Humoral and cellular immune responses eleven months after the third dose of BNT162b2 an mRNA-based COVID-19 vaccine in people with HIV - a prospective observational cohort study

Abstract

Background: We investigated long-term durability of humoral and cellular immune responses to third dose of BNT162b2 in people with HIV (PWH) and controls.

Methods: In 378 PWH with undetectable viral replication and 224 matched controls vaccinated with three doses of BNT162b2, we measured IgG-antibodies against the receptor binding domain of SARS-CoV-2 spike protein three months before third dose of BNT162b2, and four and eleven months after. In 178 PWH and 135 controls, the cellular response was assessed by interferon-γ (IFN-γ) release in whole blood four months after third dose. Differences in antibody or IFN-γ concentrations were assessed by uni- and multivariable linear regressions.

Findings: Before the third dose the concentration of SARS-CoV-2 antibodies was lower in PWH than in controls (unadjusted geometric mean ratio (GMR): 0.68 (95% CI: 0.54-0.86, p = 0.002). We observed no differences in antibody concentrations between PWH and controls after four (0.90 (95% CI: 0.75-1.09), p = 0.285) or eleven months (0.89 (95% CI: 0.69-1.14), p = 0.346) after the third dose. We found no difference in IFN-γ concentrations four months after the third dose between PWH and controls (1.06 (95% CI: 0.71-1.60), p = 0.767).

Interpretation: We found no differences in antibody concentrations or cellular response between PWH and controls up to eleven months after third dose of BNT162b2. Our findings indicate that PWH with undetectable viral replication and controls have comparable immune responses to three doses of the BNT162b2 vaccine.

Funding: This work was funded by the Novo Nordisk Foundation (NFF205A0063505, NNF20SA0064201), the Carlsberg Foundation (CF20-476 0045), the Svend Andersen Research Foundation (SARF2021), and Bio- and Genome Bank Denmark.

Keywords: BNT162b2; Booster dose; HIV; Immune response; SARS-CoV-2.

Fig. 1

Observed anti-RBD IgG concentrations and geometric mean concentrations of anti-RBD IgG up to one year after the third BNT162b2 vaccination in people with HIV (PWH) and controls. The figure shows the geometric mean concentration (GMC) of anti-RBD IgG predicted by linear regression in AU/mL on a log₁₀ scale plotted on top of observed individual concentrations of anti-RBD IgG from PWH in blue triangles and controls in red circles. The dotted horizontal lines indicate the minimum threshold of an IgG response. Error bars indicate 95% confidence intervals. a) Composite predicted anti-RBD IgG GMC irrespective of previous infection status in PWH (blue) and controls (red). b) Predicted geometric mean concentrations of SARS-CoV-2 antibodies stratified by the presence of antibodies targeting the nucleocapsid protein as indication of a previous infection in PWH (blue) and controls (red). Solid line and filled circles/triangles indicate presence of N-antibodies. Dotted line and open circles/triangles indicate that N-antibodies were not detected.