Antibody and T-Cell Response to Bivalent Booster SARS-CoV-2 Vaccines in People With Compromised Immune Function: COVERALL-3 Study

Abstract

Background: Bivalent messenger RNA (mRNA) vaccines, designed to combat emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, incorporate ancestral strains and a new variant. Our study assessed the immune response in previously vaccinated individuals of the Swiss HIV Cohort Study (SHCS) and the Swiss Transplant Cohort Study (STCS) following bivalent mRNA vaccination.

Methods: Eligible SHCS and STCS participants received approved bivalent mRNA SARS-CoV-2 vaccines (mRNA-1273.214 or BA.1-adapted BNT162b2) within clinical routine. Blood samples were collected at baseline, 4 weeks, 8 weeks, and 6 months postvaccination. We analyzed the proportion of participants with anti-spike protein antibody response ≥1642 units/mL (indicating protection against SARS-CoV-2 infection), and in a subsample T-cell response (including mean concentrations), stratifying results by cohorts and population characteristics.

Results: In SHCS participants, baseline anti-spike antibody concentrations ≥1642 units/mL were observed in 87% (96/112), reaching nearly 100% at follow-ups. Among STCS participants, 58% (35/60) had baseline antibodies ≥1642 units/mL, increasing to 80% at 6 months. Except for lung transplant recipients, all participants showed a 5-fold increase in geometric mean antibody concentrations at 4 weeks and a reduction by half at 6 months. At baseline, T-cell responses were positive in 96% (26/27) of SHCS participants and 36% (16/45) of STCS participants (moderate increase to 53% at 6 months). Few participants reported SARS-CoV-2 infections, side-effects, or serious adverse events.

Conclusions: Bivalent mRNA vaccination elicited a robust humoral response in individuals with human immunodeficiency virus (HIV) or solid organ transplants, with delayed responses in lung transplant recipients. Despite a waning effect, antibody levels remained high at 6 months and adverse events were rare. Clinical Trials Registration . NCT04805125.

Keywords: HIV; SARS-CoV-2; bivalent vaccine; organ transplant; vaccine.

Figure 1.

Antibody concentrations before and after vaccination with bivalent mRNA SARS-CoV-2 vaccines in PWH (stratified by CD4 cell counts below and above 350 cells/µL) and solid organ transplant recipient (stratified by kidney and lung recipients), measured with the Elecsys Anti-SARS-CoV-2 S assay. Red dots indicate mean values; boxplots indicate median and interquartile range, whiskers indicate minimum and maximum (excluding outliers). The University Hospital Basel center did not perform reruns with further dilutions if the antibody concentrations were >2500 units/mL. Hence, in order not to distort the results, all samples from the University Hospital of Basel were excluded. Abbreviations: mRNA, messenger RNA; PWH, people with human immunodeficiency virus; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.

Figure 2.

T-cell geometric mean concentration before and after vaccination with bivalent mRNA SARS-CoV-2 vaccines in PWH (stratified by CD4 cell counts below and above 350 cells/µL) and solid organ transplant recipients (stratified by kidney and lung recipients), measured with the interferon-γ release assay. Red dots indicate mean values, boxplots indicate median and interquartile range; whiskers indicate minimum and maximum (excluding outliers). Participants with a nonevaluable T-cell response were excluded. Abbreviations: mRNA, messenger RNA; PWH, people with human immunodeficiency virus; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.