Vaccines in Clinical Trials

Date: April 1, 1996
Source: National Institutes of Health (NIH)
Author: National Institute of Allergy and Infectious Diseases (NIAID)

The National Institute of Allergy and Infectious Disease (NIAID) has supported and conducted clinical trials of vaccines for many years. Today's enhanced understanding of the immune system as well as extraordinary advances in molecular biology have fostered the accelerated development of many new and improved experimental vaccines. Designed to protect against a wide range of diseases from the flu to AIDS, these new vaccines are now being evaluated in clinical trials. Several of these vaccine trials are described below.

Genital Herpes Vaccine

Genital herpes causes both physical and physiological discomfort, and many infected people experience painful recurrences of genital blisters throughout their lives. Even when symptoms are not apparent, the herpes simplex virus, which causes genital herpes, can be transmitted to sexual partners. In addition, each year about 1,500 babies contract neonatal herpes infection from their infected mothers during labor or delivery, and about half of these infected babies die or suffer serious neurologic damage.

NIAID researchers and scientists supported by NIAID recently completed preliminary testing of the first genetically engineered vaccine for genital herpes in a small number of infected and uninfected adults. The vaccine proved to be safe and prompted an immune response that matched what occurs during a natural genital herpes infection. In volunteers who have genital herpes, the vaccine reduced the number of herpes outbreaks compared to those given a placebo. An expanded trial in infected volunteers is continuing to further determine the vaccine's safety, its ability to stimulate the immune system, and its effectiveness in preventing recurrences of herpes lesions. The vaccine also is being tested in uninfected people to evaluate its ability to prevent infection with the virus that causes genital herpes.

Vaccines for Respiratory Tract Infections

Pneumococcal pneumonia is a life-threatening respiratory tract infection caused by the bacterium Streptococcus pneumoniae. The current vaccine, available since 1983, does not protect children younger than 2 years and has been shown to be not highly effective in some elderly population. NIAID-supported researchers and others have developed conjugate pneumococcal vaccines that link the outer coat of the pneumococcal bacterium with proteins. These conjugate vaccines are more effective than existing pneumococcal vaccines in stimulating the immune system in babies and older people. The new vaccines contain up to 11 of the most common S. Pneumoniae strains that cause bloodstream infections, meningitis, and middle ear infections. NIAID is supporting clinical trials in high-risk populations such as the elderly and infants.

Influenza is a respiratory disease that can be particularly serious in older people and very young children. Influenza viruses are notorious for their ability to change the proteins on their outer surfaces, causing new outbreaks and periodic epidemics throughout the world. Although influenza vaccines have been available for many years, they provide short-lived protection and must be produced each year to protect against the particular strains of influenza prevalent during a given year.

NIAID scientists have developed a vaccine using live, weakened virus. This vaccine may be more effective because the virus is adapted to growing at colder temperatures, which means that it can infect the cooler upper respiratory tract, stimulating immunity, but not cause the disease in the warmer lungs. NIAID conducted a 5-year trial, among thousands of volunteers, that showed this vaccine to be as effective as the currently available inactivated vaccine. Further studies are under way in NIAID's Vaccine Treatment and Evaluation Units to examine the vaccine's safety and ability to stimulate an immune response in children when delivered as a nasal spray. NIAID continues to work with researchers and pharmaceutical companies to evaluate alternative vaccine delivery approaches.

Cholera Vaccine

Cholera is both a common and extremely deadly disease in many parts of the world. During 1991, it spread to South America, affecting more than a million people in the first epidemic there since the turn of the century. By causing unremitting diarrhea, which results in dehydration, the toxin produced by cholera bacteria can kill a person in less than 24 hours. Although antibiotics and oral rehydration therapy can effectively treat persons with cholera, the disease still kills many of those who do not have a quick access to medical care. This was most recently demonstrated among the refugees in Rwanda, when cholera swept through refugee camps.

NIAID-supported investigators have developed an experimental oral cholera vaccine using live cholera bacteria in which the toxin genes have been modified. This vaccine was well-tolerated, stimulated the immune system, and protected volunteers who received just a single dose. It has been tested, with technical assistance from NIAID, in adults and young children in the U.S., Chile, Indonesia and Peru and was shown to be safe and able to stimulate an immune response. A large trial involving more than 60,000 people is now under way in Indonesia to determine if the vaccine is effective in preventing cholera. This vaccine has been licensed in several European countries, and U.S. licensure will be sought by the manufacturer in the near future. Other experimental vaccines directed against a new strain of the cholera bacterium also have been developed with NIAID research support and are being evaluated in clinical trials in U.S. volunteers.

AIDS Vaccines

In 1987, NIAID began the first clinical trial of an experimental vaccine against HIV, the virus that causes AIDS. Since the first trial, about three dozen preventive HIV vaccine trials have been initiated worldwide. As of January 1996, nearly 1,800 men and women had participated in HIV vaccine trials conducted at six NIAID-supported AIDS Vaccine Evaluation Units. To date, all the vaccine candidates tested have been well tolerated, generally producing only mild side effects typical of most vaccines.

The challenges in HIV vaccine development are enormous. Researchers do not know what constitutes immune protection against HIV or whether a natural protective state can exist. Unlike other vaccines, an HIV vaccine may need to stimulate both cellular and mucosal immunity. Moreover, HIV continually evolves as a result of genetic mutation and recombination, so that a successful vaccine must generate immune responses that protect noninfected people from all the different HIV subtypes to which they may be exposed; Although the challenges are daunting, scientists remain optimistic that safe and effective HIV vaccines can be developed.

Impact of New Vaccines

As new vaccines emerge from the laboratory into clinical testing and finally into general use, many commonplace diseases will become as rare as polio and diphtheria are today in the United States. This has been demonstrated recently by the virtual elimination in just a few years of childhood meningitis caused by Hemophilus influenzae type b, which is now prevented by effective conjugate vaccines. A recently licensed vaccine to prevent hepatitis A, developed by NIAID scientists, is likely to have a major impact on the incidence of this disease in the future. By continuing to refine the technology used to create vaccines, new ones are likely to be developed that will be more available and more easily administered to people in other parts of the world as well.

Prepared by: Office of Communications National Institute of Allergy and Infectious Diseases National Institutes of Health Bethesda, Maryland 20892 Public Health Service U.S. Department of Health and Human Services April 1996