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. 2025 Jul 2:jiaf297.
doi: 10.1093/infdis/jiaf297. Online ahead of print.

Influenza-Specific T-Cell Responses to Vaccination Are Independent of Underlying Hematological Malignancy: Analysis of a Randomized Influenza Vaccination Trial

Victoria G Hall  1   2   3   4 , Thi H O Nguyen  4 , Olivia C Smibert  1   2   5 , Lilith F Allen  4 , Sheena G Sullivan  6   7   8 , Annette Fox  6 , Louise Carolan  6 , Adam K Wheatley  4 , Stephen J Kent  4 , Brad Gilbertson  4 , Chhay Lim  2 , Ian G Barr  6 , Heidi Peck  6 , Paula Fuge-Larsen  6 , Emily Klimevski  2 , Surekha Tennakoon  2 , Natalie R Saunders  2 , Trish Joyce  9 , Ashley Whitechurch  9 , Amit Khot  9 , Mary Ann Anderson  9 , Jason A Trubiano  5   7 , Leon J Worth  1   2 , Michelle K Yong  1   2   10 , Monica A Slavin  1   2   10 , Katherine Kedzierska  4 , Benjamin W Teh  1   2
Affiliations

Influenza-Specific T-Cell Responses to Vaccination Are Independent of Underlying Hematological Malignancy: Analysis of a Randomized Influenza Vaccination Trial

Victoria G Hall et al. J Infect Dis. .

Abstract

Background: There are few in-depth immunogenicity analyses of novel influenza vaccination strategies in high-risk patients with hematological malignancy (HM).

Methods: Participants receiving treatment for active HM (multiple myeloma [MM], chronic lymphocytic leukemia [CLL], or non-Hodgkin lymphoma [NHL]) in a randomized controlled trial of 2 doses of adjuvanted quadrivalent inactivated influenza vaccine (QIV) versus 2 doses of standard-dose QIV during 2022 were included. Hemagglutination (HA) inhibition assay and HA probe-specific B-cells were compared at baseline and 1, 2, and 6 months after the first vaccine dose (visits 1-4). A subset underwent ex vivo live virus infection of peripheral blood mononuclear cells at visits 1 and 3 with A/H1N1 and A/H3N2 to assess interferon (IFN) γ-producing CD4+ T cells, CD8+ T cells, natural killer cells, CD161+TRAV1-2+ mucosal-associated invariant T (MAIT)-like T cells and γδ T cells.

Results: In total, 62 patients with HM were analyzed (32 in the adjuvanted-dose and 30 in the standard-dose group), 13 (21.0%) with CLL, 24 (38.7%) MM, and 25 (40.3%) with NHL. Participants with MM had higher geometric mean antibody titers (P < .001) and influenza-specific B-cell responses for H1, H3, and B/Victoria at visits 2 and 3 than those with CLL or NHL (P < .05). The total CD19+ B-cell and HA probe-specific B-cell counts were found to significantly predict seroconversion at visits 2 and 3. Overall, with vaccination, there was an increase in the percentage frequency of B/Victoria influenza-specific B-cells (P = .01), IFN-γ-producing CD4+ T cells (P = .01) for A/H1N1 and IFN-γ-producing MAIT-like cells (P = .003) for A/H3N2.

Conclusions: Influenza strain-specific cellular responses were detectable following vaccination despite expected B-cell depletion in patients receiving active treatment for HM.

Clinical trials registration: Australian New Zealand Clinical Trials Registry ACTRN12622000454774.

Keywords: adaptive immunity; immunocompromise; influenza virus; innate immunity; vaccination.

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Conflict of interest statement

Potential conflicts of interest. V. G. H. is supported by the National Health and Medical Research Council (postgraduate PhD scholarship 2014210) and has received research funding from the Government of Victoria (VC2 biobank grant) and Moderna. S. G. S. reports consultancy or advisory roles for CSL Seqirus, Novavax, Moderna, Sanofi, and Evo Health. A. W. reports consultancy or advisory roles for AbbVie, AstraZeneca, and BeiGene and has received honoraria from Roche and Novartis. A. K. has received honoraria from Amgen, Janssen, Celgene/BMS, and Roche. M. A. A. has received honoraria from AbbVie, Janssen, Astrazeneca, Beigene, Novartis, Kite/Gilead, Roche, Takeda, and CSL. J. A. T. has received an investigator-initiated grant from MSD. M. K. Y. has received honoraria from MSD, Takeda, and Pfizer and research grant funding from MSD. M. A. S. has been on data safety monitoring and adjudication committees for Cidara, Roche, and Pfizer; has received research funding from Gilead Sciences, Merck, and F2G; has sat on advisory boards for Gilead Sciences, F2G, Cidara, Takeda, and Merck; and is supported by the Australian Government (National Health and Medical Research Council Investigator Grant 1173791 and Synergy Grant 2011100). B. W. T. has been on advisory boards for Moderna, Takeda, and CSL-Behring; has received research funding from MSD and Seqirus; has received honoraria, paid to their institution, from Pfizer, Alexion and Janssen; and is supported by the Australian Government (Medical Research Future Fund Investigator Fellowship EL-2, 1195894). All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.