Large Sum Awarded for Development of Protein Vaccine Candidate
A consortium led by the Bill & Melinda Gates Foundation awarded US$23.4 million to HIV co-discoverer Robert Gallo’s Institute of Human Virology (IHV) to support preclinical and clinical development of a DNA-based candidate that encodes a full-length, single chain (FLSC) fusion protein that targets the co-receptor CCR5. The immunogen is designed to induce antibodies to epitopes on gp120 known as CD4-induced (CD4i) epitopes, which are highly conserved across multiple HIV isolates. These CD4i epitopes are exposed immediately following viral fusion and persist for several hours.
“The area of the Envelope that interacts with CCR5 is internal and covered by a protein-folding carbohydrate that is mobile,” says Gallo. “Fix it, and it’s no longer mobile. If you link gp120 to the tip of CD4 that binds to the protein it opens and there is more room for antibodies to interact with gp120.”
IHV and its spinoff company, Maryland-based Profectus BioSciences, have studied a rhesus (rh) FLSC protein, and found that when rhesus macaques are immunized with this protein and then challenged rectally with the heterologous simian immunodeficiency virus/HIV hybrid strain SHIV162P3, they clear the virus more quickly and do not have long-term viral replication in tissues like the unvaccinated controls (1). The control of viral replication correlated with stronger responses to CD4i epitopes in the rhFLSC-vaccinated animals.
Gallo, IHV co-director George Lewis, and their colleague Anthony DeVico pioneered the FLSC protein. Gallo said he hopes to have the vaccine candidate ready for clinical testing in 15 months. The $23.4 million award, which will be spread over five years, includes $16.8 million from the Gates Foundation and $2.2 million from the US Military HIV Research Program (MHRP), which is partnering with IHV to move the vaccine candidate into clinical trials as quickly as possible. The Phase I and II trials will be conducted by IHV, MHRP, and Sanofi Pasteur, whose ALVAC-HIV vCP1521 canarypox vector-based vaccine candidate immediately sparked Gallo’s interest when the efficacy results of RV144 were announced in 2009 (see Raft of Results Energizes Researchers, IAVI Report, Sep.-Oct. 2009).
“The way Sanofi Pasteur designed the insert for its vaccine candidate was very interesting to me and my colleagues because they relied on some of the same key structural characteristics that we were using in developing our vaccine candidate,” says Gallo. “When I saw that the RV144 vaccine candidate had shown very high efficacy during the first year I was interested because that is exactly what we were seeing.”
At a meeting in New York, Gallo approached Nelson Michael, MHRP’s director, about collaborating. “There is a paucity of proteins right now and Gallo’s is one that shows a lot of promise,” says Michael. —Regina McEnery
1. Proc. Natl. Acad. Sci. 104, 17477, 2007
A Triumvirate of Leaders in HIV Vaccine Field Depart Posts
In June, three key leadership positions in HIV vaccine research and global health are being vacated.
In February, the Bill & Melinda Gates Foundation announced that Tachi Yamada would retire in June as head of the global health program. Yamada held this position for five years, during which the Foundation tripled its investment in its global health portfolio. Before joining the Foundation, Yamada was the chairman of research and development at the pharmaceutical company GlaxoSmithKline.
On June 24, Frazier Healthcare, a Seattle-based venture capital firm, announced that Yamada had assumed a position at the firm as senior executive in residence. According to the firm’s statement, Yamada will be splitting his time between Frazier and as a member of the board and advisor to the chief executive officer (CEO) of Japanese pharmaceutical company Takeda.
Seth Berkley, founder, president, and CEO of IAVI will also be leaving his post at the end of June to assume a new role as CEO of the GAVI Alliance, a Geneva-based global health partnership launched in 2000 to increase access to immunizations. After 15 years as the heart and soul of IAVI, Berkley will be joining GAVI at an exciting time. On June 13, the GAVI Alliance held its first pledging conference in London at which donors committed US$4.3 billion, exceeding GAVI's goal of $3.7 billion, to help scale up immunization programs in developing countries. According to GAVI, this will allow them to vaccinate more children faster and to accelerate introduction of new vaccines.
At the end of June, Alan Bernstein, the inaugural executive director of the Global HIV Vaccine Enterprise, will also depart his post. Bernstein served as executive director for three and a half years. During this time, the Enterprise established its headquarters in New York City, published a revised scientific strategic plan for HIV vaccine research, and established a young and early career investigators committee to discuss ways to attract and retain talented young researchers. Jose Esparza, senior advisor on HIV vaccines at the Bill & Melinda Gates Foundation, will serve as the interim head of the Enterprise. —Kristen Jill Kresge
New Foundation Established that Will Focus on Vaccine Research
Fourteen leading scientists, including several whose work is focused on HIV vaccine research, launched a new foundation to build greater support and increased funding for vaccine research. The Foundation for Vaccine Research, which will be based in Washington, D.C., aims to create global awareness for the need for increased, flexible, long-term funding for vaccine research.
The foundation grew out of a year-old effort known as the “It’s Time Campaign,” which started as an all-volunteer advocacy group in Washington, D.C. and was centered on AIDS, malaria, and tuberculosis. Those three diseases will continue to be the primary focus of the Foundation for Vaccine Research, but there are also plans to push for increased funding for all vaccine research efforts, including vaccines against neglected tropical diseases and influenza, says Peter Hale, founder of the “It’s Time Campaign,” and one of the leaders of the newly established foundation.
The leadership of the foundation also includes Galit Alter, an assistant professor of medicine at the Ragon Institute in Boston; Ronald Desrosiers, director of the New England Primate Research Center; Mauro Schechter, chief of AIDS research at Universidad Federal do Rio de Janeiro in Brazil; and Paul Offit, director of the Vaccine Education Center at The Children’s Hospital of Philadelphia.
Hale said the foundation hopes to organize a 2012 fundraiser, patterned after the “Stand Up To Cancer” telethon that resulted in pledges of more than US$80 million last year to accelerate cancer research. Hale said 100% of the pledges would be donated to vaccine research in the form of awards to individual scientists and laboratories. —Regina McEnery