Immunogenicity Research of SARS-CoV-2 mRNA Vaccine

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes significant morbidity and mortality, particularly among vulnerable immunosuppressed cancer patients. From observational studies, messenger RNA (mRNA) SARS-CoV-2 vaccines, BNT162b2, and mRNA-1273 show reduced antibody response in cancer patients compared to healthy individuals. Patients with selected hematological malignancies and those receiving specific anticancer treatments may have low or no antibody response following vaccination. While it is believed that vaccine-induced responses are robust up to six months, and clinically significant breakthrough infections appear to be rare in healthy individuals, the kinetics of immune response and incidence of breakthrough infections are unclear in patients receiving concurrent therapy for malignancy. There is an urgent need to understand long-term immunogenicity of SARS-CoV-2 vaccines among cancer patients to inform evidence-based guidance for subsequent timing and frequency of booster vaccinations.

To optimize clinical experiments, longitudinal studies of SARS-CoV-2 vaccine-induced immune responses in cancer patients are needed. In a prospective cohort study of 366 (291 vaccinated) patients, antibody levels [anti-spike (IgG-(S-RBD)) and anti-nucleocapsid immunoglobulin were measured at three timepoints. (1.enrollment (prior to dose 1 vaccination for vaccinated patients, n=112); 2.peak response (2–12 weeks post two-dose for vaccinated patients, n=147) and 3.sustained response (16–28 weeks post two-dose for vaccinated patients, n=124). IgG-(S-RBD) at peak response was higher and remained higher after 4-6 months in patients receiving mRNA-1273 compared to BNT162b2. Patients with solid tumors attained higher peak levels and sustained levels after 4-6 months (p<0.001) compared to those with hematologic malignancies. Solid tumor patients receiving immune checkpoint inhibitors before vaccination had lower sustained antibody levels than those who received treatment after vaccination (p=0.043). Two (0.69%) vaccinated and one (1.9%) unvaccinated patient had severe COVID-19 illness during follow-up. Differences in antibody responses were partly explained by differences in treatment regimens, timing between vaccination and treatment, mRNA vaccine type, age, and ethnicity. All cases of severe illness/death occurred in hematologic malignancy patients; additional approaches may be needed to protect these individuals from COVID-19. This study shows variation in sustained antibody responses across cancer populations receiving various therapeutic modalities with important implications for vaccine booster timing and patient selection.

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References DOI : 10.1158/0008-5472.CAN-21-3554