World-changing mRNA vaccines

Avian influenza is a disease caused by infection with avian (bird) influenza (flu) Type A viruses, which spreads among wild aquatic birds worldwide and can infect domestic poultry and other bird and animal species.

Penn Medicine researchers, led by Scott Hensley, PhD, and Drew Weissman, MD, PhD, have developed an experimental mRNA vaccine against avian influenza virus H5N1, and it is highly effective in preventing severe illness and death in preclinical models. The vaccine could potentially help manage the H5N1 virus in birds and cattle and prevent human infections.

While COVID-19 is the most recognizable disease caused by a coronavirus, it is not the only one. Penn scientists are working on an mRNA vaccine that provides the immune system with information to combat any coronavirus, including those that cause:

• Severe acute respiratory syndrome (SARS)
• Middle East respiratory syndrome (MERS)
• Future coronavirus-induced diseases

Scientists at Penn Medicine and Children’s Hospital of Philadelphia have created the first mRNA vaccine for Clostridioides difficile (C.diff), a difficult-to-treat and highly contagious infection. In early clinical trials conducted with small animals, the vaccine showed strong results—it stopped both new and repeat infections, cleared existing bacteria, and worked even when the immune system was weaker.

Herpes simplex virus 2 (HSV-2) is the most common sexually transmitted disease. Penn researchers are creating an mRNA vaccine for HSV-2 that instructs the body to:

• Block the herpes virus from entering cells
• Make sure that the virus doesn't turn off the immune system's normal protective functions

Hepatitis C is a liver infection that can become chronic and life-threatening. Penn scientists are developing an mRNA vaccine that tells the body to create antibodies that neutralize the hepatitis C virus (HCV) and prevent infection.

Human immunodeficiency virus (HIV) attacks the body's immune system and, if not treated, can lead to acquired immunodeficiency syndrome (AIDS). Penn researchers are working on an mRNA HIV vaccine that teaches the body to recognize and stop thousands of HIV variants before they cause harm.

Influenza (flu) viruses change constantly, so researchers must develop a new flu vaccine each year. Most seasonal flu vaccines are only 10 to 60 percent effective because it’s difficult to keep up with the many circulating viruses.

Penn Medicine researchers have developed a mRNA-based vaccine against all 20 known subtypes of influenza virus. If clinical trials are successful, this universal flu vaccine will give people a baseline level of immune memory against diverse flu strains and could protect against future flu pandemics.

Leptospirosis is a bacterial disease that humans can get from contact with urine or other bodily fluids (except saliva) from infected animals. Penn researchers are working on an mRNA vaccine to combat this disease, which is most common in southeast Asia.

Malaria passes to humans through bites from infected mosquitoes and causes high fevers, shaking chills, flu-like symptoms and anemia. The disease can be fatal and is a major health problem in the tropics and subtropics.

The current malaria vaccine is only 40 percent effective and must be given annually. Penn researchers are developing mRNA vaccines that are more robust and long-lasting with the goal of preventing transmission and disease.

Norovirus is a contagious viral condition that causes severe diarrhea, nausea, vomiting and stomach pain. The virus is particularly dangerous for young children, the elderly and immunocompromised people.

Scientists have had difficulty creating a norovirus vaccine using traditional methods. Penn researchers are now using mRNA technology to develop an effective, rapid-response vaccine.

Tuberculosis (TB) disease is an infectious airborne condition that usually affects the lungs but can also settle in the brain, kidneys or spine. If not treated, TB can be fatal.

Not everyone infected with TB develops TB disease right away or at all. This is called a latent TB infection. Penn researchers are working on an mRNA vaccine that prevents a latent TB infection from turning into TB disease.

An inherited (runs in families) genetic defect in the cystic fibrosis transmembrane conductance regulator (CFTR) causes cystic fibrosis, a life-threatening condition. Penn researchers are considering ways to treat cystic fibrosis by:

• Delivering mRNA into the lungs where it will instruct cells to create healthy CFTR
• Altering the DNA to fix the defected CFTR protein

Sickle cell anemia is an inherited condition in which red blood cells are deformed and stiff, resulting in numerous complications. Most advanced treatments are not possible in rural Africa and India, home to most of the 200,000 people born each year with the disease.

Penn researchers are developing a single-injection therapy that sends mRNA to bone marrow stem cells. The mRNA instructs the cells to repair the genetic defect, thereby curing the disease. If successful, this therapy could translate to other congenital (present from birth) gene defects in blood and stem cells.