Preventing the Next Epidemic: The Role of Vaccines and Antivirals

As the world officially declared the end of the COVID-19 pandemic just a few months ago, it is crucial to contemplate the measures that can be implemented to prevent the next pandemic. While protective measures such as masks, social distancing, and quarantine are essential, they are not a long-term solution. It is only a matter of time before such a virus spreads globally, becoming a permanent fixture in our society. Thus, it is imperative to focus on the research and development (RD) of vaccines and antivirals to mitigate the devastating impacts of future pandemics.

The Importance of Vaccines and Antivirals

Vaccines and antivirals are our most reliable tools in the fight against viral pandemics. Historically, vaccines have played a critical role in eradicating diseases such as smallpox, measles, and polio. During the ongoing COVID-19 pandemic, the rapid development and deployment of vaccines, especially mRNA vaccines, have significantly reduced the disease burden. The inventors of mRNA vaccines were awarded the Nobel Prize, highlighting the critical importance of these vaccines.

Developing a vaccine against a newly emerged virus presents unique challenges. Traditional methods involve growing and inactivating or attenuating the virus in cell cultures. This process is time-consuming and not feasible in the context of pandemics, which require rapid and effective interventions. However, mRNA vaccines offer a promising alternative. mRNA vaccines only carry a piece of viral genetic code and do not pose a risk of infection. They can trigger a robust immune response by expressing viral antigens in the human body, making them ideal for use in emergency situations.

Antivirals: A Backup Strategy

Antivirals include small molecules that inhibit viral replication enzymes and monoclonal antibodies that block the engagement between viral spikes and cell receptors. While the development of antivirals is less mature compared to vaccines, they offer significant potential. Antivirals can serve as a 'backup' to vaccines, further minimizing the disease burden and reducing the spread of the virus. For example, Paxlovid, a protease inhibitor, is effective against SARS, MERS, and COVID-19, making it useful for future coronavirus outbreaks.

Antivirals have a broader applicability than vaccines because they target conserved viral enzymes. For instance, neuraminidase inhibitors (NAi) and cap-dependent endonuclease inhibitors (CENi) have cross-reactivity against various RNA viruses. While both NAi and CENi target viral release and mRNA synthesis, respectively, CENi offers greater strategic value for pandemic preparedness. The CDC has identified viruses like coronavirus, avian flu, Ebola, and Nipah as high-risk due to their pandemic potential. Developing antivirals against these high-strategic-value targets could significantly improve our ability to respond to future epidemics.

Challenges in Antiviral Research

Despite their potential, antivirals face several challenges. Firstly, viruses have diverse replication strategies, making it difficult to develop antivirals that are broadly effective. For example, many viruses encode their own DNA or RNA polymerases, which share similar structures and mechanisms. This shared similarity can lead to cross-reactivity in antivirals like tenofovir, which is effective against HIV and hepatitis B. Similarly, remdesivir has shown efficacy against a wide range of RNA viruses, including coronavirus, Lassa, Ebola, and Nipah.

Another challenge is the lack of experience in antiviral development. Most antivirals developed in the past 40 years have been used against HIV and viral hepatitis, which cause diseases slowly. In contrast, viruses like Ebola progress rapidly, requiring fast-acting antivirals. The current models to predict antiviral efficacy are limited, leading to variable results in clinical trials. For example, four antivirals against Ebola showed high success rates in animal studies but modest efficacy in clinical trials.

To improve antiviral therapy, it is crucial to not only optimize antivirals but also gain a deeper understanding of the pathophysiology of these viruses. The existence of zoonotic viruses that cause diseases in various ways offers an ideal test bed for antiviral development. This pandemic should serve as a wake-up call for increased resources to be allocated to these viruses. We must view them as common enemies, not exotic threats.

Conclusion

Preventing the next epidemic requires a comprehensive strategy that includes the development and deployment of effective vaccines and antivirals. By focusing on vaccines like mRNA vaccines and antivirals with broad-spectrum activity, we can significantly reduce the impact of future pandemics. The fight against viruses is an ongoing battle, and only through continuous research and innovation can we hope to achieve lasting success.