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Immune responses to two and three doses of the BNT162b2 mRNA vaccine in adults with solid tumors
Rachna T Shroff1, Pavani Chalasani2, Ran Wei3
1Division of Hematology and Oncology, Department of Medicine, University of Arizona Cancer Center, Tucson, AZ, USA. rshroff@arizona.edu.
Abstract:
Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have shown high efficacy, but immunocompromised participants were excluded from controlled clinical trials. In this study, we compared immune responses to the BNT162b2 mRNA Coronavirus Disease 2019 vaccine in patients with solid tumors (n = 53) who were on active cytotoxic anti-cancer therapy to a control cohort of participants without cancer (n = 50). Neutralizing antibodies were detected in 67% of patients with cancer after the first immunization, followed by a threefold increase in median titers after the second dose. Similar patterns were observed for spike protein-specific serum antibodies and T cells, but the magnitude of each of these responses was diminished relative to the control cohort. In most patients with cancer, we detected spike receptor-binding domain and other S1-specific memory B cell subsets as potential predictors of anamnestic responses to additional immunizations. We therefore initiated a phase 1 trial for 20 cancer cohort participants of a third vaccine dose of BNT162b2 ( NCT04936997 ); primary outcomes were immune responses, with a secondary outcome of safety. At 1 week after a third immunization, 16 participants demonstrated a median threefold increase in neutralizing antibody responses, but no improvement was observed in T cell responses. Adverse events were mild. These results suggest that a third dose of BNT162b2 is safe, improves humoral immunity against SARS-CoV-2 and could be immunologically beneficial for patients with cancer on active chemotherapy.
Insights
Cancer patients on chemotherapy showed reduced immune responses to the first two doses of the SARS-CoV-2 (COVID-19) vaccine. A third dose improved antibody levels, suggesting a potential benefit for this immunocompromised group.
Area of Science:
- Immunology
- Oncology
- Vaccinology
Background:
- Controlled clinical trials for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines excluded immunocompromised individuals.
- Patients with cancer on active cytotoxic anti-cancer therapy represent a vulnerable, immunocompromised population.
- Understanding vaccine immunogenicity in this group is crucial for public health strategies.
Purpose of the Study:
- To compare immune responses to the BNT162b2 mRNA vaccine in patients with solid tumors undergoing chemotherapy versus a control group.
- To evaluate the safety and immunogenicity of a third BNT162b2 vaccine dose in cancer patients.
Main Methods:
- Comparative study of immune responses (neutralizing antibodies, serum antibodies, T cells) to BNT162b2 in 53 cancer patients and 50 controls.
- Phase 1 trial assessing immune responses and safety of a third BNT162b2 dose in 20 cancer patients.
- Measurement of spike protein-specific antibodies, neutralizing antibody titers, and T cell responses.
Main Results:
- Cancer patients exhibited diminished antibody and T cell responses after two vaccine doses compared to controls.
- Detection of spike receptor-binding domain and S1-specific memory B cells in most cancer patients.
- A third vaccine dose significantly increased neutralizing antibody titers in cancer patients, with mild adverse events.
- T cell responses did not improve after the third dose.
Conclusions:
- The BNT162b2 vaccine elicits a detectable, albeit diminished, immune response in cancer patients on chemotherapy.
- A third dose of BNT162b2 is safe and enhances humoral immunity against SARS-CoV-2 in this population.
- Further investigation into optimal vaccination strategies for immunocompromised cancer patients is warranted.
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