A new study published on a pre-print server has described a new subunit nanovaccine that appears to have robust immunogenicity and neutralizing activity. The researchers drew on their earlier experience of polymersomes (PS), which are self-assembled bodies formed from the block copolymer poly(ethylene glycol)-bl-poly(propylene sulfide) (PEG-PPS).
These were proved to effectively deliver antigen and adjuvant to the endosomes of dendritic cells. These are innate immune cells that present the antigens to responsive immune cells of the adaptive immune system. Within the endolysosomes, the PPS undergoes oxidation, and the PS thereby forms micelles instead, releasing the encapsulated antigen or other cargo. The result has been dendritic cell activation, a strong T cell response, and high polyclonal antibody titers. The researchers attempted to enhance the antibody response to PS-borne antigens without sacrificing the cellular immune response by modifying them in such a way that they would resemble a viral particle in form, displaying multiples of the target antigen.
The hope was that this multivalent RBD display would improve crosslinking characteristics and B cell receptor (BCR) clustering to induce higher levels of neutralizing antibodies. In this study, PS with both surface-bound RBD and encapsulated RBD were evaluated with an adjuvant monophosphoryl lipid A-encapsulated PS (MPLA PS). The researchers produced their nanovaccine candidate by conjugating spike antigens to the PS surface, using a versatile N3-PEG-PPS platform that can be adapted for any antigen. It is capable of being assembled to form PS particles with multiple functional groups on the surface that can attach the desired antigen – in this case, the spike RBD. When tested in preclinical studies, the results show that mice vaccinated with two doses of the surface-RBD display formulation developed high titers of neutralizing antibodies to SARS-CoV-2, along with strong germinal center responses indicating B cell activation and robust CD4+ and CD8+ T cell immunity.
The antibody response began less than one week from the first dose, and the highest response was with the encapsulated RBD formulation. The levels remained constant or slowly increased until the boost dose, at which point it went up by 1.3-1.6-fold.
The antibody response to the surface RBD was dominated by IgG1, compared to IgG2 and IgG3, also indicating a Th2-biased response, whereas it was more balanced with the encapsulated form. IgA antibodies were detectable in all groups that received adjuvanted vaccines, which is key to producing mucosal immunity. Neutralizing antibodies were induced by the RBD-conjugated antigen more effectively, as shown by a cell-based assay, with a high viral neutralization titer (VNT) – the at which 50% of cells survive following virus challenge. The neutralizing capacity appears to be equivalent to that of high-titer convalescent plasma.
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