Enhanced immunogenicity of SARS-CoV-2 antigen with aluminum adjuvant and polysaccharide nucleic acid fraction of Bacillus Calmette Guerin.

Vaccine immunization strategies are crucial for eliciting vaccine-induced immune responses, particularly in immune compromised populations and older adults. In clinical practice in China, the polysaccharide nucleic acid fraction of Bacillus Calmette-Guérin (BCG-PSN) is extensively used as an immune modulatory agent. Herein, we describe a new immunization strategy using the SARS-CoV-2 antigen (original strain) with aluminum adjuvant and BCG-PSN. We evaluated whether BCG-PSN enhances humoral and cellular immune responses to the SARS-CoV-2 vaccine in K18-hACE2 and BALB/c mice by assessing antibody and germinal center (GC) responses, as well as the quantity and functionality of memory T cells in the spleen. At day 28 after the first immunization, the SARS-CoV-2 antigen with Alum, when combined with BCG-PSN, significantly elevated the levels of IgGantibodies. It significantly enhanced the spleen's GC structure, amplified the SARS-CoV-2 antigen-specific T cell response, and conferred protection to mice against the Delta variant challenge. This study provides a reference to evaluate immunization strategies for vaccines with high immunological efficacy, and the SARS-CoV-2 antigen combined with Alum and BCG-PSN enhances immunogenicity by significantly boosting cellular immune responses after vaccine administration. The study focuses on the impact of BCG-PSN on the SARS-CoV-2 antigen, examining its role in generating neutralizing antibodies (NAbs) and eliciting T cell responses.