Journal of Vaccine Research 2024, Vol.14, No.5, 231-242 http://medscipublisher.com/index.php/jvr 238 7.2 Potential of broad-spectrum vaccines The development of broad-spectrum vaccines is crucial for providing protection against multiple SARS-CoV-2 variants and future viral mutations. Broad-spectrum vaccines aim to induce immunity that is effective across a wide range of viral strains, reducing the need for frequent updates. One promising approach involves the use of chimeric RBD constructs from different coronaviruses. For example, a DNA vaccine encoding a dimeric RBD chimera of SARS-CoV-1 and SARS-CoV-2 variants has shown potent immunogenicity and broad-spectrum protection in preclinical models (Fan et al., 2023). This vaccine, delivered via microneedle array patches, elicited strong neutralizing antibody responses and protected mice from Omicron BA.1 challenge. Additionally, the development of polyvalent vaccines, which include antigens from multiple variants, has shown promise. A bivalent vaccine combining antigens from BA.5 and BA.2.75 variants induced broadly neutralizing antibodies and improved cross-neutralization capacity in preclinical studies (Kang et al., 2023). Such vaccines could provide a more comprehensive immune response, potentially reducing the impact of future variants. 7.3 Prospects of mRNA technology and other innovative platforms mRNA technology has revolutionized vaccine development, offering rapid and flexible solutions to emerging infectious diseases. The success of mRNA vaccines like Pfizer/BioNTech's BNT162b2 and Moderna's mRNA-1273 has demonstrated the potential of this platform to provide high levels of protection against COVID-19 (Sharif et al., 2021; Rudan et al., 2022). The ability to quickly modify mRNA sequences to target new variants makes this technology particularly valuable in the ongoing fight against SARS-CoV-2. Innovative platforms such as viral vectors and nanotechnology are also being explored for next-generation vaccines. For instance, adenoviral vector-based vaccines have shown efficacy in inducing strong immune responses and can be engineered to target multiple variants (Kang et al., 2023). Additionally, nanoparticle-based vaccines, such as those using ferritin-formed nanoparticles, have demonstrated the ability to enhance the stability and immunogenicity of vaccine antigens (Sun et al., 2021). The integration of these innovative platforms with traditional vaccine approaches could lead to the development of vaccines that are not only effective against current variants but also adaptable to future mutations. For example, the use of self-assembled nanoparticle-based trimeric RBD mRNA vaccines has shown promise in providing broad-spectrum protection and could serve as a reference for future vaccine design (Sun et al., 2021). 8 Concluding Remarks The evolution of COVID-19 vaccines has been a dynamic process, driven by the emergence of new variants that challenge the efficacy of existing vaccines. Initially, vaccines were developed based on the ancestral strain of SARS-CoV-2, which provided substantial protection against severe disease and symptomatic infection. However, as the virus evolved, new variants such as Delta and Omicron emerged, each with mutations that allowed them to partially evade the immune response elicited by these vaccines. The Omicron variant, in particular, has posed significant challenges due to its high transmissibility and numerous mutations in the spike protein. Studies have shown that while the original vaccines still offer protection against severe disease, their efficacy against symptomatic infection has decreased. This has led to the development of multivalent and bivalent vaccines designed to target multiple variants simultaneously. For instance, vaccines based on the adenovirus type 5/35 vector platform have been developed to include spike proteins from various Omicron subvariants, showing promising results in broadening immunity. The waning immunity observed over time and the continuous emergence of new variants underscore the importance of booster doses. Booster vaccinations have been shown to significantly enhance neutralizing antibody levels, thereby improving protection against both existing and emerging variants. For example, heterologous booster regimens, which combine different types of vaccines, have demonstrated superior immunogenicity compared to homologous boosters, particularly in older adults.
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