Peptide delivery of a multivalent mRNA SARS-CoV-2 vaccine

Lipid nanoparticles (LNP) have been instrumental in the success of mRNA vaccines and have opened up the field to a new wave of therapeutics. However, what is ahead beyond the LNP? The approach herein used a nano-particle containing a blend of Spike, Membrane and Envelope antigens complexed for the first time with the RALA peptide (RALA-SME). The physicochemical characteristics and functionality of RALA-SME were assessed. With >99% encapsulation, RALA-SME was administered via intradermal injection in vivo, and all three antigen-specific IgG antibodies were highly significant. The IgG2a:IgG1 ratio were all >1.2, indicating a robust T(H)1 response, and this was further confirmed with the T-Cell response in mice. A complete safety panel of markers from mice were all within normal range, supported by safety data in hamsters. Vaccination of Syrian Golden hamsters with RALA-SME derivatives produced functional antibodies capable of neutralising SARS-CoV-2 from both Wuhan-Hu-1 and Omicron BA.1 lineages after two doses. Antibody levels increased over the study period and provided protection from disease-specific weight loss, with inhibition of viral migration down the respiratory tract. This peptide technology enables the flexibility to interchange and add antigens as required, which is essential for the next generation of adaptable mRNA vaccines.

Automated summary

Lipid nanoparticles (LNP) have played a crucial role in the success of mRNA vaccines and have opened up new opportunities for therapeutics. This study investigated the use of RALA-SME nanoparticles, which contained a blend of Spike, Membrane, and Envelope antigens, for immunization. The results showed that RALA-SME induced a robust immune response, with highly significant antigen-specific antibodies and T-cell response. Immunization with RALA-SME derivatives in Syrian Golden hamsters resulted in the production of functional antibodies capable of neutralizing SARS-CoV-2 from different lineages, providing protection against disease.