A Lymph Node Targeted Amphiphile Vaccine Induces Potent Cellular and Humoral Immunity to SARS-CoV-2

Abstract

The SARS-CoV-2 pandemic has led to public health, economic, and social consequences that mandate urgent development of effective vaccines to contain or eradicate infection. To that end, we evaluated a novel amphiphile (AMP) vaccine adjuvant, AMP-CpG, composed of diacyl lipid-modified CpG, admixed with the SARS-CoV-2 Spike-2 receptor binding domain protein as a candidate vaccine (ELI-005) in mice. AMP immunogens are efficiently delivered to lymph nodes, where innate and adaptive immune responses are generated. Compared to alum, AMP immunization induced >25-fold higher antigen-specific T cells which produced multiple Th1 cytokines and trafficked into lung parenchyma and respiratory secretions. Antibody responses favored Th1 isotypes (IgG2bc, IgG3) and potently neutralized Spike-2-ACE2 receptor binding, with titers 265-fold higher than the natural immune response from convalescent COVID-19 patients; responses were maintained despite 10-fold dose-reduction in Spike antigen. Both cellular and humoral immune responses were preserved in aged mice. These advantages merit clinical translation to SARS-CoV-2 and other protein subunit vaccines.

Non-viral COVID-19 vaccine delivery systems

“…Use of an amphipathic component to deliver peptides or adjuvants through interaction with albumin post-injection followed by LN draining has proven to significantly enhance vaccine efficacies [ 133 ]. Elicio Therapeutics has recently tested amphiphile-bound CpG admixed with SARS-CoV-2 RBD protein to vaccinate mice, which resulted in 25-fold higher antigen-specific T cell responses and Th1 favored antibody responses (IgG2bc and IgG3) [ 134 ]. In another study, hydroxy-poly(ethylene glycol)-based cylindrical-shaped nanoparticles were used to deliver a model antigen, ovalbumin, which facilitated antigen draining to LN upon SC injection in mice [ 135 ].…”

Biomaterial-based immunoengineering to fight COVID-19 and infectious diseases

“…Elicio Therapeutics repurposed this type of platform and showed an improvement in SARS-CoV-2-specific cellular and humoral immune responses in mice. 59 Optimal activation of humoral immune responses also relies on appropriate antigen presentation to B cells. 60 To enhance B cell receptor engagement, lipid-based particles can be used as the base platform with the addition of MPLA as an immunostimulatory adjuvant.…”