Antibody response after second BNT162b2 dose in allogeneic HSCT recipients
Authors: Rabah Redjoul, Anne Le Bouter, Florence Beckerich, Slim Fourati, Sébastien Maury
Journal: The Lancet (2021)

The prognosis of COVID-19 infection is poor in hematopoietic stem-cell transplant (HSCT) recipients.1Sharma A Bhatt NS St Martin A et al.Clinical characteristics and outcomes of COVID-19 in haematopoietic stem-cell transplantation recipients: an observational cohort study.Lancet Haematol. 2021; 8: e185-e193Summary Full Text Full Text PDF PubMed Scopus (253) Google Scholar, 2Ljungman P de la Camara R Mikulska M et al.COVID-19 and stem cell transplantation; results from an EBMT and GETH multicenter prospective survey.Leukemia. 2021; (published online June 2.)https://doi.org/10.1038/s41375-021-01302-5Crossref PubMed Scopus (144) Google Scholar In a large multicentric series of 318 HSCT recipients (184 allogeneic HSCT recipients and 134 autologous HSCT recipients), the probability of overall survival at 30 days after the diagnosis of COVID-19 infection was notably dismal, at 68% (95% CI 58–77) and 67% (55–78) for allogeneic HSCT recipients and autologous HSCT recipients, respectively.1Sharma A Bhatt NS St Martin A et al.Clinical characteristics and outcomes of COVID-19 in haematopoietic stem-cell transplantation recipients: an observational cohort study.Lancet Haematol. 2021; 8: e185-e193Summary Full Text Full Text PDF PubMed Scopus (253) Google Scholar Immunocompromised patients have been excluded from initial studies of SARS-CoV-2 mRNA vaccine efficacy, so the efficacy of vaccination in this population warrants evaluation. To analyse the immunogenicity of the BNT162b2 mRNA vaccine (Pfizer–BioNTech), we used the IgG II Quant Assay (Abbot Laboratories, Wiesbaden, Germany) to quantify spike glycoprotein-specific IgG receptor-binding domain (IgG[S-RBD])levels at a median of 28 days (IQR 26–31) after the second vaccine dose in 88 recipients who had received two successive doses (at 4-week interval) at a median of 23 months (range 3–213 [IQR 9–30]) after allogeneic HSCT. IgG(S-RBD) titres could be quantified in 69 (78%) participants, whereas IgG(S-RBD) was detected but not quantifiable in three participants (anti-S titre <21 arbitrary unit [AU] per mL) and not detected in 16 participants (anti-S titre <6·8 AU/mL). In parallel, nucleoprotein-specific IgG was detected in seven of 88 participants, denoting previous SARS-CoV-2 exposure. As previously reported for surrogate measure of vaccine protection, we stratified samples by IgG(S-RBD) titres above or below 4160 AU/mL as this threshold has previously been shown to correspond to a 0·95 probability of virus neutralisation in in-vitro plaque reduction neutralisation tests.3Ebinger JE Fert-Bober J Printsev I et al.Antibody responses to the BNT162b2 mRNA vaccine in individuals previously infected with SARS-CoV-2.Nat Med. 2021; 27: 981-984Crossref PubMed Scopus (408) Google Scholar In a comparison of characteristics of patients with IgG(S-RBD) titres above (n=52) and below (n=36) this threshold, a time interval greater than 12 months between HSCT and vaccination, as well as an absolute lymphocyte count in peripheral blood above 1G/L at the time of vaccination correlated with protective IgG(S-RBD) titres after vaccination (appendix). In comparison, participants who had received systemic immunosuppressive drugs within 3 months of vaccination had subprotective IgG(S-RBD) titres. Systemic immunosuppressive treatments within 3 months of vaccination, together with a lymphocyte count below 1 G/L in peripheral blood, remained independently correlated with low IgG(S-RBD) titres in multivariable analysis, whereas the correlation with the time interval between HSCT and vaccination was lost. With a median follow-up of 84 days (range 44–121 [IQR 65–110]) after the first vaccination dose, we did not observe any COVID-19 infection in this cohort. In this first evaluation of immunogenicity in allogeneic HSCT recipients after two vaccine doses, we observed overall frequent and high levels of humoral responses, which contrasts with recent observations in solid organ transplant recipients who are receiving very long-term pharmacological immunosuppression.4Boyarsky BJ Werbel WA Avery RK et al.Antibody response to 2-dose SARS-CoV-2 mRNA vaccine series in solid organ transplant recipients.JAMA. 2021; 325: 2204-2206Crossref PubMed Scopus (751) Google Scholar We identified lymphocyte count as well as recent pharmacological immunosuppression, rather than the sole timing of vaccination after HSCT, as determinants of humoral response. Our findings support the large scale vaccination of allogeneic HSCT recipients, although additional multicentre and long-term studies are needed to specify the level of immunological protection against infection, also taking into account the effect of a third vaccine dose in non-responding patients. We declare no competing interests. Download .pdf (.14 MB) Help with pdf files Supplementary appendix Clinical characteristics and outcomes of COVID-19 in haematopoietic stem-cell transplantation recipients: an observational cohort studyRecipients of autologous and allogeneic HSCT who develop COVID-19 have poor overall survival. These data emphasise the need for stringent surveillance and aggressive treatment measures in HSCT recipients who develop COVID-19. Full-Text PDF