Impaired humoral and cellular response to primary COVID-19 vaccination in patients less than 2 years after allogeneic bone marrow transplant

Abstract

Allogeneic haematopoietic stem cell transplant (HSCT) recipients remain at high risk of adverse outcomes from coronavirus disease 2019 (COVID-19) and emerging variants. The optimal prophylactic vaccine strategy for this cohort is not defined. T cell-mediated immunity is a critical component of graft-versus-tumour effect and in determining vaccine immunogenicity. Using validated anti-spike (S) immunoglobulin G (IgG) and S-specific interferon-gamma enzyme-linked immunospot (IFNγ-ELIspot) assays we analysed response to a two-dose vaccination schedule (either BNT162b2 or ChAdOx1) in 33 HSCT recipients at ≤2 years from transplant, alongside vaccine-matched healthy controls (HCs). After two vaccines, infection-naïve HSCT recipients had a significantly lower rate of seroconversion compared to infection-naïve HCs (25/32 HSCT vs. 39/39 HCs no responders) and had lower S-specific T-cell responses. The HSCT recipients who received BNT162b2 had a higher rate of seroconversion compared to ChAdOx1 (89% vs. 74%) and significantly higher anti-S IgG titres (p = 0.022). S-specific T-cell responses were seen after one vaccine in HCs and HSCT recipients. However, two vaccines enhanced S-specific T-cell responses in HCs but not in the majority of HSCT recipients. These data demonstrate limited immunogenicity of two-dose vaccination strategies in HSCT recipients, bolstering evidence of the need for additional boosters and/or alternative prophylactic measures in this group.

Keywords: BNT162b2; ChAdOx1; T-cell response; allogeneic bone marrow transplant; coronavirus disease 2019 (COVID-19); haematopoietic stem cell transplant (HSCT); severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2); vaccines.

FIGURE 1

Anti‐spike antibody response to coronavirus disease 2019 (COVID‐19) vaccines in HSCT recipients and HCs. Abbott anti‐spike immunoglobulin G titre (arbitrary units [au]/ml) at 28–56 days after the first dose of vaccine (V1) and 28–56 days after the second dose of vaccine (V2) in HSCT recipients (grey dots) and HCs (red dots). Individuals were vaccinated with either two doses of ChAdOx1 nCoV‐19 vaccine (left panel) or two doses of BNT162b2 vaccine (right panel). Bars and lines represent median and interquartile range. Statistical tests are Mann–Whitney U‐test for unpaired comparisons and Wilcox signed‐rank test between paired comparisons. HC, healthy control; HSCT, allogeneic haematopoietic stem cell transplant. p > 0.05, *p < 0.05, ***p < 0.001, ****p < 0.0001.

FIGURE 2

Cumulative anti‐SARS‐CoV‐2 S1 and S2 specific IFNγ T‐cell responses to coronavirus disease 2019 (COVID‐19) vaccines in HSCT recipients and HCs. Combined IFNγ T‐cell responses to peptide pools covering SARS‐CoV‐2 S1 and S2 by IFNγ enzyme‐linked immunospot assay in PBMCs of HSCT recipients (grey dots) and HCs (red dots) at 28–56 days after first vaccine (V1) and 28–56 days after second vaccine (V2). Individuals were vaccinated with either two doses of ChAdOx1 vaccine (left panel) or two doses of BNT162b2 vaccine (right panel). Data represent spot forming units (SFU)/10⁶ PBMC. Bars and lines represent median and interquartile range. Statistical tests are Mann–Whitney U‐test for unpaired comparisons and Wilcox signed‐rank test between paired comparisons. HC, healthy control; HSCT, allogeneic haematopoietic stem cell transplant; IFNγ, interferon‐gamma; PBMCs, peripheral blood mononuclear cells; SARS‐CoV‐2, severe acute respiratory syndrome coronavirus‐2. ns = p > 0.05, **p < 0.01.