After 3 doses of COVID vaccine, most cancer patients retain detectable humoral immunity

In a recent study posted to the medRxiv* preprint server, researchers assessed the efficacy and durability of immune responses to the third dose of coronavirus disease 2019 (COVID-19) vaccines. They also assessed the efficacy of the fourth vaccine dose among severely immunocompromised patients with hematological malignancies.

Cancer patients show increased morbidity with COVID-19 and need effective immunization strategies. As a result of COVID-19 vaccinations and better antimicrobials against SARS-CoV-2 variants, case fatality rates have dropped with time. However, case fatality rates were high among cancer patients against the SARS-CoV-2 Omicron variant. Greater age and comorbidities have been reported to be prime factors that adversely affect outcomes among cancer patients.

Previously, the authors of the present study observed a profound beneficial impact of the third (booster) vaccination with >50% seroconversion of individuals who were seronegative following primary vaccination. They also reported 56% seroconversion among cancer patients who were seronegative after double COVID-19 vaccinations.

Study: Efficacy and longevity of immune response to 3rd COVID-19 vaccine and effectiveness of a 4th dose in severely immunocompromised patients with cancer. Image Credit: Steve Heap / Shutterstock

About the study

In the present study, the researchers from Montefiore Einstein Cancer Center,  Albert Einstein College of Medicine,  Icahn School of Medicine at Mount Sinai, and  Euroimmun US completed their previous analysis by evaluating the effectiveness and durability of immune responses to the third dose of COVID-19 vaccines and expanded assessments among severely immunocompromised patients with hematological malignancies by evaluating the fourth vaccine dose efficacy.

For the third dose study, participants aged >18 were diagnosed with cancer and either received active therapy or required active surveillance. Before enrolment, all patients had received double COVID-19 mRNA vaccines or single adenoviral vaccination and were administered boosters of BNT162b2 or mRNA-1273 vaccines in the present analysis.

Follow-up assessments were performed after four weeks and after four to six months of booster vaccinations. Patients who received Ad26.CoV2.S vaccinations were initially administered with BNT162b2 vaccine boosters in the present study. For the fourth dose study, hematological patients who elicited no or low [<1000 arbitrary units (AU)/ml] immune responses two weeks after the third mRNA vaccine dose were administered the fourth dose of BNT162b2 (mRNA vaccine) or adenoviral vaccines.

The durability of immune responses was based on the antibody titers against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein subunit 1 (S1) receptor-binding domain (RBD), T lymphocyte activity and neutralization of SARS-CoV-2 wild-type (WT) strain and Omicron BA.1 strain. Seroconversion was assessed based on the cluster of differentiation 19 (CD19) counts and immunoglobulin M (IgM) titers. In addition, complete blood counts (CBC), IgA, and IgG titers were also assessed.

The antibody titers were measured using chemiluminescent assays and their median values were noted. T lymphocyte responses were assessed using interferon-gamma release assays (IGRA). In addition, surrogate virus neutralization tests (sVNT) were performed to measure titers of antibodies that prevent S RBD-hACE2(human angiotensin-converting enzyme 2) interactions and microneutralization (MNT) assays were performed. Further, the associations between particular anti-cancer treatments and booster vaccinations were determined.

Results

The third vaccine dose led to seroconversion among 57% of patients (20 out of 35) who were seronegative following the prime vaccination and the immune responses generated were durable. The baseline anti-S titer was 212 AU/mL, which substantially increased after four weeks of third dose administration to 9997 AU/mL.

Likewise, the fourth dose boosted immune responses with 67% seroconversion (12 out of 18 patients) of severely immunosuppressed hematological malignancy patients who were seronegative post-third vaccine dose; however, responses against Omicron were low. The increase in anti-S titers among hematological malignancy patients was 2167 AU/mL, respectively. In the hematological malignancy group, lymphoid cancer patients demonstrated a lesser elevation in anti-S titers (1169 AU/mL) than myeloid cancer patients (9424 AU/mL).

Patients receiving Bruton tyrosine kinase inhibitor (BTKi) therapy and anti-CD20 monoclonal antibody therapy did not demonstrate any improvements in the anti-S titers post booster vaccination. Nine participants with previous SARS-CoV-2 exposure demonstrated a greater rise in anti-S titers (19350 AU/mL) than those without prior COVID-19 history (6706 AU/mL).

Further, the elevations in anti-S titers were greater among individuals who received mRNA-1273 boosters (31451 AU/mL) than those who received BNT162b2 boosters (5534 AU/mL) at the fourth-week follow-up, although the finding did not attain statistical significance. T lymphocyte responses and neutralizing antibody titers correlated with the anti-S titer findings at the fourth-week follow-up and the anti-S titers were maintained even after six months of booster vaccinations.

Overall, the study findings showed that booster doses of COVID-19 vaccines induced durable immune responses among patients with hematological malignancies and indicated that additional vaccine doses could potentiate immune responses.

*Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Written by

Pooja Toshniwal Paharia

Dr. based clinical-radiological diagnosis and management of oral lesions and conditions and associated maxillofacial disorders.