Could β-glucans enhance the immune response to SARS-CoV-2 vaccine by inducing trained immunity and boosting neutralizing antibody production?

β-Glucans stimulate the immune system, training it to recognize and respond to antigens, which bolsters immunity, including to vaccines. The present study evaluated the capacity of β-glucans to stimulate immunity subsequent to primary vaccination for SARS-CoV-2 with ChAdOx1. Thirty-four SARS-CoV-2-non-immune men (18-49 years) were split into two groups: one receiving 500 mg of oral insoluble yeast β-glucans daily (the glucan group) and the other a placebo (the control group). The supplementation period lasted fourteen days in total, including seven days before and seven days after the initial vaccine dosage. A series of blood samples were collected at three time points: M1 (prevaccination); M2 (30 days after the first vaccination); and M3 (30 days after booster). A lateral flow immunoassay was used to qualitatively identify IgM and IgG against the virus. The levels of antigen-specific IgG anti-spike (S1), receptor-binding domain (RBD), and nucleocapsid (N) were quantified using a LEGENDplex assay. The NeutraLISA assay was used to evaluate the neutralizing antibodies (NAbs). Statistically significant results were defined as those with p < 0.05. Both groups produced similar amounts of NAbs after the first vaccination (M2). However, the glucan group had higher levels in M3, with a more uniform distribution. Furthermore, the levels of anti-S1 IgG in M2 exhibited elevated concentrations, indicating a significant positive correlation with NAbs levels obtained post-second dose (M3). In contrast, individuals who had immunity to common cold human coronaviruses (HCoVs), evidenced by the presence of IgG anti-N in M1 were associated with IgG anti-S1 only in M3, not correlated with NAbs levels. This finding indicates that cross-immunity from other HCoVs did not accelerate or direct the humoral immune response as was observed in the glucan group. Therefore, it can be inferred that the β-glucan supplementation was more effective than immunity from other HCoVs. The capacity of β-glucan to induce trained immunity (TRIM) has the potential to augment immune responses, thereby modifying antibody production in response to the vaccine stimulus. Future studies should evaluate the potential of β-glucan as an adjuvant to vaccines, especially in children, the elderly, and immunocompromised individuals. They should also assess long-term immunity and cross-protection.