, and the same result was found at T2. However, the pattern of co-expression of IFNγ, IL2 and TNFα in PLWH was characterized by a higher expression of TNFα, independently of CD4 cell count, indicating a persistent immunological signature despite successful ART. mRNA vaccination elicited a specific response in most PLWH, although the cellular one seems qualitatively inferior compared to HD. Therefore, an understanding of the T-cell quality dynamic is needed to determine the best vaccination strategy and, in general, the capability of immune response in ART-treated PLWH.

Immune responses to mRNA‐based vaccines given as a third COVID‐19 vaccine dose in people living with HIV—a literature review

“…The initial search produced 772 articles, of which 323 were duplicate publications. Eight of the 449 remaining articles included studies involving measurements on the humoral immunity against SARS-CoV-2 in PLWH after a third dose of an mRNA-based COVID-19 vaccine and were eligible for inclusion in this study (9)(10)(11)(12)(13)(14)(15)(16). Five of the studies also investigated the cellular immunity (11,(13)(14)(15)(16).…”

“…Eight of the 449 remaining articles included studies involving measurements on the humoral immunity against SARS-CoV-2 in PLWH after a third dose of an mRNA-based COVID-19 vaccine and were eligible for inclusion in this study (9)(10)(11)(12)(13)(14)(15)(16). Five of the studies also investigated the cellular immunity (11,(13)(14)(15)(16). Out of the eight included studies, five were case-control studies (10)(11)(12)(13)(14) and three were case studies (9,15,16).…”

“…Five of the studies also investigated the cellular immunity (11,(13)(14)(15)(16). Out of the eight included studies, five were case-control studies (10)(11)(12)(13)(14) and three were case studies (9,15,16). A brief overview of patient and control group characteristics including HIVrelated health variables for each patient group is shown in Tables 1 and 2.…”

“…Antibodies targeting S antigen were measured in seven of the eight studies who all found a significant increase in antibody levels after the third dose compared with the second dose (9)(10)(11)(13)(14)(15)(16).…”

SARS-CoV-2 Neutralizing Antibodies to B.1 and to BA.5 Variant after Booster Dose of BNT162b2 Vaccine in HIV Patients COVID-Naïve and on Successful Antiretroviral Therapy

“…In HIV-positive patients, the influence of viroimmunological parameters had to be taken into account: most subjects on successful ART with a high CD4+ cell count at inclusion and receiving two doses of the BNT162b2 vaccine had a cellular response after six months, and a high number of CD4+ cell count is a predicting factor [10]. A comparable T cell response after six months from the third dose of the BNT162b2 vaccine was described in patients with either less or more than 200 cells/mm 3 , but with virological suppression (median HIV RNA 40 copies/mL) [11]. These results suggest that a standard vaccine schedule could be applied to HIV patients with ongoing successful ART, but untreated or failed subjects may need a tailored vaccine administration.…”