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The Evolution of Vaccines in SARS-CoV-2 Viral Chase
In late 2019, a new coronavirus named SARS-CoV-2 sparked a global crisis with COVID-19. Swiftly, scientists rolled out vaccines like mRNA-1273 and BNT162b2, boasting over 90% effectiveness. These jabs, based on the original Wuhan virus’s blueprint, have slashed severe illness and death rates significantly. Yet, as the virus mutates, creating variants like Beta, Delta, and Omicron, these vaccines’ power wanes. The Omicron variant, particularly sneaky, has led to updated shots. Still, they struggle against Omicron’s offspring, with neutralizing antibodies dipping compared to the Wuhan strain. The virus’s spike protein, key to its neutralization, keeps changing, dodging vaccine-induced defences by generating new mutations. This arms race has scientists hustling to craft next-gen vaccines for broader, longer-lasting defence against this shapeshifting foe, aiming to curb the spread even among the vaccinated. It’s a global sprint, blending old knowledge with new discoveries, to outpace a virus that’s always one step ahead.
Picture a vaccine akin to a train, where the engine is the core SARS-CoV-2 Wuhan S1 sequence and the cars are the Receptor Binding Domains (RBDs) of various variants of concern (VOCs). The RBD is a critical region within the spike protein of the virus and it act as the ‘key’ by interacting with the host cell’s Angiotensin-converting enzyme 2 (ACE2) receptor, facilitating viral attachment and entry. This innovative “train model” introduced by Ravendra Garg et al. in April 2024 employs linkers where the RBDs are connected to the Wuhan S1 protein via a glycine-serine flexible linker sequence. This design has demonstrated broad protection against SARS-CoV-2 VOCs in the Syrian golden hamster model. It has been designed and deemed to be adaptable, allowing for the swift exchange of components—much like swapping out train cars—to combat various virus variants. The core of the vaccine, the “train engine,” remains constant, which is the Wuhan S1 antigen, ensuring a stable manufacturing process. The scientists cleverly engineered vaccine proteins named VIDO4296, VIDO4304, and VIDO4372 resembling the virus’s spike, linking them with a glycine-serine flexible chain. They had replaced the deltaRBD part in VIDO4296 with omicronRBD for the generation of VIDO4304 subunit, where both of them are linked with a seven amino acid glycine-serine linker sequence. Similarly for the VIDO4372, they merged Beta and Omicron RBDs with the same linker sequence.
Remarkably, when these proteins were glycosylated and combined with anadjuvant, they demonstrated potential in preventing the disease in hamster models by enhancing their stability and immunogenicity. This approach not only builds upon first-generation vaccines, currently in clinical trials, but also offers a versatile platform that can be swiftly updated to combat emerging SARS-CoV-2 VOCs and potentially other beta-coronaviruses. It’s a scientific leap towards a more resilient defence against the evolving threat of COVID-19.
The VIDO4296 vaccine, administered twice intramuscularly to hamsters, showed promising results against various strains of SARS-CoV-2. Post-vaccination, these animals were exposed to the Omicron, Delta, and Beta variants. The vaccinated group experienced minimal weight loss and quickly regained it, indicating health recovery. Notably, their blood contained high levels of antibodies capable of neutralizing the Delta variant, a sign of strong immune response. In contrast, control animals showed delayed weight gain and lacked these antibodies. Moreover, the vaccine significantly reduced virus levels in the nasal passages, highlighting its potential to curb transmission. Hamsters immunized with VIDO4372 also produced high anti-S1 antibody responses, whereas hamsters immunized with VIDO4304 demonstrated strong neutralizing antibodies against Omicron and Delta variants. In animal models, the vaccines derived from this platform have demonstrated effectiveness, evoking a strong antibody response comprising both neutralizing and binding antibodies and these reactions persisted 48 days after the first immunization and continued to be high even after the virus was exposed. Furthermore, by day 5 post-infection, the majority of the vaccinated animals had no detectable virus in their respiratory tracts, which showed much decreased viral titers. This suggests that these vaccinations may provide wide protection against several forms of SARS-CoV-2 that are of concern (VOCs). The versatility of the platform is further highlighted by its ability to maintain a consistent upstream and downstream process, even when the antigenic components are altered to match circulating strains.
The stability of these new vaccines was tracked over a 13-months period at refrigerator temperatures (2-8°C). Remarkably, VIDO4296 preserved all antigen integrity, and VIDO4304 and VIDO4372 displayed 50–75% integrity. These vaccines may be more affordable to make than mRNA vaccines due to their stability, no significant alterations in critical properties and the use of easily accessible adjuvants. Moreover, these subunit vaccinations do not need to be stored at extremely low temperatures, which makes distribution logistics easier and less expensive, especially in environments with limited resources. The “train model” platform’s architecture thus allows for quick adaptability to new VOCs, which may allow for a prompt reaction to emerging dangers without requiring significant changes to the production process.
While the study focused on the humoral immune response, the scientists acknowledge the importance of assessing cell-mediated immunity, which they plan to explore as more reagents become available for their animal models. The preliminary data, however, is promising, showing that the vaccine candidates can induce protective levels of neutralizing antibodies and improve clinical outcomes. The future bar is quite high with the aim to harness this platform’s full potential in order to create vaccines that can provide broad protection against a range of zoonotic pathogens.
Link to the original post: Ravendra Garg et al., (2024). Vaccine,
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