Impaired SARS-CoV-2 Variant Neutralization and CD8+ T-cell Responses Following 3 Doses of mRNA Vaccines in Myeloma: Correlation with Breakthrough Infections

Autor: Maryam I. Azeem, Ajay K. Nooka, Uma Shanmugasundaram, Narayanaiah Cheedarla, Sayalee Potdar, Renee Julia Manalo, Alberto Moreno, Jeffrey M. Switchenko, Suneethamma Cheedarla, Deon Bryant Doxie, Roman Radzievski, Madison Leigh Ellis, Kelly E. Manning, Bushra Wali, Rajesh M. Valanparambil, Kathryn T. Maples, Essence Baymon, Jonathan L. Kaufman, Craig C. Hofmeister, Nisha S. Joseph, Sagar Lonial, John D. Roback, Alessandro Sette, Rafi Ahmed, Mehul S. Suthar, Andrew S. Neish, Madhav V. Dhodapkar, Kavita M. Dhodapkar
Rok vydání: 2022
Předmět:
Zdroj: Blood Cancer Discovery. 4:106-117
ISSN: 2643-3249
2643-3230
Popis: Patients with multiple myeloma (MM) mount suboptimal neutralizing antibodies (nAb) following 2 doses of SARS-CoV-2 mRNA vaccines. Currently, circulating SARS-CoV-2 variants of concern (VOC) carry the risk of breakthrough infections. We evaluated immune recognition of current VOC including BA.1, BA.2, and BA.5 in 331 racially representative patients with MM following 2 or 3 doses of mRNA vaccines. The third dose increased nAbs against WA1 in 82%, but against BA variants in only 33% to 44% of patients. Vaccine-induced nAbs correlated with receptor-binding domain (RBD)–specific class-switched memory B cells. Vaccine-induced spike-specific T cells were detected in patients without seroconversion and cross-recognized variant-specific peptides but were predominantly CD4+ T cells. Detailed clinical/immunophenotypic analysis identified features correlating with nAb/B/T-cell responses. Patients who developed breakthrough infections following 3 vaccine doses had lower live-virus nAbs, including against VOC. Patients with MM remain susceptible to SARS-CoV-2 variants following 3 vaccine doses and should be prioritized for emerging approaches to elicit variant-nAb and CD8+ T cells.Significance:Three doses of SARS-CoV-2 mRNA vaccines fail to yield detectable VOC nAbs in nearly 60% and spike-specific CD8+ T cells in >80% of myeloma patients. Patients who develop breakthrough infections following vaccination have low levels of live-virus nAb.This article is highlighted in the In This Issue feature, p. 101
Databáze: OpenAIRE
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