Development of Next Generation Vaccines against SARS-CoV-2 and Variants of Concern

Abstract

SARS-CoV-2 has caused the COVID-19 pandemic, with over 673 million infections and 6.85 million deaths globally. Novel mRNA and viral-vectored vaccines were developed and licensed for global immunizations under emergency approval. They have demonstrated good safety and high protective efficacy against the SARS-CoV-2 Wuhan strain. However, the emergence of highly infectious and transmissible variants of concern (VOCs) such as Omicron was associated with considerable reductions in the protective efficacy of the current vaccines. The development of next-generation vaccines that could confer broad protection against both the SARS-CoV-2 Wuhan strain and VOCs is urgently needed. A bivalent mRNA vaccine encoding the Spike proteins of both the SARS-CoV-2 Wuhan strain and the Omicron variant has been constructed and approved by the US FDA. However, mRNA vaccines are associated with instability and require an extremely low temperature (−80 °C) for storage and transportation. They also require complex synthesis and multiple chromatographic purifications. Peptide-based next-generation vaccines could be developed by relying on in silico predictions to identify peptides specifying highly conserved B, CD4+ and CD8+ T cell epitopes to elicit broad and long-lasting immune protection. These epitopes were validated in animal models and in early phase clinical trials to demonstrate immunogenicity and safety. Next-generation peptide vaccine formulations could be developed to incorporate only naked peptides, but they are costly to synthesize and production would generate extensive chemical waste. Continual production of recombinant peptides specifying immunogenic B and T cell epitopes could be achieved in hosts such as E. coli or yeast. However, recombinant protein/peptide vaccines require purification before administration. The DNA vaccine might serve as the most effective next-generation vaccine for low-income countries, since it does not require an extremely low temperature for storage or need extensive chromatographic purification. The construction of recombinant plasmids carrying genes specifying highly conserved B and T cell epitopes meant that vaccine candidates representing highly conserved antigenic regions could be rapidly developed. Poor immunogenicity of DNA vaccines could be overcome by the incorporation of chemical or molecular adjuvants and the development of nanoparticles for effective delivery.

Enhanced Immunogenicity and Protective Effects against SARS-CoV-2 Following Immunization with a Recombinant RBD-IgG Chimeric Protein

“…The impact of the COVID-19 pandemic promoted enormous investments in the development of vaccine candidates and huge revenues for companies capable of obtaining approval for their use in humans, particularly those based on mRNA and adenovirus-vectorized formulations [3,35]. Nonetheless, the global need for effective and safe vaccines capable of coping with emerging SARS-CoV-2 variants and other potential pandemic-level infectious agents demands continuous research efforts that could lead to new formulations and technologies [36]. In this study, we evaluated an experimental approach capable of improving the performance of subunit vaccines based on recombinant proteins.…”

Molecular Mimicry and HLA Polymorphisms May Drive Autoimmunity in Recipients of the BNT-162b2 mRNA Vaccine: A Computational Analysis

“…Finally, this analysis focused on the FASTA protein sequence of the vaccine BNT-162b2, which encodes the wild-type spike protein of SARS-CoV-2. Due to the emergence of SARS-CoV-2 variants and mutations in the viral spike gene, research is now shifting to the formulation of next-generation vaccines that can provide broader protection against both the Wuhan strain of SARS-CoV-2 and other variants of concern (VOCs) [ 49 ]. The presence of epitopes in these new formulations able to interact with specific HLA alleles and favor the onset of autoimmune phenomena should be investigated.…”

The Promising Potential of Reverse Vaccinology-Based Next-Generation Vaccine Development over Conventional Vaccines against Antibiotic-Resistant Bacteria

“…To improve immunogenicity, DNA vaccines often require the use of adjuvants, which can increase the immune response but may also introduce additional complexities and potential side effects [ 76 ]. Furthermore, the administration of DNA vaccines typically requires a medical device like the use of an electroporator that can deliver electric pulses to facilitate the uptake of DNA by cells [ 77 ]. This requirement may limit the accessibility and widespread use of DNA vaccines, particularly in resource-limited settings lacking such specialized equipment.…”