Polymersomes Decorated with the SARS-CoV-2 Spike Protein Receptor-Binding Domain Elicit Robust Humoral and Cellular Immunity

Abstract

The COVID-19 pandemic underscores the need for rapid, safe, and effective vaccines. In contrast to some traditional vaccines, nanoparticle-based subunit vaccines are particularly efficient in trafficking antigens to lymph nodes, where they induce potent immune cell activation. Here, we developed a strategy to decorate the surface of oxidation-sensitive polymersomes with multiple copies of the SARS-CoV-2 spike protein receptor-binding domain (RBD) to mimic the physical form of a virus particle. We evaluated the vaccination efficacy of these surface-decorated polymersomes (RBD surf ) in mice compared to RBD-encapsulated polymersomes (RBD encap ) and unformulated RBD (RBD free ), using monophosphoryl-lipid-A-encapsulated polymersomes (MPLA PS) as an adjuvant. While all three groups produced high titers of RBD-specific IgG, only RBD surf elicited a neutralizing antibody response to SARS-CoV-2 comparable to that of human convalescent plasma. Moreover, RBD surf was the only group to significantly increase the proportion of RBD-specific germinal center B cells in the vaccination-site draining lymph nodes. Both RBD surf and RBD encap drove similarly robust CD4 + and CD8 + T cell responses that produced multiple Th1-type cytokines. We conclude that a multivalent surface display of spike RBD on polymersomes promotes a potent neutralizing antibody response to SARS-CoV-2, while both antigen formulations promote robust T cell immunity.

Shaping Neonatal Immunization by Tuning the Delivery of Synergistic Adjuvants via Nanocarriers

“…Such an approach must account for tailoring vaccines to vulnerable populations with distinct immunity. For example, receptor-binding domain (RBD) protein and MPLA can be formulated into stable, biologically active PSs and can induce robust RBD-specific humoral and polyfunctional Th1 responses in adult mice . However, adjuvantation systems such as AS01 and AS02, both consisting of MPLA and the purified plant bark extract/saponin QS21, are components of the Mosquirix (RTS,S) malaria vaccine, which has demonstrated a reduced efficacy in the pediatric setting. , …”

Shaping neonatal immunization by tuning delivery of synergistic adjuvants via nanocarriers

“…Such an approach must account for tailoring vaccines to vulnerable populations with distinct immunity. For example, receptor-binding domain (RBD) protein and MPLA can be formulated into stable, biologically active PSs, and can induce robust RBD specific humoral and polyfunctional Th1 responses in adult mice 51 . However, adjuvantation systems such as AS01 and AS02, both consisting of MPLA and the purified plant bark extract/saponin QS21, are components of the Mosquirix (RTS,S) malaria vaccine 52 , which has demonstrated reduced efficacy in the pediatric setting 52, 53 .…”

Bimodal Targeting of Human Leukocytes by Fc- and CpG-Decorated Polymersomes to Tune Immune Induction

“…The great benefit of nanoparticulate formulations is that different bioactive entities can be co-administered and displayed on the same particle scaffold. The added value of this approach has, for example, already been demonstrated by the coupling of monophosphoryl lipid A and imiquimod onto polymersomes, which resulted in the induction of immune responses against a co-delivered antigen. − In the present study, we investigated the potency and mechanism of Fc fragment- and CpG-mediated bimodal targeting in the context of polymersomes providing evidence that the simultaneous surface decoration of polymersomes with Fc fragments and CpG allows for efficient cell targeting and immune induction. This shows the potential of polymersomes as a versatile delivery system for the development of highly defined nanoparticle-based vaccines.…”