Long-term quantitative assessment of anti-SARS-CoV-2 spike protein immunogenicity (QUASI) after COVID-19 vaccination in older people living with HIV (PWH)

Abstract

Background The durability of immune responses to COVID-19 vaccines among older people living with HIV (PWH) is clinically important. Methods We aimed to assess vaccine-induced humoral immunity and durability in older PWH (≥ 55 years, n = 26) over 6 months (post-initial BNT162b2 series). A secondary and exploratory objective was to assess T-cell response and BNT162b2 booster reactogenicity, respectively. Our Visit 1 (3 weeks post-initial BNT162b2 dose) SARS-CoV-2 humoral immunity results are previously reported; these subjects were recruited for Visit 2 [2 weeks (+ 1 week window) post-second vaccination] and Visit 3 [6 months (± 2 week window) post-initial vaccination] in a single-center longitudinal observational study. Twelve participants had paired Visit 2/3 SARS-CoV-2 Anti-Spike IgG data. At Visit 3, SARS-CoV-2 Anti-Spike IgG testing occurred, and 5 subjects underwent T-cell immune response evaluation. Thereafter, subjects were offered BNT162b2 booster (concurrent day outside our study) per US FDA/CDC guidance; reactogenicity was assessed. The primary study outcome was presence of detectable Visit 3 SARS-CoV-2 Anti-Spike-1-RBD IgG levels. Secondary and exploratory outcomes were T-cell immune response and BNT162b2 booster reactogenicity, respectively. Wilcoxon signed-rank tests analyzed median SARS-CoV-2 Anti-Spike IgG 6-month trends. Results At Visit 3, 26 subjects underwent primary analysis with demographics noted: Median age 61 years; male n = 16 (62%), female n = 10 (38%); Black n = 13 (50%), White n = 13 (50%). Most subjects (n = 20, 77%) had suppressed HIV viremia on antiretroviral therapy, majority (n = 24, 92%) with CD4 > 200 cells/µL. At Visit 3, 26/26 (100%) had detectable Anti-Spike-1-RBD (≥ 0.8 U/mL). Among 12 subjects presenting to Visit 2/3, median SARS-CoV-2 Anti-Spike 1-RBD was 2087 U/mL at Visit 2, falling to 581.5 U/mL at Visit 3 (p = 0.0923), with a median 3.305-fold decrease over 6 months. Among subjects (n = 5) with 6-month T-cell responses measured, all had detectable cytokine-secreting anti-spike CD4 responses; 3 had detectable CD4 + Activation induced marker (AIM) + cells. Two had detectable cytokine-secreting CD8 responses, but all had positive CD8 + AIM + cells. Conclusions Among older PWH, SARS-CoV-2 Anti-Spike IgG and virus-specific T-cell responses are present 6 months post-primary BNT162b2 vaccination, and although waning, suggest retention of some degree of long-term protective immunity.

Long Term Assessment of Anti-SARS-CoV-2 Immunogenicity after mRNA Vaccine in Persons Living with HIV

“…Waning immunity, also after a booster dose, has been associated with increased vulnerability to SARS-CoV-2 infection/reinfection, particularly in case of immune-evasive VOCs [ 33 , 34 , 35 ]. Our results are consistent with other reports that showed a similar decay of humoral immune responses after six months in PLWH with high CD4 count and in healthy donors following SARS-CoV-2 vaccinations [ 18 , 19 , 27 , 36 ], but the peculiarity of this work is the inclusion of participants with CD4 count <500 cells/mm 3 . Of note, responses in this latter group appear to be similar to those seen in the general population.…”

“…Nonetheless, memory B- and T cells—which modulate adaptive immune responses, serve as a tool of defense against disease severity and may exhibit greater durability [ 38 ] and this is why a lot of attention has been given to cell-mediated immune responses post-COVID-19 vaccination. Although T cell responses were previously evaluated only in small studies, persistent spike-specific T cells six-months post-primary mRNA vaccination were found among older PLWH [ 36 ], a response which retained activity against viral mutations [ 9 ]. In our study, IFN-γ production, which was used as a surrogate of T specific cell immunity, was lower in the LCD4 compared to the other groups but remained stable over time and above the threshold of suboptimal response regardless of CD4 count.…”

The effect of HIV on COVID-19 vaccine responses

“…Six months post two dose vaccination, all individuals had detectable anti-Spike-1-RBD antibody with a median of 3.3-fold decrease over 6 months. T-cell responses measured after 6 months were still detectable [32].…”

Immunologic Interplay Between HIV/AIDS and COVID-19: Adding Fuel to the Flames?

“…[ 97 ] BNT162b2 (2 doses) Observational study (USA) 12 PLWH: 5 males, 7 females; median age: 52 years (IQR: 25–59) 17 HIV-negative controls: 10 males, 7 females; median age: 41 years (IQR: 24–59) Median CD4 + T-cell count: 913/μL (IQR: 649–1678) Plasma HIV-RNA > 20 copies/mL in 3 individuals despite cART No evidence of prior SARS-CoV-2 infection by history or serology Anti-S1 IgG (ELISA) ACE2 blocking activity (spike-ACE2 binding inhibition assay) SARS-CoV-2–specific T-cell response (IFN-γ ELISpot after stimulation of PBMCs with a pool of overlapping SARS-CoV-2 spike protein peptides) Comparable humoral and T-cell responses in PLWH and HIV-negative controls Higher antibody titers in women compared to men Tuan et al . [ 124 ] BNT162b2 (2 doses) Observation cohort study (USA) 26 PLWH: 16 (62%) males, 10 (38%) females; median age: 61 years CD4 T-cell count > 200/μL: 24 (92%) Plasma HIV-RNA: - undetectable: n = 20 - detectable < 100 copies/mL: n = 6 Individuals with prior laboratory-confirmed or breakthrough COVID-19 excluded Anti-RBD IgG (ELISA) SARS‑CoV‑2–specific T-cells (intracellular cytokine staining (ICS) assay and activation induced marker (AIM) assay by flow cytometry after stimulation of PBMCs with a pool of overlapping SARS-CoV-2 spike protein peptides) Time-points: 3 weeks post first vaccination; 2 weeks post second vaccination; 6 months post-first vaccination Anti-RBD IgG detectable in 100% PLWH with a median 3.305-fold decrease 6 months after vaccination SARS-CoV-2–specific T-cell responses also present 6 months after primary vaccination Sisteré-Oró et al . [ 98 •] BNT162b2 (2 doses) Observational study (Spain) 10 immunological non-responder (INR) PLWH: 7 (70%) males; median age: 49 years (IQR: 30–71) 10 HIV-negative controls: 4 (40%) males; median age: 47 years (IQR: 26–72) CD4 + T-cell count strata: - < 200/μL: n = 8 (80%) - 200–349: n = 2 (20%) All PLWH on ART for ≥ 6 months Undetectable plasma HIV-RNA: n = 8 (80%) No evidence of prior SARS-CoV-2 infection Anti-S IgG (ELISA) Neutralizing antibody activity (NeutraLISA assay) SARS-CoV-2–specific T-cells (ELISpot after stimulation of PBMCs with a pool of overlapping SARS-CoV-2 spike protein peptides) Time-points: pre-vaccination, post-vaccination, and 3 weeks after an additional boost in 3 previous non-r...…”