Combination HIV vaccine induces diverse immune response

July 13, 1999

Preliminary analysis of data from a clinical trial testing two candidate HIV vaccines given together shows that the combination is safe and can stimulate diverse immune responses against HIV. The findings will be discussed by the study's principal investigator, Robert Belshe, M.D., of Saint Louis University, on Tuesday morning, July 13, at the International Society for Sexually Transmitted Diseases Research meeting in Denver.

This is the second Phase 2 HIV vaccine trial, and the largest to date, sponsored by the National Institute of Allergy and Infectious Diseases (NIAID). The trial, known as AVEG 202/HIVNET 014, is being carried out at 14 sites nationwide by two NIAID-sponsored networks, the AIDS Vaccine Evaluation Group (AVEG) and the HIV Prevention Trials Network (HIVNET). Dr. Belshe heads the Saint Louis University AVEG site.

Earlier studies in volunteers at low risk of HIV infection showed this combined vaccine approach held promise for activating both components of the immune system. One vaccine, ALVAC-HIV vCP205, stimulates cellular immunity, resulting in cytotoxic T cells (CTLs) that can kill HIV-infected cells. The other vaccine, SF-2 rgp120, stimulates production of HIV neutralizing antibodies, which can stop HIV from infecting cells. The vaccines contain only selected HIV genes or proteins, and not the whole virus, so an individual cannot become infected from receiving the vaccines.

The current trial, which opened in May 1997, enrolled 435 healthy men and women not infected with HIV. Because the primary goal of this study is to assess the immune response and safety of the vaccine combination in individuals at increased risk of becoming infected with HIV, more than 80 percent of the participants had recent histories of injection drug use or high-risk sexual behavior. All participants received extensive and repeated counseling on reducing high-risk behaviors.

Each participant was randomly assigned to one of three study groups. The first group received both vaccines; the second group received vCP205 and a placebo, or dummy vaccine; and the third group received two placebos. Volunteers received four doses spread out over six months; each time, they got one shot in each arm. By July 1998, all immunizations were completed. The participants will be followed for four years.

Dr. Belshe will report that the vaccines appear safe. Adverse side effects associated with either vaccine were generally mild.

The vaccines have induced anti-HIV immune responses in the majority of the volunteers. More than half of those individuals receiving vCP205 alone, and more than 90 percent of those receiving the vaccine combination, have developed antibodies that can inhibit HIV in a laboratory assay. So far, about one-third of the volunteers receiving either vCP205 alone or the combination vaccine have developed anti-HIV CTL responses. While the results are encouraging and support further evaluation of this vaccine strategy, the study was not designed to determine whether the vaccine combination can protect against HIV infection or AIDS.

Because vaccinated individuals may at times appear positive on a standard HIV antibody test, even though they are not infected, the research team was concerned that participation might put volunteers at risk of discrimination and other negative consequences. True infection, however, can be distinguished from vaccine-induced antibody responses by several tests. Encouragingly, the proportion of volunteers who reported that their participation resulted in a negative event with a major life impact was quite low.

Also reassuring was the fact that overall, participants reported a decrease in risky behaviors after one year in the study. These findings reflected the sustained efforts of the study team to counsel volunteers to practice safe sex and avoid high-risk behaviors.

During the course of the trial, 11 volunteers became infected with HIV as a result of high-risk behaviors: six in the placebo group, three in the group receiving vCP205 alone, and two in the group receiving the vaccine combination. Six of the 11 had received the full four-dose course of vaccine or placebo before becoming infected: three in the placebo group, two in the group receiving vCP205 alone, and one in the group receiving the vaccine combination. However, the trial is neither large enough nor conducted over a long enough period of time to determine vaccine efficacy, says Dr. Belshe.

vCP205, made by Pasteur Merieux Connaught (Lyon, France) with support from the French ANRS (Agence National de Recherches sur le SIDA), consists of a weakened canarypox virus that has been genetically altered to contain a few selected HIV genes. The canarypox virus cannot grow or cause disease in humans. SF-2 rgp120, made by Chiron (Emeryville, CA), is a genetically engineered copy of the HIV surface protein, gp120. SF-2 is a laboratory-adapted HIV strain.

Additional NIAID-sponsored studies are gathering more data on this vaccination strategy before a large-scale efficacy trial is considered. For example, two newer canarypox HIV vaccines are undergoing a head-to-head evaluation. The current study adds compelling new evidence that large-scale efficacy trials using these or similar vaccines are feasible in communities at risk. At this time, the data needed to consider moving into the next phase of testing is expected to be available by late 2000.
-end-
For information about AIDS vaccine clinical trials, call the AIDS Clinical Trials Information Service (1-800-TRIALS-A) or visit their Web site at www.actis.org.

NIAID is a component of the National Institutes of Health (NIH). NIAID conducts and supports research to prevent, diagnose and treat illnesses such as HIV disease and other sexually transmitted diseases, tuberculosis, malaria, asthma and allergies. NIH is an agency of the U.S. Department of Health and Human Services.

Press releases, fact sheets and other materials are available on the NIAID Web site at www.niaid.nih.gov.



NIH/National Institute of Allergy and Infectious Diseases

Related HIV Articles from Brightsurf:

BEAT-HIV Delaney collaboratory issues recommendations measuring persistent HIV reservoirs
Spearheaded by Wistar scientists, top worldwide HIV researchers from the BEAT-HIV Martin Delaney Collaboratory to Cure HIV-1 Infection by Combination Immunotherapy (BEAT-HIV Collaboratory) compiled the first comprehensive set of recommendations on how to best measure the size of persistent HIV reservoirs during cure-directed clinical studies.

The Lancet HIV: Study suggests a second patient has been cured of HIV
A study of the second HIV patient to undergo successful stem cell transplantation from donors with a HIV-resistant gene, finds that there was no active viral infection in the patient's blood 30 months after they stopped anti-retroviral therapy, according to a case report published in The Lancet HIV journal and presented at CROI (Conference on Retroviruses and Opportunistic Infections).

Children with HIV score below HIV-negative peers in cognitive, motor function tests
Children who acquired HIV in utero or during birth or breastfeeding did not perform as well as their peers who do not have HIV on tests measuring cognitive ability, motor function and attention, according to a report published online today in Clinical Infectious Diseases.

Efforts to end the HIV epidemic must not ignore people already living with HIV
Efforts to prevent new HIV transmissions in the US must be accompanied by addressing HIV-associated comorbidities to improve the health of people already living with HIV, NIH experts assert in the third of a series of JAMA commentaries.

The Lancet HIV: Severe anti-LGBT legislations associated with lower testing and awareness of HIV in African countries
This first systematic review to investigate HIV testing, treatment and viral suppression in men who have sex with men in Africa finds that among the most recent studies (conducted after 2011) only half of men have been tested for HIV in the past 12 months.

The Lancet HIV: Tenfold increase in number of adolescents on HIV treatment in South Africa since 2010, but many still untreated
A new study of more than 700,000 one to 19-year olds being treated for HIV infection suggests a ten-fold increase in the number of adolescents aged 15 to 19 receiving HIV treatment in South Africa, according to results published in The Lancet HIV journal.

Starting HIV treatment in ERs may be key to ending HIV spread worldwide
In a follow-up study conducted in South Africa, Johns Hopkins Medicine researchers say they have evidence that hospital emergency departments (EDs) worldwide may be key strategic settings for curbing the spread of HIV infections in hard-to-reach populations if the EDs jump-start treatment and case management as well as diagnosis of the disease.

NIH HIV experts prioritize research to achieve sustained ART-free HIV remission
Achieving sustained remission of HIV without life-long antiretroviral therapy (ART) is a top HIV research priority, according to a new commentary in JAMA by experts at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

The Lancet HIV: PrEP implementation is associated with a rapid decline in new HIV infections
Study from Australia is the first to evaluate a population-level roll-out of pre-exposure prophylaxis (PrEP) in men who have sex with men.

Researchers date 'hibernating' HIV strains, advancing BC's leadership in HIV cure research
Researchers have developed a novel way for dating 'hibernating' HIV strains, in an advancement for HIV cure research.

Read More: HIV News and HIV 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.