The SARS-CoV-2 pandemic still represents a threat for immunosuppressed and
hematological malignancy (HM) bearing patients, causing increased morbidity and mortality. Given the low anti-SARSCoV-2
IgG titers post-vaccination, the
COVID-19 threat prompted the prophylactic use of engineered anti-SARS-CoV-2
monoclonal antibodies. In addition, potential clinical significance of T cell responses has been overlooked during the first waves of the pandemic, calling for additional in-depth studies. We reported that the polarity and the repertoire of T cell immune responses govern the susceptibility to
SARS-CoV-2 infection in health care workers and solid
cancer patients. Here, we longitudinally analyzed humoral and cellular immune responses at each
BNT162b2 mRNA vaccine injection in 47 HM patients under
therapy. Only one-third of HM, mostly
multiple myeloma (MM) bearing patients, could mount S1-RBD-specific
IgG responses following
BNT162b2 mRNA vaccines. This
vaccine elicited a S1-RBD-specific Th1 immune response in about 20% patients, mostly in MM and
Hodgkin lymphoma, while exacerbating Th2 responses in the 10% cases that presented this recognition pattern at baseline (mostly
rituximab-treated patients). Performing a third booster barely improved the percentage of patients developing an S1-RBD-specific Th1 immunity and failed to seroconvert additional HM patients. Finally, 16 patients were infected with SARS-CoV-2, of whom 6 developed a severe
infection. Only S1-RBD-specific Th1 responses were associated with protection against SARS-CoV2
infection, while Th2 responses or anti-S1-RBD
IgG titers failed to correlate with protection. These findings herald the paramount relevance of
vaccine-induced Th1 immune responses in
hematological malignancies.