Immunogenicity of BNT162b2 vaccine Against the Alpha and Delta Variants in Immunocompromised Patients

Abstract

Background. The emergence of strains of SARS-CoV-2 exhibiting increase viral fitness and immune escape potential, such as the Delta variant (B.1.617.2), raises concerns in immunocompromised patients. To what extent Delta evades vaccine-induced immunity in immunocompromised individuals with systemic inflammatory diseases remains unclear. Methods. We conducted a prospective study in patients with systemic inflammatory diseases (cases) and controls receiving two doses of BNT162b2. Primary end points were anti-spike antibodies levels and cross-neutralization of Alpha and Delta variants after BNT162b2 vaccine. Secondary end points were T-cell responses, breakthrough infections and safety. Results. Sixty-four cases and 21 controls not previously infected with SARS-CoV-2 were analyzed. Kinetics of anti-spike IgG and IgA after BNT162b2 vaccine showed lower and delayed induction in cases, more pronounced with rituximab. Administration of two doses of BNT162b2 generated a neutralizing response against Alpha and Delta in 100% of controls, while sera from only one of rituximab-treated patients neutralized Alpha (5%) and none Delta. Other therapeutic regimens induced a partial neutralizing activity against Alpha, even lower against Delta. All controls and cases except those treated with methotrexate mounted a SARS-CoV-2 specific T-cell response. Methotrexate abrogated T-cell responses after one dose and dramatically impaired T-cell responses after 2 doses of BNT162b2. Conclusions. Rituximab and methotrexate differentially impact the immunogenicity of BNT162b2, by impairing B-cell and T-cell responses, respectively. Delta fully escapes the humoral response of individuals treated with rituximab. These findings support efforts to improve BNT162b2 immunogenicity in immunocompromised individuals (Funded by the Fonds IMMUNOV; ClinicalTrials.gov number, NCT04870411).

The T-cell clonal response to SARS-CoV-2 vaccination in inflammatory bowel disease patients is augmented by anti-TNF therapy and often deficient in antibody-responders

“…Although antibody response also peaks at 2 weeks 5 , antibody levels provided limited predictiveness for the T-cell clonal response induced by vaccination, particularly for individuals with a low T-cell response. This is consistent with findings reported from polyfunctional T-cell assessment 10 , 11 , 13 , 14 . In the context of reimmunization strategies, T-cell assessment may be important to evaluate both initial vaccine response and persistence of immunity after vaccination 15 , 16 .…”

“…Interrogation of our IBD patient cohort permitted assessment under select and discrete modes of therapeutic immunosuppression. Few studies have assessed the T-cell response to SARS-CoV-2 vaccines, and with few exceptions 12 have used methods that enumerate SARS-CoV-2-specific T-cells based on peptide-stimulated cytokine production 10 , 11 , 13 , 14 . Such studies don’t permit assessment of repertoire diversity and clonal size, important factors in protective T-cell immunity 3 , 4 .…”

Humoral and cellular immune responses on SARS-CoV-2 vaccines in patients with anti-CD20 therapies: a systematic review and meta-analysis of 1342 patients

“…Study characteristics of the included publications6–13 25–39 are summarised in table 1. Information to assay details of antibody detection and CMI are indicated in online supplemental appendix, pp.…”

“…We defined SARS-CoV-2 vaccine elicited humoral immune response as detection of antispike antibodies (anti-RBD or anti-S1 (spike protein) SARS-CoV-2) above the cut-off reported by the manufacturer of the given assay. Vaccine elicited cell-mediated immune response was defined as detection of SARS-CoV-2 specific T cells either measured by, T-EliSpot,6–9 interferon-γ release assays10 11 or activation-induced marker (AIM) detection12 13 in flow cytometry-sorted cells. AIM used for the detection of vaccine elicited T cells response were CD4 +CXCR5+PD1+and CD38+HLA-DR+12 as well as S-specific OX40 +41-BB+CD4+ and CD69+41BB+CD8+ 13…”

Immune Evasive Effects of SARS-CoV-2 Variants to COVID-19 Emergency Used Vaccines

“…However, whether gender is the factor to affect the immunization remains controversial (90,91). In immunocompromised individuals receiving immunosuppressive drugs, Hadjadj et al observed that antibody responses had partial neutralizing activity against Alpha, and even weaker against Delta stains, and their T cell responses were also altered (92). Therefore, immunosuppressive drugs for specific diseases might affect the vaccine-induced immunological effects.…”