Vaccine Briefs

First US National AIDS Strategy Aims to Cut New Infections and Optimize Care

US President Barack Obama’s administration released the nation’s first National AIDS Strategy in July that pledges to reduce the number of new HIV infections by 25% within five years. The 60-page report, which was prepared by the White House Office of National AIDS Policy (ONAP), also aims to increase access to care and optimize health outcomes for people living with HIV/AIDS, and reduce HIV-related health disparities by reducing stigma and discrimination.

Approximately 55,000 Americans are newly infected with HIV each year, an estimate that epidemiologists say has remained static for the past 15 years, despite ongoing efforts to try to reduce HIV incidence rates. The US Centers for Disease Control and Prevention estimates that there are now more than one million people living with HIV/AIDS in the US, and that about a fifth of them are unaware that they are HIV infected. The National AIDS Strategy aims to increase the percentage of people living with HIV who know they are infected from 79% to 90%. The strategy also mentions the need to develop, evaluate, and implement a combination of effective HIV prevention strategies, including AIDS vaccines and microbicides, as well as strategic use of syringe exchange and expanded HIV testing to reduce HIV transmission rates.

The Obama administration has designated six federal agencies to execute the strategy and has given the agencies a deadline of January 2011 to submit a report to ONAP and the Office of Management and Budget on the operational plans for implementing the strategy.

US spending for HIV/AIDS programs and services will remain flat in the proposed 2011 budget that kicks in October 1, 2010. This prompted some AIDS advocates to wonder whether the National AIDS Strategy will ultimately be able to have any meaningful influence on the domestic response.

Mark Harrington, executive director of the Treatment Action Group, a New York-based AIDS research and policy organization, says he thought the US aim of reducing new infections by 25% within five years wasn’t nearly aggressive enough. “If we really did a good job, we could reduce infections by 50% and really make an impact,” says Harrington. “This strategy shows a lack of ambition and a lack of resources. I think we need presidential leadership on this, but Obama hasn’t done that, and I’m disappointed. This is not a strategy to end AIDS, this is a strategy to manage AIDS.”

Jeff Crowley, director of ONAP, said during a July 18 session at the XVIII International AIDS Conference in Vienna that the US already provides more than US$19 billion in annual funding for domestic HIV prevention, care, and research programs. “We believe we can make significant improvements with existing resources,” said Crowley, who moderated a discussion about the community response to the strategy.

Leading up to the release of the strategy, Crowley said the Obama administration held 14 discussions attended by more than 4,000 people within the AIDS community, and issued an “online call to action” that received more than 1,000 recommendations.

Judy Auerbach, vice president of Science & Public Policy at the San Francisco AIDS Foundation, was one of the founders of the Coalition for a National AIDS Strategy that secured a commitment from Obama to develop such a plan when he was seeking the presidency. “It was striking, not just to Americans, but to the rest of the world that we did not have a singular plan,” says Auerbach. “So from my point of view, it’s really encouraging that it happened as quickly as it did. I think the plan is quite good in terms of its specificity.” —Regina McEnery

Vaccine Candidate Targeting Dendritic Cells Enters Clinical Trial

Scientists at Rockefeller University in New York City began testing a novel AIDS vaccine candidate in July that specifically targets dendritic cells in the lymph nodes and other organs of the immune system.

The vaccine candidate contains a monoclonal antibody (mAb) engineered to recognize DEC-205, an endocytic protein found on the surface of dendritic cells that mediates efficient presentation of antigens. DEC-205 was discovered 12 years ago by Michel Nussenzweig, who is head of the laboratory of Molecular Immunology at Rockefeller University. Dendritic cells themselves were co-discovered at Rockefeller in 1973 by Ralph Steinman, the Henry J. Kunkel Professor and Senior Physician of the Laboratory of Cellular Physiology and Immunology at Rockefeller, and his colleague, cell biologist Zanvil Cohn, who died in 1993.

The mAb is fused to an HIV clade B p24 Gag protein. Gag p24 was selected as the vaccine antigen because of its many conserved epitopes, which may induce greater breadth of CD8+ T-cell responses.

 

Red fluorescent image of dendritic cells in skin with en face staining. Image courtesy of Rockefeller University

The three-year, randomized, placebo-controlled, Phase I trial, known as DCVax-001, will enroll 45 healthy HIV-uninfected volunteers in New York City. Investigators will evaluate both the safety and immunogenicity of the vaccine candidate administered at three different doses, along with a fixed dose of an experimental adjuvant called Poly ICLC (Hiltonol) that was designed to activate innate immune responses. The volunteers will receive three subcutaneous vaccinations of either the vaccine candidate or placebo over 12 weeks, and will then be monitored for 12 months.

Researchers at Rockefeller have been working with Celldex Therapeutics, a biotechnology company headquartered in Massachusetts, on the development of the candidate vaccine. Celldex previously developed a vaccine candidate with a mAb fused to DEC-205 to target a tumor-associated antigen known as NY-ESO-1, but this is the first time an AIDS vaccine candidate has been constructed using this technology.

The experimental adjuvant Hiltonol was developed by the pharmaceutical company Oncovir, based in Washington, D.C. It induces the production of interferon, which interferes with viral growth. Hiltonol was previously evaluated in therapeutic vaccine studies for brain tumors. More recently, researchers have been eyeing Hiltonol as an adjuvant for prostate cancer vaccines. This adjuvant has also demonstrated the ability to improve the capacity of dendritic cells to recognize and present certain viruses, such as Ebola virus and poxviruses, to the immune system, leading researchers to consider using it as an adjuvant in preventive vaccines.

Green fluorescent image of a splenic dendritic cell taken from a mouse. Image courtesy of Rockefeller University.

 

In the DCVax-001 study, Hiltonol is used to help immature dendritic cells—whose job it is to scoop up antigens—mature and present the antigens to CD4+ T cells and B cells. Sarah Schlesinger, the trial’s principal investigator, says this candidate vaccine regimen performed well in experiments in Indian rhesus macaques, although she did not disclose specific details because the nonhuman primate findings will be published soon.

Jacques Banchereau, director of the Baylor Institute of Immunological Research in Texas, is developing a therapeutic HIV vaccine candidate that targets dendritic cells. However, the Rockefeller study is the first time a dendritic cell-focused approach is being tested as a preventive HIV vaccine candidate. —Regina McEnery