Longitudinal data on humoral response and neutralizing antibodies against SARS-CoV-2 Omicron BA.1 and subvariants BA.4/5 and BQ.1.1 after COVID-19 vaccination in cancer patients

Abstract

Purpose The SARS-CoV-2 Omicron variant of concern (VOC) and subvariants like BQ.1.1 demonstrate immune evasive potential. Little is known about the efficacy of booster vaccinations regarding this VOC and subvariants in cancer patients. This study is among the first to provide data on neutralizing antibodies (nAb) against BQ.1.1. Methods Cancer patients at our center were prospectively enrolled between 01/2021 and 02/2022. Medical data and blood samples were collected at enrollment and before and after every SARS-CoV-2 vaccination, at 3 and 6 months. Results We analyzed 408 samples from 148 patients (41% female), mainly with solid tumors (85%) on active therapy (92%; 80% chemotherapy). SARS-CoV-2 IgG and nAb titers decreased over time, however, significantly increased following third vaccination (p < 0.0001). NAb (ND50) against Omicron BA.1 was minimal prior and increased significantly after the third vaccination (p < 0.0001). ND50 titers against BQ.1.1 after the third vaccination were significantly lower than against BA.1 and BA.4/5 (p < 0.0001) and undetectable in half of the patients (48%). Factors associated with impaired immune response were hematologic malignancies, B cell depleting therapy and higher age. Choice of vaccine, sex and treatment with chemo-/immunotherapy did not influence antibody response. Patients with breakthrough infections had significantly lower nAb titers after both 6 months (p < 0.001) and the third vaccination (p = 0.018). Conclusion We present the first data on nAb against BQ.1.1 following the third vaccination in cancer patients. Our results highlight the threat that new emerging SARS-CoV-2 variants pose to cancer patients and support efforts to apply repeated vaccines. Since a considerable number of patients did not display an adequate immune response, continuing to exhibit caution remains reasonable.

COVID-19–Sensitive Tumour Response – 2-Year Assessment of the SARS-CoV-2 Humoral Response in Cancer Patients in Oncology Hospital in Poland

“…In the summary of the work, administering at least three doses of mRNA vaccine should serve as the basis for immunization, and a three-month interval may be the best alternative to the vaccination schedule for nonimmunocompromised (healthy) people. Our observations were confirmed in the works of other authors [6].…”

“…In the literature, we find data that only every third patient with diagnosed cancer undergoing anticancer therapy responds to the complete 2-dose vaccination by producing antibodies [5]. The booster effect (third dose) equalizes the chances between patients' subpopulations during oncological treatment [6,7].…”

Neutralizing Antibody Response following a Third Dose of the mRNA-1273 Vaccine among Cancer Patients

“…Patients with solid tumor malignancies had much stronger immune responses than those with HMs (likely due to B-cell defects [22,23]) 4 weeks after the third dose; however, this statistical difference was lost at 6 months, results that are similar to those published for other mRNA vaccines [24]. Neutralizing antibody responses at 28 days post-dose 3 were reduced in patients who had lower lymphocyte counts (≤1 × 10 9 /L) and those who had received anticancer therapies in the last 3 months, particularly those that received BTK inhibitors, small molecules, anti-CD20 antibodies, and anti-CD38 antibodies (results also noted in other studies) [25][26][27][28]. Most importantly, we observed increased neutralization GMTs, regardless of cancer type or treatment, even in patients that were seronegative prior to dose 3 (similar to the total antibody GMT increase previously described [18]), and at 6 months following the receipt of the third vaccine dose, those titers were still at least 10-fold greater than those recorded prior to dose 3.…”

“…Our study had a few limitations, the first being that we did not determine immunogenicity against different SARS-CoV-2 variants, particularly the Omicron variant, against which existing data show reduced vaccine efficacy [ 25 , 31 , 32 ]. The number of patients in each subcategory for analysis was lower in some therapies than others, limiting our ability to make conclusions for certain patient subsets.…”