In Brief

Chief Science Officer of IAVI departs to lead Human Vaccines Project

After nearly 17 years at the helm of the research and development program at the International AIDS Vaccine Initiative (IAVI), Wayne Koff left his full-time role as Chief Science Officer at the organization in March to assume a new role as President of the Human Vaccines Project (HVP). This recently formed non-profit venture is focused on rational design of vaccines against a variety of challenging pathogens.

Koff’s work with HIV began in 1985 in academia. The virus, and stopping its spread through vaccination, became a thread that has run throughout his career in government, industry, and the non-profit sector. Koff joined IAVI in 1999, three years after the organization was founded, and is only the second person to head its research and development department. Margaret Johnston was the organization’s founding Vice President of Scientific Affairs.

Koff recalls that time in IAVI’s history as an exciting one. “At the beginning IAVI had the enthusiasm, naivety, and the energy of being a brand-new idea,” he says. “We were on a ramp-up phase for a number of years. As the funding increased, the opportunity increased.” IAVI’s founder Seth Berkley, who served as chief executive officer until 2011, brought Koff on board to lead the organization’s growing interest in research and development. Dennis Burton, scientific director of IAVI’s Neutralizing Antibody Center and an immunologist at The Scripps Research Institute (TSRI) in La Jolla, California, recalls the combination of Berkley’s leadership and Koff’s innovative nature as a potent one. “I think those two complimented each other greatly. Seth was very charismatic and inspirational and Wayne was a visionary with the science,” says Burton. “The two of them together were a formidable force.”

During his tenure at IAVI, Koff oversaw several initiatives that opened the door for researchers to pursue many of the vaccine strategies that are being explored today. One of these initiatives was creating the Neutralizing Antibody Consortium (NAC) in 2002. The NAC was created to address what Koff saw as a fundamental challenge to HIV vaccine research: the elicitation of antibodies that could neutralize a broad swath of HIV isolates, so-called broadly neutralizing antibodies (bNAbs). But at that time, this was not the common view among researchers. “Wayne was visionary in his thinking about the Neutralizing Antibody Consortium. He saw neutralizing antibodies as the future of HIV vaccines at a time when virtually everyone was looking to T cells,” recalls Burton. That has since changed. Burton, who just returned from the recent Keystone Symposium on HIV vaccines, says two thirds to three quarters of the vaccine presentations at the conference were on antibodies. “When Wayne started the NAC it was about 10 percent,” according to Burton.

The NAC began with six or seven investigators focused on different aspects of neutralizing antibody research and then expanded from there. At its largest, the consortium brought together as many as 26 investigators to work collaboratively on eliciting bNAbs against HIV.

Burton also views establishment of the IAVI Neutralizing Antibody Center in 2009 by IAVI and TSRI as another coup that has greatly influenced the current shape of the science. “Wayne was the real driver of this. He really steered IAVI into supporting this,” recalls Burton.

After its establishment at the Scripps campus in La Jolla, the Neutralizing Antibody Center was able to recruit top talent, including researchers William Schief, Pascal Poignard, and Richard Wyatt. “I had the ability to identify and hire people who were a lot smarter than I was and that helped create an R&D team that really contributed to the field,” reflects Koff. Burton agrees and says that these hires “accelerated great progress.”

Koff can also be credited with innovative epidemiology studies that are continuing to guide vaccine design efforts today. Koff is responsible for driving IAVI’s Protocol studies, which helped researchers gain a better understanding of HIV disease among African cohorts as well as the immune responses that develop in response to infection, and also allowed researchers to identify the types of bNAbs that researchers surmised would be vital to vaccine-induced protection. During one of the Protocol studies, researchers collected samples from thousands of HIV-infected volunteers in Africa, India, Australia, Thailand, the UK, and the US. These samples are proving to be a treasure trove for vaccine researchers. In partnership with biotech companies, IAVI and its partners in the NAC were able to isolate dozens of very potent and broadly neutralizing antibodies from these samples. Identification of these antibodies then led to identification of multiple targets on the virus that were not identified previously. Burton calls the collection of these samples “absolutely crucial to the vaccine field.” The antibodies isolated from these volunteers and the viral epitopes they target, are now the basis of much of the HIV vaccine design and development efforts taking place in labs around the world (see image at right). “The knowledge that has been gained on the HIV Envelope on the molecular level and the knowledge that has been gained with the antibodies is like an inflection point in the field,” says Koff. “We know so much more now.”

Burton also credits Koff and IAVI with being able to create partnerships with biotechnology companies to advance antibody discovery efforts. “Those interactions led to what many people do today but was all started through the ability of IAVI to move quickly on its feet and interact with these biotech companies. Wayne really orchestrated a lot of that,” adds Burton.

Other contributions include Koff’s oversight of a team that established the Human Immunology Laboratory (HIL) at the Imperial College of Science, Technology, and Medicine in London, and the development of a network of clinical research centers in East and Southern Africa that performed some of the first HIV vaccine trials on the continent. Jill Gilmour, executive director for human immunology at IAVI and principal investigator of the HIL, can enumerate Koff’s contributions and attributes, as well as his unwavering commitment to AIDS vaccine research. “On a personal level I know Wayne believes deeply in the mission,” says Gilmour. “Wayne has scientifically, and otherwise, challenged himself, IAVI, and the field to tackle major road blocks and to do the right thing and not just what is on trend.” This was particularly true with the establishment of the clinical research centers in Africa. “This challenged the accepted norm and broke through barriers,” recalls Gilmour. “It helped ensure vaccines are tested rapidly in relevant populations and these expert Phase I/II centers now provide access to unique cohorts and samples that are driving vaccine innovation.”

Koff will no doubt be employing similar innovative ideas at the HVP. This non-profit organization started from an idea hatched together with vaccine veterans Stanley Plotkin of the University of Pennsylvania and Ian Gust of the University of Melbourne. The project involves deciphering the human immunome—creating a detailed map of the genes and proteins associated with the human immune response to vaccine antigens—through a series of clinical research studies. This will, in turn, help elucidate the rules of protective immunity and thereby fuel the rational design of vaccine candidates against HIV, influenza, cancer, dengue, and other infectious pathogens.

At the human vaccines project Koff says he’s “right in the middle of the excitement of a new idea,” much like when he joined IAVI. He remains confident that a vaccine against HIV will be developed, eventually. “This is a virus that has found a number of methods of immune evasion, but it is still a virus. It can be blocked and controlled. These are solvable problems.” —Kristen Jill Kresge