SARS-CoV-2 vaccine booster in solid organ transplant recipients previously immunised with inactivated versus mRNA vaccines: A prospective cohort study

Abstract

Background: Solid-organ transplant (SOT) recipients have worse COVID-19 outcomes than general population and effective immunisation in these patients is essential but more difficult to reach. We aimed to determine the immunogenicity of an mRNA SARS-CoV-2 vaccine booster in SOT recipients previously immunised with either inactivated or homologous SARS-CoV-2 mRNA vaccine.

Methods: Prospective cohort study of SOT recipients under medical care at Red de Salud UC-CHRISTUS, Chile, previously vaccinated with either CoronaVac or BNT162b2. All participants received a BNT162b2 vaccine booster. The primary study end point was anti-SARS-CoV-2 total IgG antibodies (TAb) seropositivity at 8-12 weeks (56-84 days) post booster. Secondary end points included neutralising antibodies (NAb) and specific T-cell responses.

Findings: A total of 140 (50% kidney, 38% liver, 6% heart) SOT recipients (mean age 54 [13.6] years; 64 [46%] women) were included. Of them, 62 had homologous (three doses of BNT162b2) and 78 heterologous vaccine schedules (two doses of CoronaVac followed by BNT162b2 booster). Boosters were received at a median of 21.3 weeks after primary vaccination. The proportion achieving TAb seropositivity (82.3% vs 65.4%, P = 0.035) and NAb positivity (77.4% vs 55.1%, P = 0.007) were higher for the homologous versus the heterologous group. On the other hand, the number of IFN-γ and IL-2 secreting SARS-CoV-2-specific T-cells did not differ significantly between groups.

Interpretation: This cohort study shows that homologous mRNA vaccine priming plus boosting in SOT recipients, reaches a significantly higher humoral immune response than inactivated SARS-CoV-2 vaccine priming followed by heterologous mRNA booster.

Funding: School of Medicine, UC-Chile and ANID.ClinicalTrials.gov ID: NCT05124509.

Keywords: BNT162b2; COVID-19; CoronaVac; SARS-CoV-2; Solid organ transplant; Vaccine; Vaccine immunogenicity.

Conflict of interest statement

S.M.B., N.L.C. and A.K. reported having participated as leading scientists for design of CoronaVac clinical trials sponsored in Chile by Pontificia Universidad Católica de Chile and in collaboration with Sinovac Biotech (NCT04651790 and NCT04992260).

© 2022 The Author(s).

Figures

Figure 1

Study flow-chart. Adult solid organ recipients transplanted within 10 years prior to study initiation, under medical care at the Transplant Institute, Red de Salud UC CHRISTUS.

Figure 2

Humoral response against SARS-CoV-2 in SOT recipients with an homologous or heterologous vaccination schedule. Serum was obtained between 8-12 weeks after the mRNA vaccine in the homologous group (n = 62) and the heterologous group (n = 78). Distribution for (a) frequency of total IgG (TAb) anti-S1 positivity (≥11 relative units per ml, RU/ml), (b) total IgG anti-S1 geometric mean concentration (GMC) (95%CI), RU/ml), (c) neutralising antibodies (NAb) positivity (≥30% of inhibition rate) and (d) neutralising activity (median (IQR) of percentage of inhibition). Dotted line in (b) and (d) show seropositivity cut-off. Statistical significance was calculated with Fisher test (a,c), Mann-Whitney (b,d); two-tailed P values are shown.

Figure 3

Evaluation of IFN-γ and IL-2 secreting Spot Forming T cells in SOT recipients with homologous and heterologous vaccination schedules. PBMCs (3×105 cells) obtained between 8-12 weeks after mRNA vaccine in the homologous group (n = 29) and the heterologous group (n = 31) were stimulated with megapool of peptides (MP S-R), or megapool of peptides (MP CD8) from SARS-CoV-2 proteins. (a) IFN-γ-secreting spot forming T cells (SFC) and (b) IL-2-secreting SFC were quantified by ELISPOT. Medians and interquartile ranges are shown. Statistical significance was calculated with Mann-Whitney test.