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HEPATITIS C VACCINATIONS

Who Fact Sheet No. 164 Hepatitis, article excerpt on Prevention:

Prevention

There is no vaccine against HCV. Research is in progress but the high mutability of the HCV genome complicates vaccine development. Lack of knowledge of any protective immune response following HCV infection also impedes vaccine research. It is not known whether the immune system is able to eliminate the virus. Some studies, however, have shown the presence of virus–neutralizing antibodies in patients with HCV infection.

In the absence of a vaccine, all precautions to prevent infection must be taken including:

  • Screening and testing of blood and organ donors;

  • Virus inactivation of plasma derived products;

  • Implementation and maintenance of infection control practices in health care settings, including appropriate sterilization of medical and dental equipment;

  • Promotion of behavior change among the general public and health care workers to reduce overuse of injections and to use safe injection practices; and

  • Risk reduction counseling for persons with high-risk drug and sexual practices.

JOHN HOPKINS MEDIA - April 26, 2002

MEDIA CONTACT: Trent Stockton
PHONE: 410-955-8665
E-MAIL: tstockt1@jhmi.edu

Need, Potential for Hepatitis C Vaccine Highlighted by Hopkins Study  

"Our findings suggest that humans can acquire immunity that protects against the disease caused by hepatitis C virus."

Humans may be able to develop immunity to hepatitis C virus, according to a study by Hopkins researchers published in the April 26 issue of The Lancet, findings that add to a growing body of evidence that immunity to the virus can be acquired. The findings are important because no vaccines exist for preventing hepatitis C in humans although preliminary vaccine research in primates appears promising.

Other studies in chimpanzees demonstrate that although animals who were previously infected or vaccinated could be infected with hepatitis C virus, those infections were less likely to persist compared to animals infected for the first time, according to David L. Thomas, associate professor of medicine at Hopkins and lead author of the study.

"We found the same in humans, suggesting that humans can acquire immunity that protects against hepatitis C virus persistence," says Thomas. "If this is indeed the case, it suggests that vaccines can be used to protect us from the long-term complications of hepatitis C infection, like liver cirrhosis and liver cancer."

In their study of injecting drug users from Baltimore, Md., Thomas, co-author Shruti Mehta, M.P.H., and colleagues identified 164 people whose blood tests revealed no evidence of previous hepatitis C infection, and 98 people who had been infected in the past but were not currently infected with the virus. They compared the incidence and persistence of infection in these two groups over four consecutive six-month periods.

People previously infected were half as likely to develop new infections compared to those who had not been previously infected (12% compared to 21%, respectively). Among HIV-1-negative people, those previously infected were 12 times less likely to develop persistent infection than people infected for the first time .

"The medical consequences of hepatitis C virus are tremendous," says Thomas. "Our findings indicate that vaccines should be developed to reduce the burden of liver disease associated with hepatitis C infection."
Close to 4 million people in the United States and 170 million people worldwide have been infected with the hepatitis C virus. Eighty-five percent of those infected develop persistent infection and are at risk of serious complications such as liver cirrhosis and liver cancer, according to Thomas.

Other authors of the study are Stephanie Strathdee, Ph.D., Andrea Cox, M.D., Xiao-Hong Wang, M.D., Qing Mao, M.D., and Stuart Ray, M.D., all from Johns Hopkins; Donald Hoover, Ph.D., of Rutgers University, and David Vlahov, Ph.D., of the New York Academy of Medicine. The study was funded by the National Institute on Drug Abuse and the National Institute of Allergy and Infectious Disease.

The Role of US Government Agencies in Vaccine Research and Development

Overview

A generation ago, some policymakers suggested that the time had come to "close the book" on infectious diseases. With the availability of a growing arsenal of antibiotics and vaccines, and the eradication or near-eradication in developed countries of diseases such as smallpox, polio and diphtheria, it was argued that biomedical research resources should be diverted from infectious diseases to other concerns.

Today, as we approach the 21st century, the folly of this position has become clear. One needs only to talk to our older citizens to be reminded of this. My 87 year-old father, for instance, has in his lifetime experienced two global pandemics with extraordinary impact. As a young boy in New York he saw many relatives and acquaintances succumb to influenza during the great flu pandemic of 1918, which claimed at least 20 million lives worldwide. As a retiree, he has witnessed the emergence of the AIDS pandemic, which, like the flu pandemic of 1918, has afflicted people on every continent, often in the prime of their lives.

Clearly, we remain vulnerable to infectious diseases, old and new. Infectious diseases are the world's leading cause of mortality, and the third leading cause of death in the United States. Of approximately 52 million deaths worldwide from all causes in 1996, more than 17 million were due to infectious diseases, including approximately 9 million among children. In 1996 alone, an estimated 3 million deaths worldwide were attributed to tuberculosis, 2.5 million to diarrheal diseases, 1.5 to 3.0 million to malaria (including one million children under age five), and 1.2 million to the sequelae of chronic hepatitis B virus infection. In addition to their human toll, the financial burdens of infectious diseases are enormous. In the United States alone, costs associated with infectious diseases have been estimated to exceed $120 billion annually.

Many serious infections are becoming increasingly resistant to first-line, and in some cases second- and third-line antibiotics, making treatment difficult and in some cases impossible. For example, among the more than 90 countries where Plasmodium falciparum malaria is endemic, only those in Central America and Egypt have not recorded cases of chloroquine-resistant malaria. Resistance to fansidar is common in many parts of the world, and in Thailand and certain regions of neighboring countries more than half of P. falciparum infections do not respond to mefloquine. Drug-resistant tuberculosis has now been found in virtually every country surveyed. Recent data show that more than 10 percent of people with tuberculosis are infected with strains of Mycobacterium tuberculosis resistant to at least one of the four first-line anti-TB drugs.

In the United States, more than one-third of Staphylococcus aureus isolates are now resistant to methicillin, leaving vancomycin as the only available drug that reliably eradicates them. Ominously, vancomycin-resistant S. aureus isolates were identified for the first time in 1997.

Superimposed on the many serious endemic infectious diseases that threaten human health, and on the problem of drug-resistance, are more than 40 diseases and syndromes newly recognized since the mid-1970s. Perhaps the most notable of these agents is the human immunodeficiency virus (HIV), the cause of the acquired immunodeficiency syndrome (AIDS). In 1996, AIDS-associated illnesses caused the deaths of approximately 1.5 million people worldwide, including nearly 39,000 people in the United States. Another emerging pathogen of great concern is the hepatitis C virus (HCV), a leading cause of cirrhosis, liver cancer, and a major reason for liver transplants. Worldwide, more than 170 million people are chronically infected with HCV, including 4 million individuals in the United States. Annual HCV-related deaths number approximately 8,000 to 10,000 people in this country, a figure projected to reach 24,000 deaths/year by 2017 if effective therapies are not found.

Innogenetics Research for a Therapeutic hepatitis C vaccine

About Hepatitis C

Chronic hepatitis C infection is a potentially life-threatening liver disease caused by the hepatitis C virus (HCV). According to the World Health Organization, over 170 million people worldwide are chronically infected, later giving rise in over 20% of those patients to serious liver disease such as liver cirrhosis and liver cancer. Unfortunately, current interferon-alpha based treatments are only effective in about 40% of patients infected with HCV genotype 1, which is the most common genotype in the Western world.

Treatment of chronic hepatitis C is characterized by a dual objective: preventing progression of liver disease by reducing the amount of virus in the body to low levels, and modifying the process of liver inflammation. Interestingly, the hepatitis C virus itself is not believed to be directly damaging to liver cells. This is shown by the fact that many chronic HCV carriers remain healthy and never develop op liver complications, some show milder liver degeneration, while others develop op life-threatening complications.

About the research and development program

In the early 1990’s, Innogenetics entered the uncharted territory of hepatitis C therapeutics by starting its research into a vaccine. On the basis of its extensive experience in hepatitis C research, scientists at Innogenetics observed that those patients with chronic hepatitis C who responded well to interferon therapy, also had higher quantities of anti-HCV E1 antibodies in the blood. The E1 protein is an important component of the hepatitis virus since it is part of the virus’ envelope.

After promising preclinical results in chimpanzees, and a successful Phase I clinical trial in healthy adults, Innogenetics began a Phase IIa clinical study to explore the safety and immune response of the E1 candidate therapeutic vaccine in patients with chronic hepatitis C infection. Most of the study patients had failed interferon-based therapy in the past. All patients were infected with HCV genotype 1, which generally responds less well to current treatment options. The patients received four injections at four-week intervals followed by a booster three months later (week 24). Follow-up visits are planned up to week 48.

This exploratory Phase IIa study was conducted at five centers in Belgium. A total of 26 patients were randomized to E1, while 9 patients were randomized to placebo. It should be emphasized that the number of placebo and E1-treated patients was deliberatly kept low for ethical and safety reasons, respectively. The results from such an initial Phase IIa trial is a means to not only gauge safety and immunogenicity, but also provide important data that can help fine-tune the candidate vaccine for further studies (by optimizing the dose, vaccine schedule, etc.).

An interim analysis was conducted at week 28 as per protocol. At week 28, the available data indicated that the candidate vaccine was generally well tolerated. No adverse reactions that would jeopardize the continuation of the clinical development program were identified at that stage.
In terms of immune response (immunogenicity), two parameters were measured: the serum levels of detectable anti-E1 antibodies (humoral immune response) and the proliferation of T lymphocytes to E1 challenge (cellular immune response). It should be noted that in patients chronically infected with HCV, antibodies to E1 are typically low, while a cellular response to E1 is most often not even detected. At week 28 of this phase IIa study, antibody levels and especially the T-cell proliferation indices increased significantly in the vast majority of the patients treated with E1.

No repeat liver biopsy evaluation was included in this first exploratory Phase IIa protocol. In the absence of such liver histology data, serum levels of alanine aminotransferase (ALT), reflecting liver damage, and HCV ribonucleic acid (RNA), indicating the presence of the virus in blood were monitored. At week 28 of the study, the patients treated with the candidate vaccine showed a significant decrease in ALT from baseline; a few patients also showed drops in HCV-RNA. No significant intergroup differences were observed for ALT and HCV-RNA at week 28, as the limited sample size of this exploratory study could not provide sufficient statistical power to identify medium size differences between treatment groups. This will be assessed in further trials where larger patient and placebo groups will be included. Future trials will also be able to monitor changes in liver histology, the gold standard for measuring the health of liver tissue.

The patient follow-up results of the Phase IIa study will be announced in the second quarter of 2002, together with the next steps in the development process of the E1 candidate therapeutic vaccine.

Clinical development plan:

Phase I: 2000
Phase IIa: 2001-2002
Announcement of next steps: 2nd quarter 2002
Expected market launch: 2006-2007

© 2003 California Hepatitis Resource Center