New Vaccines in the Pipeline 2020
Second Erie-area Hepatitis A Vaccine Clinic Set After First One Runs Out Of Vaccine
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Everything You Want To Know About Hepatitis C
Hepatitis C is a viral condition that leads to inflammation of the liver. Hepatitis C infections can be acute or chronic. A chronic infection can lead to serious complications, but appropriate treatment can usually cure the hepatitis virus.
Hepatitis C is an inflammation of the liver that develops after contracting the hepatitis C virus (HCV). HCV is bloodborne, which means you can only transmit or contract it through blood that carries it.
The World Health Organization (WHO) estimates around 58 million people globally are living with chronic hepatitis C.
In the United States, hepatitis C is among the most common types of hepatitis, along with hepatitis A and B. There are vaccines to prevent hepatitis A and B, but a vaccine to prevent hepatitis C doesn't yet exist.
Stages of hepatitis CHepatitis C can be either acute or chronic.
Doctors generally define acute hepatitis C as the first 6 months after infection. It is most often asymptomatic. Any symptoms you experience may appear within 2–12 weeks after exposure, and they could clear up on their own.
Chronic hepatitis C symptoms, on the other hand, can develop (and worsen) over months or even years. You might not notice any symptoms until they become severe.
Left untreated, hepatitis C can cause serious, even life threatening complications, including:
Symptoms may develop 2–12 weeks after exposure. The first 6 months after infection are considered acute.
Acute hepatitis C may cause:
If your body doesn't clear the virus, acute hepatitis C will become chronic. An estimated 55–85% of people who contract HCV will eventually develop chronic hepatitis C.
Chronic hepatitis C may cause:
These symptoms might affect you most of the time or improve for a while and then worsen.
With chronic hepatitis C, you could also notice some symptoms of liver scarring and liver disease, including:
Hepatitis C is a liver disease that occurs due to HCV infection. HCV transmits through blood-to-blood contact.
This can happen as a result of:
You have an increased risk of HCV infection if you:
It's important to consult with a doctor or other healthcare professional if you suspect that you've had exposure to HCV. You can contract HCV more than once.
Your healthcare professional will order blood tests to check for the virus, starting with an antibody test.
If you've ever had an HCV infection, your body will make hepatitis C antibodies part of its immune response. It may take 2–3 months after exposure for the test to detect antibodies.
If the antibody test is positive, a nucleic acid test for ribonucleic acid (RNA) can tell your healthcare professional whether the virus is currently active.
In the event of an active HCV infection, tests to measure the amount of virus in your blood (viral load) and determine which genotype you have will guide an effective treatment plan.
If blood test results suggest chronic hepatitis C or your healthcare professional believes you could have liver damage, they'll order a liver function test. This test checks your blood for signs of heightened enzymes in your liver.
A type of scan called ultrasound elastography can be used to assess liver damage.
A liver biopsy can also check for liver damage. A biopsy involves taking a small piece of tissue from your liver and testing it for cell abnormalities.
Oral medications called direct-acting antivirals (DAAs) work to remove HCV from your body and reduce the risk of liver damage.
Treatment often includes two or more DAAs taken in combination. Some treatments are available as pills containing two or more drugs.
Common brand names include:
A typical course of treatment lasts 12–24 weeks.
Is hepatitis C curable?
Treatment can cure hepatitis C 95% of the time. Healthcare professionals consider the condition cured when tests can't detect the virus in your blood 12 weeks after treatment ends.
HCV infection causes liver inflammation. Over time, this damage can cause permanent scarring, known as cirrhosis.
Cirrhosis interferes with blood flow and prevents your liver from functioning effectively. An estimated 15–30% of people with chronic hepatitis C develop cirrhosis within 20 years.
Untreated or unmanaged cirrhosis can lead to:
Advanced liver disease can also lead to:
It takes a long time for chronic hepatitis C to cause liver failure. Liver failure or end stage liver disease, happens slowly over months, often years. When your liver becomes unable to function properly, you'll need a transplant.
Experts have yet to develop an effective hepatitis C vaccine, though research continues.
Currently, the best way to reduce your risk of infection is to avoid using any items that may have come into contact with someone else's blood.
You can do this by:
If you think you could have hepatitis C, getting tested right away doesn't just help you get treatment. It can also help you avoid transmitting the virus to others.
You can contract HCV through blood-to-blood contact with someone who has the virus. While your body might clear an acute infection without treatment, hepatitis C often develops into a chronic condition.
Prompt diagnosis and treatment can help reduce the risk of long-term complications, including severe liver damage and liver failure.
Regular hepatitis C screenings can help with early detection. Consult with a healthcare professional to develop a screening schedule tailored to your individual level of risk.
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Patient Who Spontaneously Cleared Hepatitis C Could Inspire Vaccine
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By studying individuals who spontaneously clear hepatitis C infections, a team of researchers has identified viable vaccine targets for a disease that infects 70 million worldwide with case numbers increasing every year.
It turns out that a quarter of people who become infected with the hepatitis C virus clear the infection on their own without treatment, while the remaining three-quarters of people develop chronic infections that can last for years. The blood-borne disease – which causes liver cirrhosis, liver failure and liver cancer – is especially prevalent among people who inject drugs.
Direct-acting antivirals developed around a decade ago are 98% effective. But even so, the number of hepatitis C cases has increased year-over-year mainly because early infections are hard to detect, access to treatment is limited and reinfections occur even after treatment.
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Subscribe for FREE"That's why there is now a big interest in developing a hepatitis C vaccine," said Andrew Flyak, assistant professor of microbiology and immunology in the College of Veterinary Medicine and co-corresponding author of the study, "Convergent Evolution and Targeting of Diverse E2 Epitopes by Human Broadly Neutralizing Antibodies are Associated with HCV Clearance," which published March 21 in the journal Immunity. Justin Bailey, associate professor of medicine at Johns Hopkins University, is co-corresponding author.
"Our study gives us a glimpse into how certain individuals clear a highly variable infection, and we believe this information can inform a vaccine development," Flyak said.
The study was made possible due to the unique access that Bailey had to samples from people who injected drugs and were at risk of acquiring the virus. This allowed the researchers to track individuals who were hepatitis C negative when they enrolled in the program, and to see upon subsequent clinic visits whether that person acquired the virus. Bailey obtained samples from individuals who cleared the infection on their own and those who developed chronic infection.
Viruses that evolve very rapidly, such as SARS-CoV-2, influenza and hepatitis C, have extraordinary genetic diversity with multiple strains. Combating these types of infections requires special antibodies (blood proteins that recognize pathogens and neutralize them) called broadly neutralizing antibodies (bNAbs), which can neutralize diverse viral variants.
In previous studies, researchers isolated bNAbs from people who were chronically infected with hepatitis C virus. They found that their bNAbs were using a single antibody gene to encode a variable part of the antibody molecule.
"In order to make an antibody, immune systems use multiple sets of different antibody genes, but for whatever reason the immune systems in people with chronic hepatitis C infections used just one variable antibody gene, called VH1-69," Flyak said. Also, most of the bNAbs from these chronically infected donors targeted a specific region of the hepatitis C virus, namely the front layer of the so-called E2 protein. The immune system in chronically infected individuals has failed to clear the virus.
In the current study, the researchers isolated bNAbs from one person who spontaneously cleared three separate infections. This individual's bNAbs revealed important distinctions. First, these bNAbs were genetically diverse, meaning they are encoded by a variety of variable genes, and not just one segment of the VH1-69 gene. Second, bNAbs from this individual targeted three different regions of the virus' E2 protein, the front layer, as well as a back layer and a b-sandwich.
The data suggests that a hepatitis C virus vaccine should elicit bNAbs to all three regions of the E2 protein rather than just one region of the virus, Flyak said.
"If you have a response to multiple regions, you can have a synergistic effect, you get a response that is much stronger than the sum of its parts," he said.
BNAbs from the individual who cleared the infections also revealed evidence of what is called convergent evolution, where different bNAbs have the same mutations but come from different antibody variable genes. "You see the same mutations in two different broadly neutralizing antibodies – it means those mutations are important," Flyak said – and they increase the breadth of the antibody response to hepatitis C virus.
Members of Flyak's lab used X-ray crystallography to solve the crystal structures of bNAbs in complex with hepatitis C virus' E2 protein and show how bNAb's mutations interact with the E2 protein. "That information can be used to design better vaccine candidates," Flyak said.
In next steps, the team will collaborate with a larger international group to screen multiple vaccine candidates in animals and eventually identify which ones to bring into human clinical trials.
Reference: Ogega CO, Skinner NE, Schoenle MV, et al. Convergent evolution and targeting of diverse E2 epitopes by human broadly neutralizing antibodies are associated with HCV clearance. Immunity. 2024:S1074761324000979. Doi: 10.1016/j.Immuni.2024.03.001
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