virus vaccine and injection, 3D rendering
The continuous evolution of SARS-CoV-2 into new variants, each as or more virulent than the last, underscores the continued need to update our vaccine defenses against the virus. While updated vaccines work against the variant for which they were designed, the virus is rapidly evolving to become more infectious and evade our last immune defenses. This dynamic underscores the need for a universal vaccine, a potentially game-changing vaccine that could neutralize all forms of SARS-CoV-2 and even other related coronaviruses. Recent study by Peter Halfmann and colleagues from the University of Wisconsin offers promising signs that this global vaccine is on the horizon.
In the four years and several million deaths since the virus emerged in early 2020, we have seen many iterations of the COVID-19 shooting. Several companies using various methods, including mRNA, dead virus, and purified subunits, have worked with their federal governments to develop vaccines with varying efficacies. The most effective of these were the Pfizer and Moderna mRNA vaccines.
The initial Pfizer and Moderna vaccines were released in 2021 as a two-dose regimen, followed by a booster six months later. In late 2022, updated bivalent vaccines were released to target Omicron BA.4 and BA.5. Finally, at the end of 2023, they released another updated booster for Omicron XBB.1.5. The similarities between this strategy and what we see with annual flu shots are obvious: an updated booster released each year to target the current circulating strain of the virus.
Over time, the virus develops a series of mutations in the Spike protein and other genes that help evade immunity, resulting in a new variant and reduced effectiveness for the latest vaccine. The need for a universal vaccine is as clear as day, but it has yet to be achieved.
Halfmann and his colleagues attempt to fill this gap in their study Naturecreating a vaccine that neutralizes not only the many forms of SARS-CoV-2 but also similar bat coronaviruses SARS-CoV-2 and SARS-CoV in a proactive strategy to prevent future outbreaks.
Halfmann and colleagues expanded their vaccine to include elements of eight Spike proteins, namely the 614D, BA.1, BA.5, BA.2.75.2 and XBB variants of SARS-CoV-2, SARS-CoV and bat coronaviruses SHC014 and WIV1.
To maximize the universality of their vaccine, they used a Spike protein nanoparticle platform. Imagine wanting to make a salad using only ingredients from a garden. Spike proteins of a SARS-CoV-2 particle are identical, like a garden of only lettuce. The nanoparticle platform, known as MS2-SA, allows multiple Spike proteins to attach to the same base, like a garden of lettuce, tomatoes, radishes and cucumbers, allowing for a much sturdier salad.
FIGURE 1: Schematic of the attachment of various biotinylated S proteins to MS2-SA.
The nanoparticle platform can incorporate multiple spike protein antigens, allowing the development of many different multipotent vaccines or “cocktails” that provide broad protection.
By testing various combinations, they discovered a trivalent candidate with promising efficacy data.
A combination of nanoparticles, including 614D, SHC014 and Omicron XBB (shown in the image above in blue), produced a strong level of protection against not only several dominant forms of Omicron but also the bat coronaviruses SHC014 and WIV1, indicating an extended range of neutralization potential in this branch of the coronavirus lineage, namely SARS-CoV-2, SARS-CoV and some common cold coronaviruses. This combination in particular may not neutralize some coronaviruses.
Moreover, the vaccines were more than functionally effective in vitro; they protected live hamsters from various viruses. The trivalent combination of 614D, SHC014 and Omicron XBB drastically reduced the lung virus titers of BA.5 and XBB.1 infected hamsters. Similar results are seen when hamsters are infected with WIV1 or SHC014 bat coronaviruses and vaccinated with the trivalent vaccine.
There are three important takeaways from this research. First, the development of a broadly protective vaccine is crucial to ending the evolutionary game of cat and mouse with SARS-CoV-2. Halfmann and colleagues’ trivalent vaccine could be the solution.
Second, the ability of this trivalent vaccine to elicit cross-reactive neutralizing antibodies and provide full protection against various coronaviruses in animal models suggests that it could be an effective strategy for future potential coronavirus outbreaks.
Third, if this vaccine proves successful in clinical trials, similar vaccine strategies could be adapted to target other emerging viral threats beyond SARS-CoV-2 and its variants. This means we could adjust the viruses used in the formula to find something that works if wildly different viruses threaten an epidemic in the near future.
I look forward to further testing and development of this vaccine and urge that we move quickly to make it available to consumers to build another strong defense against the ongoing COVID-19 pandemic.
