Vaccine Briefs

Lasker Awardees Announced

The winners of this year's Albert Lasker Medical Research Award were announced on September 17 in advance of the awards ceremony, which will take place on September 28 in New York City. This year's awardees include two scientists—Ralph Steinman and Tony Fauci—who have contributed substantially to the fields of HIV/AIDS and immunology.

Ralph Steinman of Rockefeller University was awarded the Lasker for Basic Medical Research for his seminal work on the discovery of dendritic cells (DCs), a principal subset of immune cells that control the body's response to pathogens. His discovery of DCs opened up the entire field of T-cell activation and has led researchers to study the therapeutic use of these cells for cancerous tumors and the development of dendritic cell-based vaccines for several viral infections, including HIV.

Steinman first discovered that it was dendritic cells that stimulated the immune system and propelled other T cells into action by studying cells derived from a mouse spleen. He noticed a novel type of cells, which had long branch-like projections, and therefore called them dendritic cells. These cells were found to induce T-cell replication and bolster the ability of T cells to kill pathogen—infected cells with a far greater proficiency—more than 100-fold-than that of B cells.

In later studies Steinman showed that dendritic cells harbor HIV and can transmit the virus to T cells, helping to spread the infection to other immune cells. This suggests that dendritic cells will play an important role in the development of preventive AIDS vaccines.

This year's Lasker Award for public service was given to Tony Fauci, director of the National Institute of Allergy and Infectious Diseases (NIAID), a division of the NIH, for his development of two public health programs in the US. Fauci was instrumental in helping to develop the US President's Emergency Plan for AIDS Relief (PEPFAR), which is a US$15 billion program to sponsor AIDS treatment and prevention programs in targeted developing countries. He also played a key role in Project Bioshield, which is a program designed to accelerate research into medical countermeasures to biological, chemical, or nuclear agents, such as a vaccine against anthrax.

Fauci has been director of NIAID since 1984 and was awarded the National Medal of Science earlier this year for his research on the pathogenesis of HIV (see An Interview with Tony Fauci).

The Lasker awards, often referred to as "America's Nobels," were established in 1946 and are awarded to scientists, physicians, and public servants whose accomplishments help alleviate major disease. Since 1962, 71 of the Lasker awardees have gone on to also receive the Nobel Prize. -Kristen Jill Kresge

AVAC Receives Large Grant to Advocate for HIV Prevention Research

The AIDS Vaccine Advocacy Coalition (AVAC) recently received a five-year, US$14 million grant from the Bill & Melinda Gates Foundation to support the organization's international advocacy efforts. This new funding will expand AVAC's focus beyond AIDS vaccines to include the broader field of HIV prevention research. AVAC now plans to step up efforts to advocate for several interventions that are currently being tested in clinical trials, including microbicides and pre-exposure prophylaxis (PrEP), which involves the use of antiretrovirals to prevent HIV transmission.

There are currently several ongoing Phase III efficacy trials that are separately testing both microbicides and PrEP, and AVAC plans to work with the communities that are involved in and affected by this research to help prepare them for the results of these trials. The organization, which is based in New York City, will also work to ensure that any benefits of this research become available globally.

Researchers establish new enrollment criteria for African volunteers

Researchers from IAVI, the US Military HIV Research Program (USMHRP), and the US Centers for Disease Control and Prevention (CDC) recently presented research at the AIDS Vaccine 2007 meeting in Seattle (seeSeattle sound) that suggests that a new set of medical criteria should be adopted to screen potential volunteers for AIDS vaccine trials in East and Southern African populations.

Healthy individuals who want to enroll in a preventive AIDS vaccine trial undergo routine medical screening to assess general health; blood chemistry and hematology are tested. The values are compared against a standardized reference range, typically one that has been established for populations in North America and Europe. Potential volunteers with lab values that fall outside the norms are excluded from trial participation.

Altogether, the research studies were conducted over two years and involved approximately 5500 healthy individuals from Uganda, Kenya, Rwanda, and Zambia. Researchers evaluated the blood chemistry and hematology parameters of healthy, HIV-uninfected individuals across seven different research sites to evaluate the kidney, liver, and immunological health of the potential volunteers.

For some of the clinical parameters there was a clear difference between what would be considered a normal result in a healthy African individual. Some of the most marked differences were in some of the baseline immune cell counts, including neutrophils, CD4+ T cells, and eosinophils. There was also a high percentage of Africans who had values for amylase, creatine phosphokinase, bilirubin, and hemoglobin outside of accepted North American/European ranges.

Establishing reference ranges that are relevant to local populations could help improve the enrollment process for clinical trials, including those of AIDS vaccine candidates, by reducing unnecessary exclusion. This could drastically improve the speed and ease of enrolling volunteers. In an AIDS vaccine trial previously conducted by USMHRP in Uganda, 58% of potential volunteers were unable to participate because their laboratory results were outside of the established reference ranges. When a second trial was conducted by USMHRP at the same site using the newly-established reference range, researchers excluded only 23%. Local reference ranges will also help researchers differentiate naturally-occurring laboratory abnormalities from any possible side-effects caused by the vaccine candidate or other intervention being tested. -Krsiten Jill Kresge

IAVI and DNAVEC Partner to Evaluate Sendai Virus Vector

IAVI recently announced a collaboration with the Japanese biotechnology company DNAVEC to develop and test a new AIDS vaccine candidate based on DNAVEC's Sendai virus (SeV) vector technology. This is the first time the SeV will be tested as an AIDS vaccine vector and the candidate developed by IAVI and DNAVEC will be designed to stimulate mucosal immune responses, which are thought to be critical for the development of a preventive AIDS vaccine.

SeV is an RNA virus that replicates in the respiratory system but does not cause disease in humans. The SeV vector is unique because it is a replicating vector, which researchers think may help improve its immunogenicity of the vaccine candidates. Preclinical studies of the SeV vector carrying genes from simian immunodeficiency virus (SIV) indicated that the candidate was able to protect non-human primates against infection with SIV. These studies were conducted by DNAVEC and the Japanese National Institute of Infectious Diseases (NIID).

The collaboration between DNAVEC and IAVI includes further preclinical testing of the candidate to collect more safety and immunogenicity data in non-human primates prior to conducting a Phase I clinical trial. Both IAVI and DNAVEC intend to advance the SeV-based candidate into human testing within the next three years. -Kristen Jill Kresge