tetano
Editor, Senior Moderator
Nat Med
. 2021 Sep 30.
doi: 10.1038/s41591-021-01542-z. Online ahead of print.
Immune responses to two and three doses of the BNT162b2 mRNA vaccine in adults with solid tumors
Rachna T Shroff[SUP] 1 [/SUP], Pavani Chalasani[SUP] 2 [/SUP], Ran Wei[SUP] 3 [/SUP], Daniel Pennington[SUP] 2 [/SUP], Grace Quirk[SUP] 4 [/SUP], Marta V Schoenle[SUP] 3 4 [/SUP], Kameron L Peyton[SUP] 3 [/SUP], Jennifer L Uhrlaub[SUP] 3 [/SUP], Tyler J Ripperger[SUP] 3 [/SUP], Mladen Jergović[SUP] 3 [/SUP], Shelby Dalgai[SUP] 2 [/SUP], Alexander Wolf[SUP] 2 [/SUP], Rebecca Whitmer[SUP] 5 [/SUP], Hytham Hammad[SUP] 2 [/SUP], Amy Carrier[SUP] 2 [/SUP], Aaron J Scott[SUP] 2 [/SUP], Janko Nikolich-Žugich[SUP] 3 4 6 [/SUP], Michael Worobey[SUP] 4 7 [/SUP], Ryan Sprissler[SUP] 4 8 [/SUP], Michael Dake[SUP] 9 [/SUP], Bonnie J LaFleur[SUP] 10 [/SUP], Deepta Bhattacharya[SUP] 11 12 [/SUP]
Affiliations
Abstract
Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have shown high efficacy, but immunocompromised participants were excluded from controlled clinical trials. In this study, we compared immune responses to the BNT162b2 mRNA Coronavirus Disease 2019 vaccine in patients with solid tumors (n = 53) who were on active cytotoxic anti-cancer therapy to a control cohort of participants without cancer (n = 50). Neutralizing antibodies were detected in 67% of patients with cancer after the first immunization, followed by a threefold increase in median titers after the second dose. Similar patterns were observed for spike protein-specific serum antibodies and T cells, but the magnitude of each of these responses was diminished relative to the control cohort. In most patients with cancer, we detected spike receptor-binding domain and other S1-specific memory B cell subsets as potential predictors of anamnestic responses to additional immunizations. We therefore initiated a phase 1 trial for 20 cancer cohort participants of a third vaccine dose of BNT162b2 ( NCT04936997 ); primary outcomes were immune responses, with a secondary outcome of safety. At 1 week after a third immunization, 16 participants demonstrated a median threefold increase in neutralizing antibody responses, but no improvement was observed in T cell responses. Adverse events were mild. These results suggest that a third dose of BNT162b2 is safe, improves humoral immunity against SARS-CoV-2 and could be immunologically beneficial for patients with cancer on active chemotherapy.
. 2021 Sep 30.
doi: 10.1038/s41591-021-01542-z. Online ahead of print.
Immune responses to two and three doses of the BNT162b2 mRNA vaccine in adults with solid tumors
Rachna T Shroff[SUP] 1 [/SUP], Pavani Chalasani[SUP] 2 [/SUP], Ran Wei[SUP] 3 [/SUP], Daniel Pennington[SUP] 2 [/SUP], Grace Quirk[SUP] 4 [/SUP], Marta V Schoenle[SUP] 3 4 [/SUP], Kameron L Peyton[SUP] 3 [/SUP], Jennifer L Uhrlaub[SUP] 3 [/SUP], Tyler J Ripperger[SUP] 3 [/SUP], Mladen Jergović[SUP] 3 [/SUP], Shelby Dalgai[SUP] 2 [/SUP], Alexander Wolf[SUP] 2 [/SUP], Rebecca Whitmer[SUP] 5 [/SUP], Hytham Hammad[SUP] 2 [/SUP], Amy Carrier[SUP] 2 [/SUP], Aaron J Scott[SUP] 2 [/SUP], Janko Nikolich-Žugich[SUP] 3 4 6 [/SUP], Michael Worobey[SUP] 4 7 [/SUP], Ryan Sprissler[SUP] 4 8 [/SUP], Michael Dake[SUP] 9 [/SUP], Bonnie J LaFleur[SUP] 10 [/SUP], Deepta Bhattacharya[SUP] 11 12 [/SUP]
Affiliations
- PMID: 34594036
- DOI: 10.1038/s41591-021-01542-z
Abstract
Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have shown high efficacy, but immunocompromised participants were excluded from controlled clinical trials. In this study, we compared immune responses to the BNT162b2 mRNA Coronavirus Disease 2019 vaccine in patients with solid tumors (n = 53) who were on active cytotoxic anti-cancer therapy to a control cohort of participants without cancer (n = 50). Neutralizing antibodies were detected in 67% of patients with cancer after the first immunization, followed by a threefold increase in median titers after the second dose. Similar patterns were observed for spike protein-specific serum antibodies and T cells, but the magnitude of each of these responses was diminished relative to the control cohort. In most patients with cancer, we detected spike receptor-binding domain and other S1-specific memory B cell subsets as potential predictors of anamnestic responses to additional immunizations. We therefore initiated a phase 1 trial for 20 cancer cohort participants of a third vaccine dose of BNT162b2 ( NCT04936997 ); primary outcomes were immune responses, with a secondary outcome of safety. At 1 week after a third immunization, 16 participants demonstrated a median threefold increase in neutralizing antibody responses, but no improvement was observed in T cell responses. Adverse events were mild. These results suggest that a third dose of BNT162b2 is safe, improves humoral immunity against SARS-CoV-2 and could be immunologically beneficial for patients with cancer on active chemotherapy.