# Follow-up of humoral and cellular immune responses after the third SARS-CoV-2 vaccine dose in multiple myeloma patients

**Authors:** Vincenzo Raimondi, Paola Storti, Rosanna Vescovini, Valentina Franceschi, Denise Toscani, Laura Notarfranchi, Anna Benedetta Dalla Palma, Nicolas Thomas Iannozzi, Sergio Minesso, Matteo Scita, Oxana Lungu, Mattia Dessena, Gaetano Donofrio, Nicola Giuliani

PMC · DOI: 10.3389/fimmu.2025.1532947 · 2025-02-18

## TL;DR

This study tracks immune responses in multiple myeloma patients after a third SARS-CoV-2 vaccine dose, finding that immunity declines over time but can be boosted by additional vaccines or infections.

## Contribution

The study provides new insights into the durability of humoral and cellular immunity in multiple myeloma patients after third SARS-CoV-2 vaccination.

## Key findings

- Neutralizing antibodies and CD8+ T cell responses declined significantly after 26 weeks post-third dose.
- Additional vaccination or breakthrough infection boosted antibody levels and stabilized T cell responses.
- Patients with only three doses had higher breakthrough infection rates during 32 weeks of follow-up.

## Abstract

The stability of immune responses to SARS-CoV-2 vaccines, especially concerning the cross-reactive recognition of the Omicron variant, remains incompletely characterized in multiple myeloma (MM) patients. This study evaluated humoral responses in 29 MM patients and cellular responses in a subset of 19 MM patients, specific to Wuhan and Omicron spike proteins, between 16 and 26 weeks following the third vaccine dose. After 26 weeks, we highlighted a significant reduction in the neutralizing antibodies to both spikes and the percentages of IFN-γ+CD107a+ spike-specific CD8+ T cells. On the other hand, patients who underwent an additional stimulation between the two time points, through either a fourth vaccine dose or breakthrough infection, showed a significant increase in neutralizing antibodies and stable levels of cytotoxic CD8+ T cells. Additionally, those with only three doses experienced a higher rate of breakthrough infections during the 32-week follow-up period. These findings underscore the waning of vaccine-induced immunity over time and may help benefit-risk evaluation in vaccination strategies in MM patients.

## Linked entities

- **Proteins:** CHMP5 (charged multivesicular body protein 5), IFNG (interferon gamma), LAMP1 (lysosome associated membrane protein 1), CD8A (CD8 subunit alpha)
- **Diseases:** multiple myeloma (MONDO:0009693), SARS-CoV-2 (MONDO:0100096)

## Full-text entities

- **Genes:** IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, LAMP1 (lysosome associated membrane protein 1) [NCBI Gene 3916] {aka CD107a, LAMPA, LGP120}
- **Diseases:** infection (MESH:D007239), MM (MESH:D009101)
- **Species:** Severe acute respiratory syndrome coronavirus 2 (no rank) [taxon 2697049], Homo sapiens (human, species) [taxon 9606]

## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC11876378/full.md

---
Source: https://tomesphere.com/paper/PMC11876378