Limited Humoral and Specific T-Cell Responses After SARS-CoV-2 Vaccination in PWH With Poor Immune Reconstitution

Abstract

Background We analyzed humoral and cellular immune responses induced by SARS-CoV-2 mRNA vaccines in people living with HIV-1 (PLWH) with < 200 CD4+ T-cells. Methods Prospective cohort study including 58 PLWH with CD4+ T-cell counts <200 cells/mm3, 36 with CD4+ T-cell counts >500, and 33 HIV-1-negative controls. Antibodies against the SARS-CoV-2 Spike protein (anti-S IgG) and the receptor-binding domain (anti-RBD IgG) were quantified before and four weeks after the first and the second dose of BNT162b2 or mRNA-1273 (w8). Viral neutralization activity and T-cell responses were also determined. Results At w8, anti-S/anti-RBD IgG responses increased in all groups (P < 0.0001). Median (IQR) S-IgG and RBD-IgG at w8 were 153.6 (26.4; 654.9) and 171.9 (61.8; 425.8) in the HIV < 200 group compared to 245.6 (145; 824) and 555.8 (166.4; 1751) in the HIV > 500 group, and 274.7 (193.7; 680.4) and 281.6 (181; 831.8) BAU/mL in controls (P < 0.05). Neutralizing capacity and specific T-cell immune responses were absent or reduced in 33% of the HIV < 200 group, compared with 3.7% in the HIV > 500 (P = 0.0003). Conclusion One third of PLWH with CD4+ T-cell counts <200 cells/mm3 show low anti-S/anti-RBD IgG levels, reduced in vitro neutralization activity against SARS-CoV-2 and no vaccine-induced T-cells after receiving COVID-19 mRNA vaccines.

SARS-CoV-2-Specific T Cell Responses in Immunocompromised Individuals with Cancer, HIV or Solid Organ Transplants

“…Accordingly, after adjustment for major confounders (e.g., age, CD4+ nadir, or years since HIV diagnosis), a low CD4+ T cell count was linked to significantly impaired humoral and cellular immune responses after SARS-CoV-2 mRNA vaccination ( Figure 4 B) [ 133 ]. Further support for these results is delivered by additional studies with similar approaches considering the effect of a low CD4+ T cell count on the vaccination success in PLWH [ 134 , 135 ].…”

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

“…On the contrary, PLWH with low CD4 + T-cell counts, detectable viremia, and/or previous AIDS were found to have weaker and less durable humoral and T-cell responses to mRNA vaccines [ 95 •, 96 ••, 98 •, 99 , 100 , 101 •], suggesting that they may benefit from additional vaccine doses. In this respect, a third dose of a mRNA vaccine following the primary cycle has been shown to strongly boost humoral albeit not T-cell responses in PLWH with advanced disease at the time of HIV diagnosis (CD4 + T-cells < 200/μL and/or AIDS), irrespective of the current CD4 + T-cell count [ 102 ••].…”

“…[ 118 ] BNT162b or mRNA-1273 (2 doses) Observational cohort study (Switzerland) 333 PLWH: 65 (20.2%) females; age > 60 years: n = 231 (72%) CD4 + T-cell counts > 350/μL: n = 298 (92.8%) HIV-RNA < 50 copies/mL: n = 13 (4%) Individuals with prior SARS-CoV-2 infection excluded Antibody response to SARS-CoV-2 [Antibody Coronavirus Assay 2 (ABCORA 2), which also allows for a reliable prediction of neutralization activity against the SARS-CoV-2 Wuhan-Hu-1 strain based on anti-S1 reactivity] Antibody response higher among PLWH < 60 years, with CD4 + cell count > 350 cells/mL and vaccinated with mRNA-1273 compared with BNT162b2 Pre-infection with SARS-CoV-2 boosted the antibody response Benet et al . [ 101 •] BNT162b2 or mRNA-1273 (2 doses) Prospective observational single-center cohort study (Spain) 94 PLWH, described according to CD4 + T-cell count strata: < 200/μL: 79.3% males; median age: 52 years (IQR: 40–56) > 500/μL: 80.6% males; median age: 51 years (IQR: 40–56) 33 HIV-negative controls: 18 (54.5%) males; median age: 53 years (IQR: 35–57) CD4 + T-cell strata: - < 200/μL: n = 58 - > 500/μL: n = 36 Undetectable plasma HIV-RNA: - CD4 + < 200/μL group: n = 47 (81%) - CD4 + > 500/μL group: n = 35 (100%) Individuals with known history of SARS-CoV-2 infection excluded Anti-S IgG and anti-RBD IgG (ELISA) Neutralizing antibody activity (neutralization assay) SARS-CoV-2 specific T-cells (ELISpot after stimulation of PBMCs with a pool of overlapping SARS-CoV-2 peptides) Lower anti-S and anti-RBD IgG levels in PLWH with CD4 + T-cell counts < 200/μL Neutralizing capacity and specific T-cell responses (against wild-type SARS-CoV-2 and VOCs like Alpha, Delta, Kappa) absent or reduced in a higher percentage of PLWH with CD4 + T-cell counts < 200/μL Woldemeskel et al . [ 123 •] PLWH: BNT162b2 (2 doses) HIV-negative controls: mRNA-1273 (2 doses) Prospective observational study (USA) 8 PLWH: age range: 41–60 years 25 HIV-negative controls: age range: 21–60 years Median CD4 + T-cell count: 1044/μL (IQR: 468–1420) All PLWH on cART 6 PLWH had plasma HIV-RNA < 20 copies/mL, while 2 PPLWH had low level viremia (49 and 52 copies/mL, respectively) Not part of study criteria Anti-S1 IgG (ELISA) ACE2-inhibiting antibodies (...…”

Humoral Response after Two Doses of BNT162b2 mRNA Vaccine Has a Role in Predicting Response after Three Doses That Is Related to Plasma HIV Viremia and Nadir CD4+ Cell Count in HIV-Positive Patients

“…The overall CD4+ cell did not influence evolution of humoral response from T2 to T3. The CD4+ cell count reflects the immunocompetence level [ 32 ], and the median value was higher than 500 cells/mm 3 in all patients except for those with a low response, and at least one HIV RNA plasma value of >20 copies/mL (OV); however, they had a median value of 427 cells/mm 3 , which is more than double the threshold of 200 CD4+ cells/mm 3 associated with a low humoral response to the COVID-19 vaccine [ 31 , 33 ].…”