SARS-CoV-2 booster vaccination rescues attenuated IgG1 memory B cell response in primary antibody deficiency patients

Abstract

BackgroundAlthough SARS-CoV-2 vaccines have proven effective in eliciting a protective immune response in healthy individuals, their ability to induce a durable immune response in immunocompromised individuals remains poorly understood. Primary antibody deficiency (PAD) syndromes are among the most common primary immunodeficiency disorders in adults and are characterized by hypogammaglobulinemia and impaired ability to mount robust antibody responses following infection or vaccination.MethodsHere, we present an analysis of both the B and T cell response in a prospective cohort of 30 individuals with PAD up to 150 days following initial COVID-19 vaccination and 150 days post mRNA booster vaccination.ResultsAfter the primary vaccination series, many of the individuals with PAD syndromes mounted SARS-CoV-2 specific memory B and CD4+ T cell responses that overall were comparable to healthy individuals. Nonetheless, individuals with PAD syndromes had reduced IgG1+ and CD11c+ memory B cell responses following the primary vaccination series, with the defect in IgG1 class-switching rescued following mRNA booster doses. Boosting also elicited an increase in the SARS-CoV-2-specific B and T cell response and the development of Omicron-specific memory B cells in COVID-19-naïve PAD patients. Individuals that lacked detectable B cell responses following primary vaccination did not benefit from booster vaccination.ConclusionTogether, these data indicate that SARS-CoV-2 vaccines elicit memory B and T cells in most PAD patients and highlights the importance of booster vaccination in immunodeficient individuals.

An Overview of the Immune Response to COVID-19 Vaccination and Strategies to Boost SARS-CoV-2 Immunity in People with Inborn Errors of Immunity

“…However, other studies found little to no correlation between B-cell measurements and humoral response [97,129], likely due to patients receiving IgRT, where antibodies from product are indistinguishable from vaccine-induced antibodies. As with the T-cell response, Lin et al found a similar effect of a third vaccine dose increasing SARS-CoV-2-specific B-cell responses [87]. The previously mentioned individual with SASH3 deficiency had marked B-cell lymphopenia and reduced switched Bmem cells [129].…”

“…Finally, to date assessments of vaccine responses in IEI patients have only been published up to 3-4 doses of COVID-19 vaccine [73,79,84,87,91,93,120]. While this has provided critical information on early post-vaccination immune responses, immune deficient individuals were recommended to receive boosters every 3-6 months.…”

“…This is important because otherwise, known age-related changes in the immune system would confound the results of each study. The published study designs varied from observational [71,77,[83][84][85][86][87][88][89][90][91][92][93][94][95][96] to interventional studies and clinical trials [80,82,83,97,98]. Furthermore, humoral responses were reported by seroconversion, antibody concentration/titers, and, in some cases, virus neutralization/pseudo-neutralization capacity (Figure 3 and Table 2).…”

“…The COV-AD study follow-up found that receipt of heterologous vaccines by infection-naïve IEI individuals was associated with a significantly higher likelihood of T-cell response generation, compared to homogenous boosting [73]. Lin et al found that a third dose increased the amount of SARS-CoV-2-specific CD4 + and CD8 + T-cells generated [87], and Goda et al were able to demonstrate a 30% increase in T-cell activity after a third dose of Comirnaty following two ChAdOx1 n CoV-19 in individuals with CVID [120].…”

Causal association of immune cells and endometritis: a Mendelian randomization study

“…The identi cation of switched memory B cells, characterized by increased absolute counts and CD19 expression, as protective factors (OR < 1) indicates their possible involvement in a bene cial immune response against endometritis. Switched memory B cells are known for their ability to rapidly produce speci c antibodies upon reexposure to antigens [15] , suggesting that a higher presence of these cells might enhance the body's capability to ght off infections associated with endometritis. Additionally, the protective association indicated by increased CD20 expression on IgD + CD38-unswitched memory B cells and a higher percentage of switched memory B cells among lymphocytes further supports the idea that an effective B cell-mediated immune response is crucial in safeguarding against endometritis.…”