A Novel Polymer Nanoparticle Polydimethyl Diallyl Ammonium Chloride as An Adjuvant Enhances the Immune Response of SARS‐CoV‐2 Subunit Vaccine

Abstract The Coronavirus Disease 2019 (COVID‐19) pandemic caused by SARS‐CoV‐2 has a significant impact on global health and the economy. It has underscored the urgent need for a stable, easily produced and effective vaccine. This study presents a novel approach using SARS‐CoV‐2 spike (S) protein‐conjugated nanoparticles (NPs) in combination with cyclic GMP‐AMP (cGAMP) (S‐NPs‐cGAMP) as a subunit vaccine. When mice are immunized, the antiserum of S‐NPs‐cGAMP group exhibits a 16‐fold increase in neutralizing activity against a pseudovirus, compared to S protein group. Additionally, S‐NPs‐cGAMP induces even higher levels of neutralizing antibodies. Remarkably, the vaccine also triggers a robust humoral immune response, as evidenced by a notable elevation in virus‐specific IgG and IgM antibodies. Furthermore, after 42 days of immunization, there is an observed increase in specific immune cell populations in the spleen. CD3 + CD4 + and CD3 + CD8 + T lymphocytes, as well as B220 + CD19 + and CD3 − CD49b + NK lymphocytes, show an upward trend, indicating a positive cellular immune response. Moreover, the S‐NPs‐cGAMP demonstrates promising results against the Delta strain and exhibits good cross‐neutralization potential against other variants. These findings suggest that pDMDAAC NPs is potential adjuvant and could serve as a versatile platform for future vaccine development.