Toward a Universal Covid Vaccine
(Posted on Wednesday, April 10, 2024)
This article was originally published on Forbes on 4/10/24.
The continued evolution of SARS-CoV-2 into new variants, each as or more infectious than the last, underscores the ongoing need to update our vaccine defenses against the virus. While updated vaccines work against the variant for which they are designed, the virus quickly evolves to become more infectious and evade our latest immune defenses. This dynamic underscores the need for a universal vaccine, a potential game-changer that could neutralize all forms of SARS-CoV-2 and even other related coronaviruses. A recent study by Peter Halfmann and colleagues from the University of Wisconsin offers promising indications that this universal vaccine is on the horizon.
Over the four years and many millions of deaths, since the virus emerged in early 2020, we have seen several iterations of the COVID-19 shot. Many companies using several methods, including mRNA, killed virus, and purified subunits, worked with their federal governments to develop vaccines with various 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, they released updated bivalent vaccines to target Omicron BA.4 and BA.5. Finally, in late 2023, they released another updated booster for Omicron XBB.1.5. The similarities between this strategy and what we see with the annual flu shots are evident: an updated booster released every year to target the currently circulating strain of the virus.
Over time, the virus develops a series of mutations in the Spike protein and other genes that aid in immune evasion, resulting in a new variant and reduced efficacy for the latest vaccine. The need for a universal vaccine is clear as day but has yet to be attained.
Halfmann and colleagues attempt to fill this void in their study in Nature, creating a vaccine that neutralizes not only the many forms of SARS-CoV-2 but also similar SARS-CoV-2 and SARS-CoV-like bat coronaviruses in a forward-thinking strategy to prevent future epidemics.
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 SARS-CoV-2 variants, SARS-CoV, and bat coronaviruses SHC014 and WIV1.
To maximize the universality of their vaccine, they used a Spike protein nanoparticle platform instead. Imagine wanting to make a salad using only ingredients from a garden. The Spike proteins of a SARS-CoV-2 particle are identical, like a garden with only lettuce. The nanoparticle platform, known as MS2-SA, allows many Spike proteins to be attached to the same base, like a garden with lettuce, tomatoes, radishes, and cucumbers, allowing for a much more robust 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 for the development of many differing multivalent or “cocktail” vaccines that provide broad protection.
Testing various combinations, they discovered a trivalent candidate with promising efficacy data.
A combination of nanoparticles, including 614D, SHC014, and Omicron XBB (pictured in the figure above in blue), created a robust level of protection not only various dominant forms of Omicron but also bat coronaviruses SHC014 and WIV1, indicating an extensive range of neutralization potential across this branch of coronavirus lineage, namely sarbecoviruses SARS-CoV-2, SARS-CoV, and some cold causing coronaviruses. This combination in particular may not neutralize some coronaviruses.
Furthermore, the vaccines were more than functionally efficacious in vitro; they protected live hamsters from various viruses. The trivalent combination of 614D, SHC014, and Omicron XBB drastically reduced lung virus titers of BA.5 and XBB.1-infected hamsters. Similar results are seen when the hamsters are infected with bat coronaviruses WIV1 or SHC014 and vaccinated with the trivalent vaccine.
There are three major takeaways from this research. First, developing a broadly protective vaccine is crucial to end the evolutionary game of cat and mouse with SARS-CoV-2. Halfmann and colleagues’ trivalent vaccine could be the solution.
Second, this trivalent vaccine’s ability to elicit cross-reactive neutralizing antibodies and provide complete protection against diverse coronaviruses in animal models suggests 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 being used in the formula to find something that works if wildly different viruses threaten an epidemic in the near future.
I eagerly anticipate the further testing and development of this vaccine and urge haste to bring forward its consumer availability to create another strong defense in the ongoing COVID-19 pandemic.