Journal of Vaccine Research 2024, Vol.14, No.5, 231-242 http://medscipublisher.com/index.php/jvr 237 6.2 Inactivated vaccines: protection levels against omicron Inactivated vaccines, such as CoronaVac (Sinovac), have shown lower effectiveness against the Omicron variant compared to mRNA vaccines. Studies have indicated that two-dose regimens of inactivated vaccines induce low to negligible neutralizing antibodies (NAb) against Omicron (Niyomnaitham et al., 2022). However, a booster dose of an mRNA vaccine following a primary series of inactivated vaccines significantly increased the NAb titers against Omicron, suggesting that heterologous booster regimens could enhance protection (Niyomnaitham et al., 2022). A systematic review highlighted that the protection from primary vaccination with inactivated vaccines against Omicron infection is inferior to that against Delta and Alpha infections and wanes faster over time. However, primary vaccination still preserved strong protection against Omicron-associated hospitalization, severity, and death, even months after the last dose. Boosters provided more robust and longer-lasting protection against hospitalizations due to Omicron compared to the primary series alone (Paul et al., 2023). 6.3 Adenovirus vector vaccines: efficacy of the ChAdOx1 vaccine against various strains Adenovirus vector vaccines, such as ChAdOx1 (AstraZeneca), have demonstrated robust immune responses, although they elicit lower antibody responses compared to mRNA vaccines. Despite this, they are nearly as effective in preventing severe disease, likely due to the generation of immune memory cells (Fryer et al., 2023). Studies have shown that ChAdOx1 vaccination elicits a strong memory B cell response capable of recognizing Omicron subvariants BA.2 and BA.5. The second dose of ChAdOx1 boosted memory B cells that recognized variants of concern (VoC), with 37% and 39% of Wuhan-Hu-1-specific memory B cells recognizing BA.2 and BA.5, respectively (Fryer et al., 2023). A systematic review and meta-analysis found that the effectiveness of ChAdOx1 against Omicron infection was moderate, but a booster dose provided better protection against severe infection. The effectiveness of the booster dose against severe Omicron infections was 18% within three months and 37% for symptomatic infections (Pratama et al., 2022; Li, 2024). This suggests that while the primary series of ChAdOx1 provides some level of protection, booster doses are crucial for maintaining higher levels of effectiveness against emerging variants. While mRNA vaccines like BNT162b2 and Moderna have shown high effectiveness against various SARS-CoV-2 variants, including Delta and Omicron, their protection wanes over time, necessitating booster doses. Inactivated vaccines offer lower initial protection against Omicron but can be significantly enhanced with mRNA boosters. Adenovirus vector vaccines like ChAdOx1 provide robust immune memory responses, and their effectiveness can also be improved with booster doses. Regular booster vaccinations are essential to maintain high levels of protection against COVID-19 across different vaccine types and variants (Pratama et al., 2022; Thompson et al., 2022; Niyomnaitham et al., 2022; Fryer et al., 2023; Paul et al., 2023). 7 Development and Future Prospects of Next-Generation Vaccines 7.1 New vaccines targeting variants The rapid emergence of SARS-CoV-2 variants has necessitated the development of vaccines specifically targeting these new strains. Recent studies have shown that vaccines based on the ancestral spike protein may not provide sufficient protection against newer variants such as Omicron and its sub-lineages (Kang et al., 2023). To address this, researchers have developed multivalent vaccines using platforms like the Ad5/35 vector, which encode spike proteins from multiple variants. These vaccines have demonstrated the ability to induce broadly neutralizing antibodies, thereby offering enhanced protection against a range of circulating strains (Kang et al., 2023). Moreover, mRNA technology has proven to be highly adaptable for rapid vaccine development. For instance, an mRNA vaccine encoding a trimeric receptor-binding domain (RBD) fused to ferritin nanoparticles has shown robust and durable immune responses in preclinical studies. This vaccine was quickly modified to target specific variants, producing broad-spectrum neutralizing antibodies against both Alpha and Beta variants (Sun et al., 2021). Such advancements highlight the potential for mRNA vaccines to be swiftly updated to combat emerging variants.
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