People with HIV receiving suppressive antiretroviral therapy show typical antibody durability after dual COVID-19 vaccination, and strong third dose responses

Abstract

Background: Longer-term humoral responses to two-dose COVID-19 vaccines remain incompletely characterized in people living with HIV (PLWH), as do initial responses to a third dose.

Methods: We measured antibodies against the SARS-CoV-2 spike protein receptor-binding domain, ACE2 displacement and viral neutralization against wild-type and Omicron strains up to six months following two-dose vaccination, and one month following the third dose, in 99 PLWH receiving suppressive antiretroviral therapy, and 152 controls.

Results: Though humoral responses naturally decline following two-dose vaccination, we found no evidence of lower antibody concentrations nor faster rates of antibody decline in PLWH compared to controls after accounting for sociodemographic, health and vaccine-related factors. We also found no evidence of poorer viral neutralization in PLWH after two doses, nor evidence that a low nadir CD4+ T-cell count compromised responses. Post-third-dose humoral responses substantially exceeded post-second-dose levels, though anti-Omicron responses were consistently weaker than against wild-type.Nevertheless, post-third-dose responses in PLWH were comparable to or higher than controls. An mRNA-1273 third dose was the strongest consistent correlate of higher post-third-dose responses.

Conclusion: PLWH receiving suppressive antiretroviral therapy mount strong antibody responses after two- and three-dose COVID-19 vaccination. Results underscore the immune benefits of third doses in light of Omicron.

Figure 1.. Concentrations of total binding antibodies in serum to spike RBD following two and three COVID-19 vaccine doses.

Panel A: Binding antibody responses to the SARS-CoV-2 spike RBD in serum at one, three and six months following the second dose, and one month following the third vaccine dose, in PLWH (orange) and controls (blue) who were COVID-19 naive at the studied time point, as well as individuals who had recovered from COVID-19 at the studied time point (COVID group, black). Participants who experienced a post-vaccination infection were relocated from their original group into the COVID group at their first post-infection study visit, where they are denoted by a red symbol. Participant Ns are shown at the bottom of the plot. The thick horizontal red bar represents the median; thinner horizontal red bars represent the IQR. P-values were computed using the Mann-Whitney U-test (for comparisons between groups) or the Wilcoxon matched pairs test (for comparisons across time points within a group) and are uncorrected for multiple comparisons. ULOQ: upper limit of quantification; LLOD: lower limit of detection. Panel B: Temporal declines in serum binding antibody responses to spike-RBD following two vaccine doses in PLWH (orange) and controls (blue) who remained COVID-19 naive during this period. Only participants with a complete longitudinal data series with no values above the ULOQ are shown. Panel C: Binding antibody half-lives following two COVID-19 vaccine doses, calculated by fitting an exponential curve to the data shown in panel B. Ns are indicated at the bottom of the plot. Red bars and whiskers represent the median and IQR. P-value computed using the Mann Whitney U-test.

Figure 2.. Live virus neutralization activities following two and three COVID-19 vaccine doses.

Viral neutralization activity in plasma at one, three and six months following the second dose, and one month following the third vaccine dose, in PLWH (orange) and controls (blue) who were COVID-19 naive at the studied time point, as well as individuals who had recovered from COVID-19 at the studied time point (COVID group, black). Plasma neutralization was defined as the reciprocal of the highest plasma dilution at which vial cytopathic effect was prevented in all triplicate assay wells. Plasma samples showing neutralization in fewer than three wells at the lowest plasma dilution of 1/20 were coded as having a reciprocal dilution of 10, corresponding to the lower limit of quantification (LLOQ) in this assay. The highest dilution tested was 1/2560, which corresponds to the upper limit of quantification (ULOQ). Participants who experienced a post-vaccination infection were relocated from their original group into the COVID19 group at their first post-infection study visit, where they are denoted by a red symbol. Participant Ns are shown at the bottom of the plot. The thick horizontal red bar represents the median; thinner horizontal red bars represent the IQR. P-values were computed using the Mann-Whitney U-test (for comparisons between groups) or the Wilcoxon matched pairs test (for comparisons across time points within a group) and are uncorrected for multiple comparisons.

Figure 3:. Anti-Omicron IgG binding and ACE2 displacement activities one month after the second and third COVID-19 vaccine doses.

Panel A: Binding IgG responses in plasma to the wild-type (WT) and Omicron (OM) spike-RBD (S-RBD), measured using the Meso Scale Diagnostics V-Plex assay, in PLWH (orange) and controls (blue) who remained COVID-19 naive throughout the study. Participant Ns are shown at the bottom of the plot. Thick horizontal red bar represents the median; thinner horizontal red bars represent the IQR. P-values were computed using the Wilcoxon matched pairs test (for all within-group comparisons) or the Mann-Whitney U-test (for between-group comparisons) and are uncorrected for multiple comparisons. Panel B: same as A, but for ACE2 displacement activity, measured using the V-plex SARS-CoV-2 (ACE2) assay, where results are reported in terms of % ACE2 displacement.

Figure 4:. Anti-Omicron neutralization activities one month after the second and third COVID-19 vaccine doses.

Neutralization activities, reported as the reciprocal of the highest plasma dilution at which neutralization was observed in all triplicate assay wells, against the wild-type (WT) and Omicron (OM) virus isolates a subset of PLWH (orange) and controls (blue) who remained COVID-19 naive throughout the study. Participant Ns are shown at the bottom of the plot. Thick horizontal red bar represents the median; thinner horizontal red bars represent the IQR. P-values were computed using the Wilcoxon matched pairs test (for within-group comparisons) or the Mann-Whitney U-test (for between-group comparisons) and are uncorrected for multiple comparisons.