Modular capsid decoration boosts adenovirus vaccine-induced humoral immunity against SARS-CoV-2

The research paper presents a novel strategy for enhancing the effectiveness of adenovirus vector vaccines in inducing humoral immunity against displayed antigens. The authors introduce a system of decorating adenovirus capsids with antigens using a protein superglue technology, which increases immunogenicity without compromising vector infectivity. By covalently attaching ligands on the capsid surface, the study demonstrates enhanced immune responses and neutralization titers against the receptor-binding domain of the SARS-CoV-2 spike protein. The capsid decoration approach is proposed as a promising method to boost the efficacy and boostability of adenovirus-based vaccines and therapeutics.

Adenovirus vector vaccines have been successful in responding to the COVID-19 pandemic, yet there are limitations in boosting vaccine-specific antibody responses compared to other technologies. The study presents a system enabling modular decoration of adenovirus capsids with antigens. Ligand attachment using a protein superglue allows rapid and spontaneous covalent bonding, resulting in efficient coverage of the capsid surface while retaining vector infectivity. Capsid decoration shields particles from vector neutralizing antibodies and significantly enhances humoral immunity against displayed antigens.

This capsid decoration technology showcases potential for improving vaccine effectiveness, particularly in generating robust humoral and cellular immune responses. The study highlights that the approach of coupling antigens to adenovirus capsids can lead to potent neutralizing antibody responses against target antigens, thereby enhancing the overall efficacy and boostability of adenovirus-based vaccines and therapeutics.

The research paper discusses a novel strategy for enhancing the efficacy of adenovirus vector vaccines in inducing humoral immunity against antigens, specifically the receptor-binding domain of the SARS-CoV-2 spike protein. The method involves decorating adenovirus capsids with antigens using a protein superglue technology, which leads to improved immune responses and neutralization titers without compromising the vector's infectivity. The study demonstrates the covalent attachment of ligands on the capsid surface, resulting in increased immunogenicity of the vaccine. By enhancing capsid decoration, the approach shows promise in boosting the effectiveness of adenovirus-based vaccines and therapeutics. Various experiments were conducted, including assessing ligand coupling efficiency, evaluating vector neutralization against monoclonal antibodies and serum samples, measuring endogenous human ACE2 expression, and analyzing vector transduction in cells. Additional experiments involved evaluating IFN-g responses, IgG ELISA, and SARS-CoV-2 pseudovirus neutralization assays. Cryo-EM analysis was performed to visualize the Ad-DogTag and Ad-DogTag:DogCatcher-RBD samples, providing insights into capsid protein interactions. Statistical analyses were conducted to support the findings presented in the study. The paper concludes by acknowledging the researchers' contributions, funding sources, and any potential conflicts of interest among the authors.