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 understood. We measured circulating antibodies against the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein, ACE2 displacement and live viral neutralization activities one month following the first and second COVID-19 vaccine doses 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/mm ³ . Nadir CD4+ T-cell counts ranged as low as <10 (median 280; IQR 120-490) cells/mm ³ . After adjustment for sociodemographic, health and vaccine-related variables, HIV infection was significantly associated with 0.2 log ₁₀ lower anti-RBD antibody concentrations (p=0.03) and ∼11% lower ACE2 displacement activity (p=0.02), but not lower viral neutralization (p=0.1) after one vaccine dose. Following two doses however, HIV was no longer significantly associated with the magnitude of any response measured. Rather, older age, a higher burden of chronic health conditions, and having received two ChAdOx1 doses (versus a heterologous or dual mRNA vaccine regimen) were independently associated with lower responses. After two vaccine doses, no significant correlation was observed between the most recent or nadir CD4+ T-cell counts and vaccine responses in PLWH. These results suggest that PLWH with well-controlled viral loads on antiretroviral therapy and CD4+ T-cell counts in a healthy range will generally not require a third COVID-19 vaccine dose as part of their initial immunization series, though other factors such as older age, co-morbidities, vaccine regimen type, and durability of vaccine responses will influence when this group may benefit from additional doses. Further studies of PLWH who are not receiving antiretroviral treatment and/or who have low CD4+ T-cell counts are needed.

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

Panel A: Binding antibody responses to the SARS-CoV-2 spike RBD in serum following one dose of a COVID-19 vaccine 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 colored as above. 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. LLOD: lower limit of detection. ULOQ: upper limit of quantification. Panel B: Binding antibody responses after two vaccine doses, colored as in A. Panel C: Correlation between most recent CD4+ T-cell count and binding antibody responses after one dose (red circles) and two doses (blue circles). Dotted lines are to help visualize the trend.

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

Panel A: ACE2 displacement activities of plasma antibodies following one dose of a COVID-19 vaccine in PLWH (black circles) and controls (grey circles) who were COVID-19 naive at study entry. Convalescent participants (those with anti-N antibodies at study entry) are colored as above. Red bars and whiskers represent median and IQR. Grey shaded area denotes the approximate range of values observed in pre-vaccine plasma from COVID-19 naive participants (see Supplemental Figure 1). P-values were computed using the Mann-Whitney U-test and are uncorrected for multiple comparisons. Panel B: ACE2 displacement activities after two vaccine doses, colored as in A. Panel C: Correlation between most recent CD4+ T-cell count and ACE2 displacement activities after one dose (red circles) and two doses (blue circles). Dotted lines are to help visualize the trend.

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

Panel A: Viral neutralization activities, defined as the lowest reciprocal plasma dilution at which neutralization was observed in all triplicate assay wells, following one dose of a COVID-19 vaccine in PLWH (black circles) and controls (grey circles) who were COVID-19 naive at study entry. Convalescent participants (those with anti-N antibodies at study entry, are colored as above. Red bars and whiskers represent median and IQR. P-values were computed using the Mann-Whitney U-test and are uncorrected for multiple comparisons. LLOD: assay lower limit of detection. ULOQ: assay upper limit of quantification. Panel B: Viral neutralization activities after two vaccine doses, colored as in A. Panel C: Correlation between most recent CD4+ T-cell count and viral neutralization activities after one dose (red circles) and two doses (blue circles). Dotted lines are to help visualize the trend.

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

Panel 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 after one vaccine dose. Data are shown as violin plots with horizontal red lines depicting the mean, 1st and 3rd quartiles. P-values were computed using the Wilcoxon matched-pairs signed rank test, and are uncorrected for multiple comparisons. Panel B: Same as panel A, but for responses after two vaccine doses.