Humoral immune responses to COVID-19 vaccination in people living with HIV receiving suppressive antiretroviral therapy

Abstract

Humoral responses to COVID-19 vaccines in people living with HIV (PLWH) remain incompletely characterized. We measured circulating antibodies against the SARS-CoV-2 spike protein receptor-binding domain (RBD), ACE2 displacement and viral neutralization activities one month following the first and second COVID-19 vaccine doses, and again 3 months following the second dose, in 100 adult PLWH and 152 controls. All PLWH were receiving suppressive antiretroviral therapy, with median CD4+ T-cell counts of 710 (IQR 525-935) cells/mm³, though nadir CD4+ T-cell counts ranged as low as <10 cells/mm³. After adjustment for sociodemographic, health and vaccine-related variables, HIV infection was associated with lower anti-RBD antibody concentrations and ACE2 displacement activity after one vaccine dose. Following two doses however, HIV was not significantly associated with the magnitude of any humoral response after multivariable adjustment. Rather, older age, a higher burden of chronic health conditions, and dual ChAdOx1 vaccination were associated with lower responses after two vaccine doses. No significant correlation was observed between recent or nadir CD4+ T-cell counts and responses to two vaccine doses in PLWH. These results indicate that PLWH with well-controlled viral loads and CD4+ T-cell counts in a healthy range generally mount strong initial humoral responses to dual COVID-19 vaccination. Factors including age, co-morbidities, vaccine brand, response durability and the rise of new SARS-CoV-2 variants will influence when PLWH will benefit from additional doses. Further studies of PLWH who are not receiving antiretroviral treatment or who have low CD4+ T-cell counts are needed, as are longer-term assessments of response durability.

Fig. 1. Binding antibody responses to spike RBD following one and two COVID-19 vaccine doses.

a Binding antibody responses to the SARS-CoV-2 spike RBD in serum one month following the first COVID-19 vaccine dose in PLWH (black circles) and controls (grey circles) who were COVID-19 naive at study entry. Convalescent participants, denoting those with anti-N antibodies at study entry, are presented as a single group but colored by subgroup as above. The numbers of participants analyzed are indicated at the bottom of the plot. Red bars and whiskers represent the median and IQR. p-values were computed using the Mann–Whitney U-test and are uncorrected for multiple comparisons. U-statistics were 4238 (PLWH naive vs. control naive), 93 (PLWH naive vs. convalescent), and 173 (control naive vs. convalescent). LLOD lower limit of detection, ULOQ upper limit of quantification. b Binding antibody responses one month after the second dose, presented as in (a). U-statistics were 4976 (PLWH naive vs. control naive), 675 (PLWH naive vs. convalescent) and 1226 (control naive vs. convalescent). c Binding antibody responses three months after the second dose, presented as in (a). U-statistics were 3841 (PLWH naive vs. control naive), 539 (PLWH naive vs. convalescent) and 1123 (control naive vs. convalescent). d Binding antibody responses plotted longitudinally for each group, beginning with the pre-vaccine time point. Red dotted lines connect participants’ longitudinal measurements. The numbers of participants analyzed are indicated at the bottom of the plot. e Correlation between most recent CD4+ T-cell count and binding antibody responses one month after the first dose (red circles; n = 90), one month after the second dose (blue circles; n = 91) and three months following the second dose (clear circles; n = 85). Matching-coloured dotted lines help visualize the trend.

Fig. 2. Ability of vaccine-induced antibodies to block ACE2-receptor binding following one and two COVID-19 vaccine doses.

a ACE2 displacement activities of plasma antibodies one month following the first COVID-19 vaccine dose in PLWH (black circles) and controls (grey circles) who were COVID-19 naive at study entry. Convalescent participants are colored by subgroup. The numbers of participants analyzed are indicated at the bottom of the plot. Red bars and whiskers represent median and IQR. Grey shaded area denotes the range of values observed in pre-vaccine plasma from COVID-19 naive participants (see d). p-values were computed using the Mann–Whitney U-test and are uncorrected for multiple comparisons. U-statistics were 4002 (PLWH naive vs. control naive), 144 (PLWH naive vs. convalescent) and 255 (control naive vs. convalescent). b ACE2 displacement activities one month after the second dose, presented as in (a). U-statistics were 5618 (PLWH naive vs. control naive), 660 (PLWH naive vs. convalescent) and 917 (control naive vs. convalescent). c ACE2 displacement activities 3 months after the second dose, presented as in (a). U-statistics were 4353 (PLWH naive vs. control naive), 644 (PLWH naive vs. convalescent) and 839 (control naive vs. convalescent). d ACE2 displacement activities plotted longitudinally for each group. Pre-vaccine measurements were performed only on a subset of COVID-19 naive participants to estimate assay background, shown as grey shading. The numbers of participants analyzed are indicated at the bottom of the plot. Red dotted lines connect participants’ longitudinal measurements. e Correlation between most recent CD4+ T-cell count and ACE2 displacement activities one month after the first dose (red circles; n = 90), one month after the second dose (blue circles; n = 90) and three months following the second dose (clear circles; n = 79). Matching-coloured dotted lines help visualize the trend.

Fig. 3. Ability of vaccine-induced antibodies to neutralize live SARS-CoV-2 following one and two COVID-19 vaccine doses.

a Viral neutralization activities, defined as the highest reciprocal plasma dilution at which neutralization was observed in all triplicate assay wells, one month following the first COVID-19 vaccine dose in PLWH (black circles) and controls (grey circles) who were COVID-19 naive at study entry. Convalescent participants are colored by subgroup. The numbers of participants analyzed are indicated at the bottom of the plot. Red bars and whiskers represent median and IQR. p-values were computed using the Mann–Whitney U-test and are uncorrected for multiple comparisons. U-statistics were 5721 (PLWH naive vs. control naive), 116 (PLWH naive vs. convalescent) and 158 (control naive vs. convalescent). LLOD: assay lower limit of detection. ULOQ: assay upper limit of quantification. b Viral neutralization activities one month after the second vaccine dose, presented as in (a). U-statistics were 5131 (PLWH naive vs. control naive), 664 (PLWH naive vs. convalescent) and 777 (control naive vs. convalescent). c Viral neutralization activities 3 months after the second dose, presented as in (a). U-statistics were 4984 (PLWH naive vs. control naive), 431 (PLWH naive vs. convalescent) and 686 (control naive vs. convalescent). d Viral neutralization activities plotted longitudinally for each group. Pre-vaccine measurements were performed only on a subset of COVID-19 naive and convalescent participants, none of whom had detectable neutralization activity at this time. The numbers of participants analyzed are indicated at the bottom of the plot. Note that many values are superimposed. Red dotted lines connect participants’ longitudinal measurements. e Correlation between most recent CD4+ T-cell count and viral neutralization activities one month after the first dose (red circles, n = 90), one month after the second dose (blue circles, n = 90) and three months following the second dose (clear circles, n = 80). Matching-coloured dotted lines help visualize the trend.

Fig. 4. ACE2 displacement activities against the original and Delta SARS-CoV-2 variants after one and two doses of COVID-19 vaccine.

a ACE2 displacement activities of plasma antibodies against the original wild-type (wt) and Delta variant Spike-RBD in naive PLWH, naive controls, and convalescent individuals one month after the first vaccine dose. Horizontal red lines depict the median, 1st and 3rd quartiles. p-values were computed using the Wilcoxon matched-pairs signed rank test and are uncorrected for multiple comparisons. b Responses one month after the second vaccine dose, displayed as in (a). c Responses 3 months after the second vaccine dose, displayed as in (a).