Chinese authors investigated immune responses to a prolonged course of booster vaccine with the recombinant receptor binding domain (RBD) in a Balb/c mouse model. The results have shown that prolonged SARS-CoV-2 RBD booster vaccination promotes humoral and cellular immune tolerance in mice.
From the end of 2021 the Omicron variant of SARS-CoV-2 has overtaken the global dominance. Epidemiological studies have revealed substantial levels of vaccine breakthrough infections and reinfections. Serum protection after one booster vaccination has been shown to decrease over time, which rendered the immunized individuals susceptible to continuous risk from newly emerged SARS-CoV-2 variants. One of the major concerns associated with continuous immunization with booster vaccines is the relatively limited response window to the same stimuli. Previous studies have shown that repeated administration of foreign antigens can induce immune tolerance, which is manifested in an unresponsiveness of the immune system, in an inability or low efficiency to produce antigen-specific antibodies and to activate effector T cells.
About the study
A new study from Chinese authors evaluated immune responses to a prolonged course of booster vaccine with the recombinant receptor binding domain (RBD) in a Balb/c mouse model. They compared the humoral and cellular immune responses of an extended course of recombinant RBD vaccine boosters with those of the conventional immunization strategy.
The results showed that prolonged vaccination promoted the development of a prominent adaptive immune tolerance and profoundly impaired the immune response established by conventional course. This has been demonstrated by significant reductions in antigen specific antibody and T-cell response, loss of immune memory and a form of immunosuppressive microenvironment.
The extended immunization has completely reduced the amount and neutralizing efficiency of serum RBD-specific antibodies, and has also shortened the long-term humoral memory. This was associated with a significantly lower number of active B cells detected within the germinal center in mice in the extended immunization group compared to those in the conventional immunization group.
In addition, the results showed that prolonged immunization reduced the functional responses of CD4+ and CD8+T cells, and restricted the population of memory T cells. Extended immunization inhibited the activation of CD4+T cell immune responses and inhibited CD8+ T cell-mediated immune response. Prolonged administration of RBD booster vaccines increased the levels of PD-1 and LAG-3, accompanied by a significant reduction in the memory CD8+T cells. The authors emphasized the particular importance of these results because the response of these cells plays a predominant role in the effective response against newly emerged SARS-CoV-2 variants.
The findings also indicated that over-vaccination can generate an immunosuppression micro-environment that is also an important facilitator of immune tolerance. The percentage of CD25+Foxp3+CD4+ Treg cells and the level of cytokine IL-10 were upregulated after prolonged administration of RBD booster vaccines. This can result in reduced activation and differentiation of B cells on antigen stimulation, as well as functional inhibition of antigen-presenting cells and a consequent decrease in activation of CD8+T cells.
The results of humoral and cellular immune tolerance in mice in the extended immunization group led the authors to speculate that over-vaccination could have a serious impact on the protective immune efficacy established by conventional SARS-CoV-2 immunization, and likely increase the severity of the disease in new COVID-19 patients or in those with reinfections.
The researchers concluded that their results provided crucial evidence that the repetitive administration of RBD booster vaccination promotes humoral and cellular immune tolerance in mice. This may have a negative impact on the immune response established by conventional vaccination course and promote adaptive immune tolerance.
This article was published in the scientific journal iScience.
Gao F-X et al. Extended SARS-CoV-2 RBD booster vaccination induces humoral and cellular immune tolerance in mice. iScience 25, 105479, December 22, 2022. (Open Access) https://www.sciencedirect.com/science/article/pii/S2589004222017515