Vaccine-induced antibody response to SARS-CoV-2 Omicron variant in patients with B cell malignancies with and without active B cell-targeted therapy

Since the onset of the coronavirus disease 2019 (COVID-19) pandemic, the causal agent, i.e., severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has evolved via mutations. Although several SARS-CoV-2 variants circulate at a given time, at present, the Omicron (B.1.1.529) variant is the dominant circulating variant globally.

Background

Researchers have characterized the Omicron strain and observed thirty mutations in the Spike (S) protein and fifteen mutations in the receptor-binding domain (RBD), compared to the original SARS-CoV-2 strain. Owing to these mutations, the Omicron strain is highly contagious and can evade immune responses elicited via vaccination as well as natural infection. Several studies have shown that healthy and vaccinated individuals are sufficiently protected from severe infection. However, the level of vaccine-induced protection in immunocompromised individuals (e.g., cancer patients) is not well documented.

As patients with hematological malignancies are at a higher risk of death from COVID-19 infection compared to patients with a solid tumor, it is imperative to understand the level of protection generated after COVID-19 vaccination in this group of people. Several studies have evaluated the impact of the third dose (booster) of the mRNA vaccine in patients with cancer and organ transplant and indicated that booster vaccination has augmented antibody responses in this group.

Previous studies have indicated that booster vaccination can augment neutralizing antibodies against SARS-CoV-2, including the Omicron variant, in healthy individuals and solid tumor patients. Very little evidence is available regarding the effectiveness of COVID-19 vaccination in highly immune-compromised patients, particularly those with B cell malignancies and undergoing active therapy.

Scientists have stated that immune impairment could be extremely alarming for a patient with chronic lymphocytic leukemia (CLL) and non-Hodgkin’s lymphoma (NHL). Previous studies have reported that CLL and NHL patients undergoing B cell-targeted therapies exhibited impaired vaccine-mediated antibody responses. There is a gap in research regarding the impact of booster vaccination on antibody levels in patients with or without active B cell-targeted therapy. 

A new study

In a new study published on medRxiv* preprint server, researchers have determined the effect of booster immunization on the levels of antibodies generated, against SARS-CoV-2 variants, including the Omicron strain, in cancer patients with or without active B cell-targeted therapy. Additionally, scientists have also evaluated the degree to which B cell-targeted therapies impair de novo and preexisting antibody-mediated immunity.

In this study, scientists obtained serum samples from cancer patients who participated in the SIIREN study (The COVID-19 Vaccine Study of Infections and Immune REspoNse) at The Ohio State University Comprehensive Cancer Center. All patients were diagnosed with B cell malignancies (e.g., CLL and NHL) and received mRNA-based booster vaccination. Researchers collected serum samples pre-and post- booster mRNA vaccination. Clinical information of the patients (age, sex, race, cancer diagnosis, and therapy status), and COVID-19 mRNA vaccine-related information, were collected from the internal electronic medical record database.

Key findings

The authors observed considerable heterogeneity in antibody responses following booster vaccination in the study cohort. Patients who were not under active cancer therapy exhibited significant enhancement in antibodies post-COVID-19 booster vaccination. In contrast, several patients who were on active therapy remained seronegative even after receiving two doses of COVID-19 vaccine (primary vaccination) and booster. 

Among all seropositive patients, a robust correlation between antibodies against the previous SARS-CoV-2 strains and the Omicron variant was observed. This result implies that the Omicron variant is not sufficiently antigenically distinct to evade all vaccine-mediated antibody responses. However, similar to individuals with a solid tumor, scientists revealed a reduction in the neutralizing antibody level against Omicron, relative to the original strain, in the study cohort.

Consistent with previous reports, the current study exhibited that B cell-targeted therapies are associated with decreased antibody responses after primary vaccination. In addition, a considerable number of individuals with B cell malignancies remained seronegative after booster vaccination. Even though booster vaccination was beneficial to some patients with B cell malignancies, more research is required to determine if post-booster seronegative patients may experience some benefits from their vaccination status.

Scientists stated that irrespective of an individual with B cell malignancies being treated with active therapy or remaining seronegative post-vaccination, normal levels of preexisting antibodies against previous endemic viruses (e.g., influenza) were observed. Previous studies using mice and macaques reported that preexisting antibodies generated via vaccination or natural infection were preserved even after anti-CD20 mAb treatment. The authors revealed that B cell-targeted therapies have minimum impact on long-lived plasma cells (LLPCs). Scientists suggested that vaccination before B cell-targeted therapy could play an important role in providing long impact.

Conclusion

One of the limitations of this study is that while active therapy has been linked with reduced antibody responses, the authors could not confirm if it is the true reason for the reduction. Another limitation of the study is the small sample size. Scientists revealed that individuals with B cell malignancy undergoing active therapies exhibit disproportional vulnerability to new infections owing to their inability to produce de novo antibody 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

Dr. Priyom Bose

Priyom holds a Ph.D. in Plant Biology and Biotechnology from the University of Madras, India. She is an active researcher and an experienced science writer. Priyom has also co-authored several original research articles that have been published in reputed peer-reviewed journals. She is also an avid reader and an amateur photographer.