Study Suggests Possibility Of Universally Effective AIDS Vaccine

October 30, 1997

A study by a research team based at the Massachusetts General Hospital (MGH) suggests that it may be possible to develop an AIDS vaccine that will be effective against the different versions of the virus found around the world. As reported in the November issue of the Journal of Virology, the researchers found that the immune system's killer cells, called cytotoxic T-lymphocytes (CTLs), are capable of recognizing different strains, or clades, of the human immunodeficiency virus (HIV). In the past it has been feared that the prevalence of different HIV strains in different parts of the world would require developing different vaccines targeted to each strain.

CTLs have become the focus of HIV vaccine research in recent years, as earlier vaccine strategies based on the activity of antibodies have not proven successful. The immune system teaches these killer cells to target a specific type of virus, bacteria or other foreign material. Cells targeted to a specific virus seek out and destroy virally infected cells by recognizing peptides -- small fragments of the proteins that make up that virus -- that are displayed on cell surfaces.

CTLs are not infected by HIV and usually mount a defense against the virus soon after the initial infection. In most patients, however, the levels of CTLs eventually decrease, allowing HIV levels to rise and AIDS symptoms to develop.

Recent research has produced evidence that CTL activity is likely to be be a key immune response against HIV. High CTL levels have been seen in long-term nonprogressors -- individuals who remain healthy despite being infected for many years -- and CTLs that target the virus have been found in people who remain uninfected despite many exposures to HIV. In addition, CTLs seem to play an important role in the immune response against other viral disease, like cytomegalovirus and Epstein-Barr virus.

"There really is a growing consensus in the field that generating a strong, virus-specific CTL response will be important in developing any successful vaccine against HIV," says Bruce Walker, MD, director of the Partners AIDS Research Center based at the MGH and senior author of the report. "Since those parts of world most affected by this disease do not have the resouces to take full advantage of current therapies, a vaccine is the only way we're going to be able to eliminate AIDS globally."

Most HIV-infected individuals in the United States and Europe are infected with clade B, while several other clades -- the most common are A, C, D and E -- predominate in Africa and Asia. The researchers tested CTLs taken from individuals infected with clade B HIV and tested whether they would recognize viral peptides from all of the major clades. All of the tested CTLs recognized peptides from at least one non-B clade virus, and most reacted against peptides from all clades tested. The team also tested CTLs from 14 infected individuals from Senegal, 10 of whom were infected with clade A virus, three with clade G and one with clade C. CTLs from all 14 individuals reacted against proteins from clade B viruses.

"We were very surprised to see this striking amount of CTL cross-reactivity," says Walker. "But this result is supported by previous observations that people infected with one strain seem be protected against other strains of HIV."

Walker notes that CTL-based vaccines are just beginning to be tested in human volunteers, and many questions remain to be answered. For instance, it is far from certain whether CTL activity alone would be sufficient to protect against either HIV infection or progression to AIDS. Future studies are needed to define exactly which immune system responses will be most important for protection against HIV.

Walker's coauthors include Huyen Cao, MD, first author, and Spyros Kalams, MD, from the MGH; Phyllis Kanki, DVM, Jean-Louis Sankale, MD, and Abdoulaye Dieng-Sarr, of the Department of Cancer Biology at Harvard School of Public Health; Gail Mazzara, PhD, of Therion Biologic Corporation in Cambridge; Bette Korber, PhD, of the Los Alamos National Laboratory in New Mexico; and Souleymane Mboup, MD, of University Cheikh Anto Diop in Dakar, Senegal. The research was supported by grants from the National Institutes of Health.

Massachusetts General Hospital

Related Immune System Articles from Brightsurf:

How the immune system remembers viruses
For a person to acquire immunity to a disease, T cells must develop into memory cells after contact with the pathogen.

How does the immune system develop in the first days of life?
Researchers highlight the anti-inflammatory response taking place after birth and designed to shield the newborn from infection.

Memory training for the immune system
The immune system will memorize the pathogen after an infection and can therefore react promptly after reinfection with the same pathogen.

Immune system may have another job -- combatting depression
An inflammatory autoimmune response within the central nervous system similar to one linked to neurodegenerative diseases such as multiple sclerosis (MS) has also been found in the spinal fluid of healthy people, according to a new Yale-led study comparing immune system cells in the spinal fluid of MS patients and healthy subjects.

COVID-19: Immune system derails
Contrary to what has been generally assumed so far, a severe course of COVID-19 does not solely result in a strong immune reaction - rather, the immune response is caught in a continuous loop of activation and inhibition.

Immune cell steroids help tumours suppress the immune system, offering new drug targets
Tumours found to evade the immune system by telling immune cells to produce immunosuppressive steroids.

Immune system -- Knocked off balance
Instead of protecting us, the immune system can sometimes go awry, as in the case of autoimmune diseases and allergies.

Too much salt weakens the immune system
A high-salt diet is not only bad for one's blood pressure, but also for the immune system.

Parkinson's and the immune system
Mutations in the Parkin gene are a common cause of hereditary forms of Parkinson's disease.

How an immune system regulator shifts the balance of immune cells
Researchers have provided new insight on the role of cyclic AMP (cAMP) in regulating the immune response.

Read More: Immune System News and Immune System Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.