STI Quarterly

Initiative for HIV vaccine research funded — Quest for a shot persists

Federal monies designed to accelerate vaccine development

Is development of a HIV vaccine still important with such established HIV prevention approaches as male and female condom use, voluntary medical male circumcision, and pre-exposure prophylaxis (PrEP) now in place to limit exposure to HIV and reduce infectiousness?

Federal public health officials say "yes." The National Institute of Allergy and Infectious Diseases (NIAID) has awarded $31 million in first-year funding to Duke University in Durham, NC, and the Scripps Research Institute in La Jolla, CA, as leaders of the new Centers for HIV/AIDS Vaccine Immunology & Immunogen Discovery (CHAVI-ID). The initiative is designed to accelerate HIV vaccine development.

"In recent years, considerable progress has been made in identifying antibodies that can prevent a broad range of HIV strains from infecting human cells," said Anthony Fauci, MD, NIAID director, in a release accompanying the announcement. The initiative is aimed at understanding how such antibodies and other immune responses work to protect against HIV infection, thereby aiding scientists to design an effective HIV vaccine, he noted.

The initiative is projected to receive up to $186 million or more over the next six years. By supporting multidisciplinary research into immune responses that prevent or contain HIV infection and generating model vaccine components that can induce these protective immune responses, scientists hope to accelerate HIV vaccine development.

Vaccine discovery and development takes time and money. An estimated $845 million was expended globally in 2011 alone.1 However, leaders from across the spectrum of HIV research who attended the September 2012 AIDS Vaccine 2012 Conference unanimously agreed on the need to continue the quest for an HIV vaccine. Myron Cohen, MD, director of the Institute for Global Health & Infectious Diseases at the University of North Carolina at Chapel Hill, said, "We recognize that suppressive treatment of HIV infection drastically reduces the probability of onward HIV transmission, which should eventually slow the spread of HIV, but the urgent and widespread treatment of HIV is not a substitute for a preventive vaccine. We need an HIV vaccine."

According to the Joint United Nations Program on HIV/AIDS, about 34.2 million people were living with HIV/AIDS in 2011, and the rate of new HIV infections continues to exceed 7,100 per day.2 In the United States, approximately 50,000 Americans become infected with HIV each year.3

Focus on immune factors

Duke University will receive $19.9 million in the first year for its role in the new program. Led by Barton Haynes, MD, director of the Human Vaccine Institute in the Department of Medicine at the university, the Duke team's work will focus on inducing broadly neutralizing antibodies that can prevent HIV-1 infection, as well as on generating protective T cell and innate immune system responses.

One strategy researchers will deploy is the evaluation of maturation pathways of broad neutralizing antibodies as they arise. The scientists will use these pathways as roadmaps for candidate vaccines to stimulate protective antibody responses. The program will encompass nine components: operations and management, genomics, lineage-based structural design, B-cell biology, neutralizing antibody development and sequencing, mucosal biology, virus biology, computational biology, and nonhuman primate testing.

The work will extend the work of Duke University's original Center for HIV/AIDS Vaccine Immunology consortium, whose federal funding grant ended in June 2012. Haynes led the initial group. "We were privileged to have the grant over the past seven years, and the work in this consortium helped us understand what needed to be done to make a successful AIDS vaccine," said Haynes, who also serves as director of the Duke Human Vaccine Institute and is a Frederic M. Hanes professor of medicine and immunology. "The CHAVI-Immunogen Discovery grant will be used to learn how to do what we need to do."

Antibodies, B cells eyed

The team based at Scripps Research Institute will conduct research on antibodies and B cells, the cells that make antibodies. This work will guide the development of immunogens (substances that evoke an immune response) that are capable of eliciting protective antibodies to HIV. Researchers also will focus on studying CD4+ T cells in an attempt to harness the cells' direct antiviral activity, as well as their ability to help B cells produce antibodies.

Researchers at Emory University in Atlanta also are working with the Scripps team. They are looking to understand the mechanisms of Tfh cell generation after immunization with HIV envelope (ENV) proteins and are identifying adjuvants that can enhance these T helper cells and also induce potent responses by B cells.

Five components are included in the Scripps program: operations and management, glycobiology (the study of the structure, biosynthesis, and biology of carbohydrates), nonhuman primate testing, concept-to-clinic discovery, and data management. The award provides an initial $11.1 million to the institute for the first year of work.

"We will work toward an HIV vaccine based on a deep understanding of the critical attributes of immune responses that provide protection against AIDS viruses, through these two focused and highly integrated efforts," said Scripps Research Professor Dennis Burton, PhD, who will head the La Jolla, CA, initiative. Burton also serves as scientific director of the International AIDS Vaccine Initiative's Neutralizing Antibody Center, at the Scripps Research Institute campus, and program leader at The Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, located in Charlestown, MA.

More research to do

Just one vaccine trial is under way. The HVTN 505 study began in 12 U.S. cities in June 2009 with NIAID sponsorship and funding. It is being conducted by the HIV Vaccine Trials Network (HVTN). The trial is testing a combination of experimental vaccines in men who have sex with men and transgender women in the United States. The trial is testing the safety and efficacy of a two-part HIV vaccine regimen consisting of one vaccine designed to prime the immune system, followed by another vaccine designed to boost the immune response

Additional studies are in the planning stages, including three studies to pursue improvement on the RV144 results in South Africa and Thailand; however, these are not likely to begin before 2014. The RV144 study, a six-year clinical trial, was the first to produce evidence of an HIV vaccine that showed some protective effect against HIV infection.4 The trial was sponsored by the Surgeon General of the United States Army and conducted by the Thailand Ministry of Public Health, with support from the United States Army Medical Research and Materiel Command and NIAID.

References

  1. HIV Vaccines and Microbicides Resource Tracking Working Group. What are vaccines for HIV prevention and therapy? Accessed at http://bit.ly/QXDW5q.
  2. Joint United Nations Program on HIV/AIDS (UNAIDS). Report on the Global AIDS Epidemic, 2010. Accessed at http://bit.ly/g8OHEr.
  3. U.S. Department of Health and Human Services. HIV in the United States. Accessed at http://1.usa.gov/MZTIWX.
  4. Rerks-Ngarm S, Pitisuttithum P, Nitayaphan S, et al; MOPH-TAVEG Investigators. Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand. NEJM 2009; 361(23):2,209-2,220.