COVID vaccines induce memory B and T cells in primary antibody deficient patients

To date, the ongoing coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has claimed almost 6.4 million lives worldwide. Several COVID-19 vaccines developed by Pfizer-BioNTech (BNT162b2), Moderna (mRNA-1273), and Johnson & Johnson (Ad26.COV2.S) have received emergency use approval from global regulatory bodies, such as the United States Food and Drug Administration (FDA).

Study: SARS-CoV-2 booster vaccination rescues attenuated IgG1 memory B cell response in primary antibody deficiency patients. Image Credit: Vadym Pastuck / Shutterstock.com

Background

Previous studies have shown that COVID-19 vaccines effectively reduce the incidence of SARS-CoV-2 infection. However, these studies have further reported a decline of SARS-CoV-2-specific antibody titers over time. Nevertheless, cellular immune responses have been detected six months after completing two doses of the COVID-19 vaccination regime.

To address waning antibody titers, researchers at Washington University School of Medicine have strategized the administration of messenger ribonucleic acid (mRNA) booster vaccine doses, which significantly increased antibody titers. These neutralizing antibodies were found to be effective against the SARS-CoV-2 Omicron variant (B.1.1.529) that can escape immune responses induced after primary vaccination.

Some individuals with primary and secondary immunodeficiencies are not able to elicit an immune response and, as a result, are at an increased risk of severe COVID-19, which can even lead to death. Typically, these patients have an impaired SARS-CoV-2-specific antibody response after the two-dose regimens of primary COVID-19 vaccination.

The U.S. Centers for Disease Control and Prevention (CDC) has recommended that such immunosuppressed patients receive a third vaccine dose, followed by a fourth dose three months from receiving their third dose.

Previous studies have shown that these COVID-19 booster doses enhance the production of SARS-CoV-2-specific antibody responses in immunocompromised individuals. Adults with primary antibody deficiency (PAD) syndromes are unable to trigger antibody responses following vaccination or natural infection. Patients with PAD also exhibit common variable immunodeficiency (CVID), hypogammaglobulinemia, or specific-antibody deficiency. 

The etiology of PAD syndromes is not well understood in most patients. Studies have shown that individuals with PAD syndromes are at an elevated risk of severe and recurrent infections, cancer, autoimmunity, and allergic diseases.

In most cases, individuals with PAD syndromes are subjected to subcutaneous or intravenous immunoglobulin replacement therapy every one to four weeks. This is performed as a precautionary measure to reduce the incidence of an infection and prevent severe symptoms.

About the study

A recent study published on the medRxiv* preprint server provides a prospective analysis based on the SARS-CoV-2-specific B- and T-cell response post-COVID-19 primary and booster vaccination in PAD patients.

Adult patients with PAD syndromes were included in the study cohort. Each patient was categorized based on vaccination status.

The entry criteria required each patient to receive the first dose of the COVID-19 vaccine within 14 days of enrollment. After 28 days of the first dose, each candidate should have received the second dose of an mRNA or adenoviral-vector vaccine.

Participants with a history of human immunodeficiency virus (HIV) infection, cancer, or previous immunosuppressive treatment were excluded from the study cohort.

Taken together, thirty adults, including 27 females and three males with PAD syndromes, participated in the current study. The average age of the candidates was 48.4 years old. Immunocompetent healthy donors constituted the control group.

Study findings

SARS-CoV-2 vaccination was positively associated with the production of long-lived memory B- and CD4+ T-cell responses in the study cohort, with the extent of immune responses comparable to healthy donors. Importantly, the SARS-CoV-2-specific memory B-cell response was associated with neutralizing antibody titers that were effective against the Omicron variant following COVID-19 booster vaccination.

In the study cohort, only four candidates did not generate spike-specific memory B-cell responses after COVID-19 vaccination. These individuals exhibited a lower concentration of memory B-cells and activated B-cells as compared to most participants in the cohort. This indicates that memory B- and T-cells are strongly associated with long-term protective immunity in individuals with PAD syndromes.

Following primary vaccination of COVID-19-naïve PAD patients, reduced immunoglobulin G1 (IgG1) antibodies associated with SARS-CoV-2-specific memory B-cells were observed. These cells exhibited errored CD11c expression with a positive correlation between the percentage of spike-specific CD11c+ and IgG1+ cells after vaccination. Following booster vaccination, the defect in IgG1 class-switching in some PAD patients was restored.

Taken together, SARS-CoV-2 vaccination was found to initiate both a conventional and double negative memory B-cell response in most PAD patients that was persistent for at least 150 days after primary vaccination.

Conclusions

The current study reported most individuals with PAD syndromes produced a memory B- and T-cell response, which was similar to the immune response in healthy groups, following the primary vaccination regimen. Thus, the administration of COVID-19 booster doses further improved B- and T-cell responses, which was found to be effective against the Omicron variant as well.

The study findings provide an important insight related to the capacity of PAD patients in producing memory B- and T-cells, which provides protection against SARS-CoV-2 infection.

*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.