Saturday, January 28, 2023

Is There A Vaccine For Hepatitis C Virus

How Are Hepatitis B And Hepatitis C Spread From Person To Person

Hepatitis C Virus

Like HIV, the hepatitis B and hepatitis C viruses spread:

  • From mother to child: Pregnant women can pass these infections to their infants. HIV-HCV coinfection increases the risk of passing on hepatitis C to the baby.
  • Sexually: Both viruses can also be transmitted sexually, but HBV is much more likely than HCV to be transmitted sexually. Sexual transmission of HCV is most likely to happen among gay and bisexual men who are living with HIV.

The Need For A Therapeutic Hcv Vaccine

Current gold-standard therapy for HCV infection is weekly subcutaneous injections of pegylated interferon combined with daily oral ribavirin for a period of 24 weeks for genotypes 2 and 3, and 48 weeks for genotypes 1 and 4. Therapy is fraught with significant side effects and leads to a sustained virological response in approximately 40-50% of patients with genotype 1 infection, 65-70% with genotype 3 and 80% of those with genotype 2. PEG-IFN and ribavirin treatment is also expensive and, at an average cost of approximately GB£7000 in the UK for a treatment course, is unaffordable in developing countries .

Two viral protease inhibitors are currently in Phase III clinical trials for HCV and more are in development. These drugs will need concomitant PEG-IFN/ribavirin therapy to avoid the rapid emergence of viral mutants and are currently only effective against genotype 1 infection. It is expected they will increase SVR rates following treatment to 70% . Because these drugs will be used together with PEG-IFN/ribavirin, the cost of treatment will rise further and additional side effects, in particular skin rashes, can be anticipated. The cost of a 3-month course of protease inhibitor in the UK is currently predicted to be GB£18,000-22,000 . Many other direct antiviral therapies are in development but these are unlikely to reach clinical application in the next few years.

When To Talk To Your Doctor

You may not realize that you’ve come in contact with hepatitis B or C because oftentimes there aren’t any symptoms. You should get tested if you’ve been in any situation that presents a risk of infection, like sharing needles. The CDC also recommends that all pregnant women get tested for hepatitis C.

Some people can be allergic to the hepatitis B vaccine, so you should also see your doctor if you experience any bad reactions after getting one of the doses.

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Prophylactic Vs Therapeutic Vaccines

Vaccine candidates with two different goals have been considered to control HCV epidemic: Prophylactic and therapeutic . The most widespread use of vaccination has always been to prevent a particular disease by building immunity in an individual prior to the first encounter with the pathogen, and thus becoming immune to a particular illness. On the other hand, therapeutic vaccination is meant to induce immune responses against a disease that is already in course in a given individual.

As we will later discuss in detail, the challenges for designing an effective prophylactic vaccine are vast . Many preventive vaccines against other viral pathogens are able to induce neutralizing antibodies that correlate with protection, which seems to be difficult to achieve for HCV. Nevertheless, even a low efficacy prophylactic vaccine might be useful to decrease the epidemic impact in high-risk populations by reducing the number of new infections.

How To Vaccinate Against Hcv Infection

Hepatitis C vaccine: How is it developing and is it possible?

The protective effect of several antibody and T-cell vaccines has been assessed in chimpanzees. There have been successes and some apparent failures of both approaches. Informative trends emerged when 13 published studies were analyzed collectively. This meta-analysis highlighted an impressive suppression and/or delay in peak acute-phase viremia in animals, regardless of whether they received an antibody or T-cell vaccine. Antibody vaccines may provide a better outcome as defined by prevention of persistence., In many of these studies apparent sterilizing immunity was observed in some chimpanzees, but so far only against closely matched viruses belonging to the same HCV genotype. Cross-genotype protection from persistence has been observed in animals with natural immunity to HCV because of prior infection, but whether vaccine-induced antibodies or T cells provide the same broad protection has not yet been tested. This is an important issue because there are at least 6 major HCV genotypes that show 25%30% divergence, and considerable genetic diversity also is observed within genotypes.

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Prophylactic Hcv Vaccine Candidates

Thus far, for all licensed vaccines against virus infections, NAbs are considered the immune correlate of in vivo protection . Therefore, the primary aim of an HCV prophylactic vaccine is to elicit cross-protective NAbs against various genotypes. In addition, it is important for an HCV vaccine candidate to elicit polyfunctional CD4+ and CD8+ T cells that correlate with HCV clearance following natural infections . Several prophylactic HCV vaccines are in clinical trials currently .

E1 and E2 are exposed on the surface of HCV virions, and therefore are the main targets of NAbs . E1 may be involved in the virus membrane fusion with endosomal membrane, while E2 directly binds to surface receptors SR-BI and CD81 . Most NAbs neutralize HCV infection by masking the receptor-binding domain on E2, especially the conserved CD81-binding sites . Naturally, the development of NAbs-based HCV vaccines has been focused on E1/E2. A leading HCV vaccine candidate comprising CHO cell-produced E1E2 heterodimers and the MF59C.1 adjuvant-elicited NAbs against HCVpp in mice and guinea pigs . In phase I clinical trial, this E1E2/MF59C.1 vaccine was shown to be safe, immunogenic and capable of inducing NAbs against a broad spectrum of HCV genotypes in volunteers .

In Case Of Contact With An Infected Persons Blood Sperm Or Vaginal Secretions

Consult a health-care professional or call Info-Santé 811 immediately if:

  • You have come into contact with the blood, sperm or vaginal secretions of a person who could be infected with the hepatitis B virus. You may have to receive preventive treatment that protects you from catching hepatitis B. This treatment is called post-exposure prophylaxis. It must be administered as soon as possible after contact

Consult a health-care professional if:

  • You have come into contact with the blood of someone who could be infected with the hepatitis C virus. You can get tested and receive appropriate care, as needed

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Treatments For Hepatitis C

Hepatitis C can be treated with medicines that stop the virus multiplying inside the body. These usually need to be taken for several weeks.

Until recently, most people would have taken 2 main medicines called pegylated interferon and ribavirin .

Tablet-only treatments are now available.

These new hepatitis C medicines have been found to make treatment more effective, are easier to tolerate, and have shorter treatment courses.

They include simeprevir, sofosbuvir and daclatasvir.

Using the latest medications, more than 90% of people with hepatitis C may be cured.

But it’s important to be aware that you will not be immune to the infection and should take steps to reduce your risk of becoming infected again.

How Is Hepatitis C Infection Prevented

Viral Hepatitis: Hepatitis A, Hepatitis B, Hepatitis C, HBsAg HBeAg Vaccine HCV HBV HBsAb

Unfortunately, there is no vaccine to prevent hepatitis C. To reduce your risk of getting hepatitis C:

  • Injection drug use is the most common way people get hepatitis C. Avoid injecting drugs to reduce your risk. If you do inject drugs, use sterile injection equipment. Avoid reusing or sharing.
  • Avoid sharing personal care items that might have blood on them
  • If you are a health care or public safety worker, follow universal blood/body fluid precautions and safely handle needles and other sharps
  • Consider the risks if you are thinking about tattooing, body piercing, or acupuncture are the instruments properly sterilized?
  • If youre having sex with more than one partner, use latex condoms correctly and every time to prevent the spread of sexually transmitted diseases, including hepatitis C.

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The Hepatitis B Vaccine

The first version of the hepatitis B vaccine was approved by the Food and Drug Administration in 1981. Since the early 1990s, the World Health Organization has recommended that all countries add the vaccine to their public immunization plans.

Several types of approved hepatitis B vaccines are available, including one suitable for people of all ages, from infants to adults. The Center for Disease Control recommends that everyone under age 19 get the vaccine, with infants receiving the first dose at birth. The agency also recommends that most adults get the vaccine, especially those who:

  • have sexual or common household contact with someone with hepatitis B
  • have more than one sexual partner
  • have experienced sexual abuse
  • are likely to be in contact with blood and bodily fluids at work
  • have other liver conditions, including hepatitis C
  • are being treated for sexually transmitted diseases, including HIV

The most common version of the vaccine requires three separate doses. There’s also a version that the FDA approved for adults that only requires two doses.

You can get the hepatitis B vaccine at the same time as other vaccines. You’ll never catch hepatitis B from the vaccine.

Combination vaccines also exist that protect against both hepatitis A and B. Once you’re vaccinated against hepatitis B, you should be immune for the rest of your life and won’t need a booster.

Hcv Cell Culture Models And In Vitro Neutralization Assay

Since HCV was first identified in 1989, the lack of an in vitro assay to evaluate NAbs has greatly hindered the development of HCV vaccine. In 2003, lentivirus/retrovirus-based HCV pseudo-particles systems were established , in which a packaging plasmid expressing HIV/MLV gag proteins and a plasmid expressing HCV envelope protein E1/E2 are cotransfected into human embryonic kidney 293 cells to produce lenti- or retro-viruses pseudotyped with the HCV envelope proteins. HCVpp mimics at least in part the entry process of authentic HCV virions, and has been used as a surrogate infection model to study HCV-specific NAbs. However, because HCVpp is produced in non-hepatocytes and generally not associated with lipoproteins, this system does not fully recapitulate the natural HCV infection.

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Getting Tested For Hepatitis C

Seek medical advice if you have persistent symptoms of hepatitis C or there’s a risk you’re infected, even if you do not have any symptoms.

A blood test can be carried out to see if you have the infection.

GPs, sexual health clinics, genitourinary medicine clinics or drug treatment services all offer testing for hepatitis C.

Early diagnosis and treatment can help prevent or limit any damage to your liver, as well as help ensure the infection is not passed on to other people.

How Are Hepatitis B And C Transmitted

Hepatitis C vaccine: Is it possible?

A key difference between hepatitis B and C is the way they are transmitted. Hepatitis B is typically transmitted through the exchange of bodily fluids like blood and semen, while Hepatitis C can only be transmitted through blood-to-blood contact.

This means that needle sharing is a big problem for the spread of both of these viruses, especially since most people are symptomless and dont know that they’re infected.

Hepatitis C is much more limited in how it can be spread. By contrast, hepatitis B can be spread several ways, including:

  • Birth: can be transmitted to a newborn during childbirth.
  • Sex: can be transmitted to or contracted from a partner through intercourse.
  • Sharing Items of Personal Hygiene: can be transmitted to or contracted from anyone through the use of items like razors and toothbrushes.

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Hepatitis C Vaccine Expected In Five Years

A protective vaccine against infection with hepatitis C could be in use within 5 years, says Professor Sir Michael Houghton, who co-won the Nobel Prize for Medicine and Physiology and discovered the hepatitis C virus in 1989.

Currently, there is not a U.S. FDA Approved vaccine to prevent HCV.

“While the advent of directly acting antivirals to cure hepatitis C has given us a huge weapon to turn the tide on this pandemic, there is no doubt that a vaccine is required to help the world reach its ambitious target of reducing new hepatitis C infections by 90% and mortality rates by 65% by 2030,” explained Sir Michael in a press statement issued on July 11, 2021.

Sir Michael and colleagues at the Li Ka Shing Applied Virology Institute are currently developing an adjuvanted recombinant vaccine, which is expected to induce the production of antibodies to multiple cross-neutralizing epitopes, making it harder for the virus to escape the humoral immune response.

This means many different antibodies are likely to be produced by this vaccine to prevent HCV infection, making it very hard for the virus to evade them by mutation and protecting the vaccine recipient from hepatitis C infection.

Sir Michael anticipates phase 1 trials in 2022 using different adjuvants followed by phase 2 human efficacy trials from 2023-2026, either in an at-risk population such as people who inject drugs or via human vaccine challenge trials.

Types Of Hepatitis C Infection

There are six major identified hepatitis C virus genotypes, that is, specific genetic sequencing of the virus. In the United States, genotypes 1, 2 and 3 are most common, with genotype 1 accounting for the majority of cases.

Your child’s genotype is important because certain genotypes respond better to treatment than others and the treatment regimen is different depending on the genotype. Your child’s doctor will test to see which genotype your child has before starting therapy for your child’s infection.

In addition to the genotypes of hepatitis C, there are two common forms of hepatitis C infection: acute and chronic.

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The Need For A Prophylactic Hcv Vaccine

The need for a prophylactic HCV vaccine may be debated, since a change in social or cultural practices, such as the prevention of IVDU and the efficient screening of blood products and medical instruments worldwide would abort most new HCV infections. In practice, however, eradication through cultural change may be unachievable since the source of HCV infection is unclear in up to 20% of infected people, the prevention of IVDU has, to date, not been possible, and HCV is particularly prevalent in poorer countries where there is limited capacity for the financial investment required to reduce transmission during medical procedures.

Immunizing Agents Available For Use In Canada

Ellie Barnes: Hepatitis C vaccine

Hepatitis A-containing vaccines

  • AVAXIM® and AVAXIM®-Pediatric , Sanofi Pasteur SA , Sanofi Pasteur Ltd.
  • HAVRIX®1440 and HAVRIX®720 Junior , GlaxoSmithKline Inc.
  • TWINRIX® and TWINRIX®Junior , GlaxoSmithKline Inc. Refer to Hepatitis B Vaccine in Part 4 for additional information about HAHB vaccine.
  • VAQTA® , Merck Canada Inc.
  • ViVAXIM® , Sanofi Pasteur Ltd.

Human immunoglobulin

  • GamaSTAN® , Grifols Therapeutics LLC.

Standard human immunoglobulin is a sterile, concentrated solution for intramuscular injection containing 15% to 18% immunoglobulin. It is obtained from pooled human plasma from screened donors and contains mainly IgG with small amounts of IgA and IgM. For complete prescribing information, consult the product leaflet or information contained within the product monograph available through Health Canada’s Drug product database.

Refer to Contents in Immunizing Agents Available for Use in Canada in Part 1 for lists of vaccines and passive immunizing agents available for use in Canada and their contents.

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Will There Be A Vaccine To Protect Against The Hepatitis C Virus

The discovery of the hepatitis C virus more than 20 years ago offered the promise of a vaccine to prevent life-long persistent infection and associated progressive liver diseases. To date, only a few candidate vaccines have been tested in human beings for safety and immunogenicity. None have yet been assessed for prevention of HCV infection or persistence. In the event that current vaccine candidates do not advance to efficacy trials, or fail to provide protection against HCV, the pipeline of alternatives appears to be very small. With a sharp reduction in new HCV infections because of effective screening of the blood supply, and the possibility that acute and chronic infections will be curable because of improving therapy, it is reasonable to ask if the considerable effort to develop a preventive HCV vaccine still is needed. The answer is almost certainly affirmative. Vaccines that protect against hepatitis A and B virus infections were first targeted to health care workers. The value of adding a vaccine to prevent accidental HCV infection in the workplace is clear.

Lack Of Economic Incentive

Despite the fact that vaccines are great tools to prevent diseases, usually they are not as profitable as are drugs and other health services, and therefore investing in vaccine development is less appealing for the pharmaceutical industry. Additionally, the development of vaccines with two different aims would probably be expensive, and including prime/boost vaccination strategies may result impractical. On another front, most newly infected individuals are PWID which mainly belong to populations with limited financial resources. This represents another discouraging aspect for companies interested in vaccine development.

From an economic perspective, though, there is well-reported evidence that vaccines are, in the long run, the most cost-effective public health measure after access to clean water. A vaccine to fight HCV will, most likely, not be an exception.

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Antiviral Host Immunity: Relevance To Vaccine Development

Following acute infection with HCV, approximately 20% of people will spontaneously clear the infection . This is in stark contrast to HIV where infection inevitably persists. The distinct clinical outcomes that follow acute HCV infection allow comparative analysis of antiviral immunity between these clinical groups – this has been the major focus of many research groups over the last decade. Although the exact mechanisms behind successful viral clearance are still not yet fully elucidated, it appears that multiple components of the immune system, both innate and adaptive, play a crucial role in this process . A key observation is that strong, broad adaptive immune responses are detected during acute infection and these persist in those who resolve infection – whereas persistent infection is associated with a weak, frequently undetectable HCV-specific T-cell response.

Viral-host immune interactions during acute and chronic HCV infection

HCV: Hepatitis C virus TCR: T-cell receptor.

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