ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 2186

Cellular and Humoral Responses Following SARS-CoV-2 mRNA Vaccination in Patients on PD-1 Immunotherapy with irAEs

Sokratis Apostolidis1, Paulina Coutifaris2, Mark Painter3, Ajinkya Pattekar2, Rishi Goel1, divij mathew2, Wenzhao Meng2, Kevin Wang2, Bria Fulmer2, Angela Corrigan2, Kendall Lundgreen2, Elizabeth Drapeau2, Derek Oldridge2, Josephine Giles2, Amy Baxter2, Sasikanth Manne2, Michelle Mckeague2, Ahron Flowers2, Oliva Kuthuru2, Sherea Long2, Jeanette Dougherty2, Sigrid Gouma2, Justine Williams2, Maura McLaughlin2, Sharon Adamski2, Alba Grifoni4, Daniela Weiskopf4, Alessandro Sette4, Scott Hensley2, Paul Bates2, Eline Luning Prak1, Laura Vella2, Giorgos Karakousis2, Ravi Amaravadi2, Suzanne McGettigan2, Kristin Kreider2, Tara Mitchell2, Allison Greenplate2, Lynn Schuchter2, Alexander Huang2 and E. John Wherry1, 1University of Pennsylvania, Philadelphia, PA, 2UPenn, Philadelphia, 3UPenn, Philadelphia, PA, 4LJI, La Jolla

Meeting: ACR Convergence 2022

Keywords: , ,

Session Information

Date: Monday, November 14, 2022

Session Title: Abstracts: T Cell Biology and Targets in Autoimmune and Inflammatory Disease

Session Type: Abstract Session

Session Time: 3:00PM-4:00PM

Background/Purpose: Patients with cancer exhibit increased mortality from SARS-CoV-2 infection compared to the general population. SARS-CoV-2 mRNA vaccination in healthy individuals generates effective and long-lasting immune protection against COVID-19. PD-1 is highly expressed on the surface of T follicular helper cells that play a central role in T cell dependent B cell vaccine responses. Here, we sought to investigate the cellular and humoral responses in patients on PD-1 immunotherapy after SARS-CoV-2 mRNA vaccination, with a particular focus on patients developing immune-related adverse events (irAEs).

Methods: We investigated the longitudinal induction of antigen-specific antibody, B cell and T cell responses in patients with melanoma on anti-PD-1 immunotherapy (aPD-1, n = 44) receiving a 2-dose SARS-CoV-2 mRNA vaccine regimen during 6 distinct timepoints over the course of 9 months (Figure 1). We compared these responses against an established cohort of healthy control individuals (HC, n=45). All individuals included in this study were not previously infected with SARS-CoV-2. Incidence of irAEs in the aPD-1 patients was determined with retrospective chart review.

Results: After a 2-dose mRNA vaccine regimen, a-PD1 patients had lower levels of anti-Spike IgG after the first vaccine dose (V2) and lower levels of anti-Receptor Binding Domain (RBD) IgG after the first and second dose (V2 and V4) compared to healthy controls (Figure 2). Within the aPD-1 patient group, patients with irAEs demonstrated a trend towards lower anti-Spike and anti-RBD IgG compared to patients with no irAEs (Figure 3). Vaccine-specific memory B cells (mBCs) recognizing Spike and RBD were generated in patients on aPD-1 therapies to an extent equivalent to healthy controls. The mBCs from aPD-1 patients efficiently recognized the Alpha, Beta and Delta variants of concern (VOC) of SARS-CoV-2 but exhibited diminished recognition of the Omicron variant at 2 months after the 2nd vaccination (V5). This defect improved over time, with mBCs from aPD-1 patients recognizing the Omicron VOC at levels similar to the control group by 6-9 months following primary vaccination (V6). Finally, using a peptide pool of the wild-type Spike protein, we found that all aPD-1 patients generated antigen-specific CD4 and CD8 T-cell responses following vaccination. Nevertheless, when tested with an omicron-specific peptide pool, the abundance of antigen-specific CD4 T cells, but not CD8 T cells, from patients on aPD-1 immunotherapy was lower than that of healthy controls.

Conclusion: These results indicated that patients on aPD-1 immunotherapeutics generate productive humoral and cellular vaccine-specific responses against the wild-type Spike protein following SARS-CoV-2 mRNA vaccination. However, they also demonstrated diminished B cell and CD4 T cell recognition of the immune-evasive Omicron variant. In addition, patients with irAEs showed some of the lower serological responses among all the individuals tested. The qualitative defects seen in patients on aPD-1 therapy highlight the importance of the PD-1 pathway in promoting fully functional vaccine responses, suggesting possibly a more pressing need for these patients to receive booster vaccinations.

Supporting image 1

Figure 1. Schematic representation of the study design and blood draw schedule.

Supporting image 2

Figure 2. Anti-Spike (left) and anti-RBD (right) IgG in the healthy and the aPD_1 melanoma groups. The two groups were compared with non-parametric testing (Wilcoxon test) at each timepoint with Benjamini-Hochberg correction applied for multiple comparisons. * <0.05 and ** <0.01.

Supporting image 3

Figure 3. Anti-RBD IgG shown for aPD_1 patients without (red) and with (blue) history of irAEs.

Disclosures: S. Apostolidis, None; P. Coutifaris, None; M. Painter, None; A. Pattekar, None; R. Goel, None; d. mathew, None; W. Meng, None; K. Wang, None; B. Fulmer, None; A. Corrigan, None; K. Lundgreen, None; E. Drapeau, None; D. Oldridge, None; J. Giles, None; A. Baxter, None; S. Manne, None; M. Mckeague, None; A. Flowers, None; O. Kuthuru, None; S. Long, None; J. Dougherty, None; S. Gouma, None; J. Williams, None; M. McLaughlin, None; S. Adamski, None; A. Grifoni, None; D. Weiskopf, None; A. Sette, None; S. Hensley, None; P. Bates, None; E. Luning Prak, None; L. Vella, None; G. Karakousis, None; R. Amaravadi, None; S. McGettigan, None; K. Kreider, None; T. Mitchell, None; A. Greenplate, None; L. Schuchter, None; A. Huang, None; E. Wherry, Merck/MSD, Janssen, Surface Oncology, Synthekine.

To cite this abstract in AMA style:

Apostolidis S, Coutifaris P, Painter M, Pattekar A, Goel R, mathew d, Meng W, Wang K, Fulmer B, Corrigan A, Lundgreen K, Drapeau E, Oldridge D, Giles J, Baxter A, Manne S, Mckeague M, Flowers A, Kuthuru O, Long S, Dougherty J, Gouma S, Williams J, McLaughlin M, Adamski S, Grifoni A, Weiskopf D, Sette A, Hensley S, Bates P, Luning Prak E, Vella L, Karakousis G, Amaravadi R, McGettigan S, Kreider K, Mitchell T, Greenplate A, Schuchter L, Huang A, Wherry E. Cellular and Humoral Responses Following SARS-CoV-2 mRNA Vaccination in Patients on PD-1 Immunotherapy with irAEs [abstract]. Arthritis Rheumatol. 2022; 74 (suppl 9). https://acrabstracts.org/abstract/cellular-and-humoral-responses-following-sars-cov-2-mrna-vaccination-in-patients-on-pd-1-immunotherapy-with-iraes/. Accessed February 3, 2023.

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