Lack of Induction of RBD-Specific Neutralizing Antibodies despite Repeated Heterologous SARS-CoV-2 Vaccination Leading to Seroconversion and Establishment of T Cell-Specific Memory in a Patient in Remission of Multiple Myeloma.

Bernhard Kratzer,Al Nasar Ahmed Sehgal,Teresa Oberhofer,Gerhard H Kopetzky,Katharina Grabmeier-Pfistershammer,Doris Trapin,Franz Tischer,Petra Waidhofer-Söllner,Arno Rottal,Ulrike Körmöczi,Rudolf Valenta,Pia Gattinger,Winfried F Pickl

doi:10.3390/vaccines10030374

Abstract

Background: Prophylactic vaccination against infectious diseases may induce a state of long-term protection in the otherwise healthy host. However, the situation is less predictable in immunocompromised patients and may require adjustment of vaccination schedules and/or basic therapy. Methods: A patient in full remission of multiple myeloma since the last three years and on long-term maintenance therapy with pomalidomide, a drug inhibiting angiogenesis and myeloma cell growth, was vaccinated twice with Comirnaty followed by two vaccinations with Vaxzevria. Seroconversion and SARS-CoV-2-specific cellular responses were monitored. Results: No signs of seroconversion or T cellular memory were observed after the first “full immunization” with Comirnaty. Consequently, long-term-maintenance therapy with Pomalidomide was stopped and two additional shots of Vaxzevria were administered after which the patient seroconverted with Spike(S)-protein specific antibody levels reaching 49 BAU/mL, mild S-peptide pool-specific T cell proliferation, effector cytokine production (IL-2, IL-13), and T cellular activation with increased numbers of CD3+CD4+CD25+ T cells as compared to vaccinated and non-vaccinated control subjects. However, despite suspension of immunosuppression and administration of in total four consecutive heterologous SARS-CoV-2 vaccine shots, the patient did not develop neutralizing RBD-specific antibodies. Conclusions: Despite immunomonitoring-based adjustment of vaccination and/or therapy schedules vaccination success, with clear correlates of protection, the development of RBD-specific antibodies could not be achieved in the immunocompromised patient with current SARS-CoV-2 vaccines. Thus, our report emphasizes the need for improved active and passive immunization strategies for SARS-CoV-2 infections.

Highlights

In healthy individuals, SARS-CoV-2 genetic vaccines are generally very successful, inducing high levels of spike protein (S)-specific antibodies in parallel with SARS-CoV-2specific T-cell memory [1–5]
Repeated Heterologous Immunization with mRNA- Followed by Vector-Based SARS-CoV-2 Vaccines Leads to Seroconversion, without Induction of Neutralizing anti-receptor binding domain (RBD) Antibodies
We here investigated in detail the vaccination response in a patient who suffered from multiple myeloma more than four years ago, achieved full remission more than three

Summary

Introduction

SARS-CoV-2 genetic vaccines are generally very successful, inducing high levels of spike protein (S)-specific antibodies in parallel with SARS-CoV-2specific T-cell memory [1–5]. The patient described in this study is a non-responder to full vaccination with two doses and we report on the outcome of an additional full course of two doses with a heterologous vaccine. Obtained results from this patient highlight the need for improved active or passive immunization strategies for poor responders treated with available COVID-19 vaccines. Long-term-maintenance therapy with Pomalidomide was stopped and two additional shots of Vaxzevria were administered after which the patient seroconverted with Spike(S)-protein specific antibody levels reaching 49 BAU/mL, mild S-peptide pool-specific T cell proliferation, effector cytokine production (IL-2, IL-13), and T cellular activation with increased numbers of CD3+CD4+CD25+ T cells as compared to vaccinated and non-vaccinated control subjects. Our report emphasizes the need for improved active and passive immunization strategies for SARS-CoV-2 infections

Methods

Results

Conclusion