World Immunization Week: Taming Latent Viruses for Longer Lives

The World Health Organization created World Immunization Week to highlight global collective action and promote the use of vaccines that keep all of us protected against disease. This year, the theme is “Long Life for All: In pursuit of a long life well lived.”

The COVID-19 pandemic demonstrated the criticality of mRNA vaccines as a tool for quickly and effectively battling disease to improve lives around the world.And though several COVID-19 vaccines are now readily available, our work doesn’t stop there. Right now, more than 225 viruses affect people globally, yet only 25 of them have available vaccines. Moderna has an obligation to leverage our mRNA platform to investigate new vaccines that enable the “pursuit of a long life well lived” for people all over the world.

Understanding Latent Viruses

Viruses are a natural part of our day-to-day lives–even when they’re in our bodies. While the immune system gets rid of most viruses in just days to weeks, some viruses linger inside us for prolonged periods, hiding quietly without causing any symptoms. Such viruses are called “latent,” and include Epstein-Barr virus (EBV), Varicella-Zoster virus (VZV), HIV, Herpesviruses, and Cytomegalovirus (CMV). When they come out of hiding, or “reactivate,” latent viruses can cause transient (temporary) symptoms or persistent disease. For example, Herpesviruses are a large family of viruses that cause chicken pox, shingles, and more.

Latency is a survival strategy some viruses use to help them stay alive and spread (aka, self-propagate). Latent viruses have evolved to trick their host’s immune system from completely clearing away the virus, allowing it to reactivate periodically. During those periods of reactivation, an infected person sheds the virus through bodily fluids such as saliva, blood, and urine, allowing it to infect those in close contact with the host person.

Latent Viruses & Reactivation

Latent viruses may periodically reactivate as a normal part of viral lifecycle. This can occur when there is a specific trigger such as a different infection that distracts the immune system, and or when an external stimulus reaches the latent reservoir cells, ‘awakening’ the viral genome to start producing active viral particles rather than staying quiet.

In a healthy person, reactivation of a latent virus may not cause noticeable symptoms or disease—or it may lead to lifelong problems. The immune system’s memory (either from a previous infection or vaccination) quickly kicks-in to control viral replication before tissue damage can occur. In other cases, however, the consequences of reactivation can be severe. For instance, an initial encounter with VZV causes chicken pox; subsequent reactivation later in life can cause shingles.

Cytomegalovirus (CMV) is another example of a latent virus that remains in the body for life once a person is infected. In the US, more than half of people over the age of 40 have been infected with CMV, the vast majority of whom have no symptoms. CMV infection in the womb, however, can cause serious long-term health problems. This is because CMV can interfere with normal fetal development, leading to deafness, seizures, and developmental delays. CMV occurring from birth (congenital) is the leading infectious cause of birth defects in the US, yet 91% of women have never heard of it.

Another example of a latent virus is Epstein-Barr virus (EBV), which can be found in more than 90% of people worldwide. EBV was previously believed to be a harmless (benign) virus that remained in its host for the person’s entire lifespan once they became infected. Though EBV typically causes no symptoms, occasionally the virus causes infectious mononucleosis (mono) before going dormant, resulting in fever, aches, and extreme fatigue. Recent studies now suggest a link between EBV, multiple sclerosis (MS), and some types of cancer.

Protecting the Immunocompromised

For people with compromised immune systems, such as the elderly, those with organ transplants, and people with HIV infection, the consequences of latent virus reactivation can be even more dire. In these cases, the risk of severe disease, with increased morbidity and mortality from other viral infections (including other latent viruses), is much higher.

In people with compromised immune systems, both the primary infection and the reactivation of a latent virus can be debilitating as the weakened immune system struggles to control the infection.Complications of a latent virus infection can include painful short- and long-term disease (e.g., shingles and subsequent herpetic neuralgia), transplant rejection, and even end organ failure. Therefore, it is critically important to protect these populations against reactivation-associated disease.

How mRNA Vaccines Can Help

Our hope is that countless diseases caused by latent viruses can be prevented altogether by halting latent virus infection through the use of mRNA vaccines in the future. And establishing immunity could change the way viruses affect our lives, potentially making latent viruses less of a health risk and reduce the healthcare and hospitalization costs that result from latent viral infections.

This is why, more than 10 years after our founding, we’re dedicated to delivering on the promise of mRNA science to create a new generation of transformative medicines for patients.

At Moderna, we are committed to developing a portfolio of first-in-class vaccines against latent viruses for which there are still no approved vaccines, including EBV, CMV, and HIV. Our team is working to bring even more vaccines against latent viruses to the clinic. We believe that developing vaccines for these viruses can have a profound impact on quality of health for hundreds of millions of people around the world.

When it comes to the “pursuit of a long life well lived,” we’re just getting started.