Immunogenicity of SARS-CoV-2 mRNA Vaccine in Breast Cancer Patients Undergoing Active Treatment: A Prospective Observational Study

Understanding the immune response to SARS-CoV-2 vaccination in cancer patients remains a critical priority given their immunocompromised status. In this prospective observational study, we evaluated humoral and cellular immunity across three time points-baseline, post-second dose, and post-booster-in 23 breast cancer patients undergoing active treatment. IgG antibody levels showed a significant increase following vaccination, with a 300-fold rise after the second dose and a 2200-fold increase post-booster, indicating a strong humoral response. CD19⁺ B cells also increased significantly, supporting B cell-mediated activation. Although overall T cell frequencies remained stable, we observed a shift toward memory phenotypes, with decreased naïve CD4⁺ and CD8⁺ T cells and increased central and peripheral memory subsets after the booster. Notably, CD8⁺ TEMRA cells expanded significantly, suggesting cytotoxic memory formation. Correlation analyses linked peripheral memory CD4⁺ T cells with anti-SARS-CoV-2 IgG titers, while CD8⁺ TEMRA cells showed an inverse association. Antigen-specific CD8⁺ T cell response was evaluated using APC-labeled MHC I Dextramer reagents. After the booster, 55.5% of patients developed detectable antigen-specific CD8⁺ T cells, whereas 44.5% did not. Importantly, one patient who failed to develop antigen-specific CD8⁺ T cells experienced a mild SARS-CoV-2 infection, suggesting that the absence of this response may increase susceptibility despite high IgG levels. These findings indicate that antigen-specific CD8⁺ T cell responses and antibody levels may act as complementary but not directly correlated arms of immunity. Microbiota profiling via sPLS-DA suggested weak but distinct microbial signatures associated with immune responsiveness, particularly enrichment of taxa such as <i>Alistipes</i> and <i>Romoutsia</i> among high-antibody responders. These findings emphasize that SARS-CoV-2 vaccination is immunogenic and well tolerated in breast cancer patients under therapy and highlight the need to further explore microbiota-immune interactions to optimize vaccination strategies in oncology.