The announcement yesterday that Seth Berkley will be taking the job of chief executive officer of the GAVI Alliance in August pulsed though the global health community. The GAVI Alliance, which faces a coming hurdle in raising the estimated $3.7 billion it needs to continue its global immunization efforts, has been without a CEO since the departure of Julian Lob-Levyt in October.

Berkley began developing the International AIDS Vaccine Initiative (IAVI) in 1994, and he has led the charge at the New York-based organization since it formally launched two years later. He’s seen the field through highs and lows, ranging from the disappointing STEP trial in 2007 to the more recent good news from the so-called RV 144 trial in Thailand, which in 2009 reported as much as 30% protection against HIV.

Nature Medicine caught up with Berkley today to hear what he has learned in his quest for a protective shot to stop the spread of HIV. What follows is a condensed version of the conversation:

This must be a bittersweet moment for you. What are your thoughts on how the HIV vaccine field has evolved?

I would say that I’m very excited about the field now, not only because of the Thai results, but we’ve [also] made enormous advances in the area of neutralizing antibodies over the last 18 months and now have many, many targets on the virus as well as antibodies that neutralize all of the strains at incredibly low doses. The science is in fabulous shape.

Looking back, how would you guess that we should start thinking about combining approaches to HIV vaccination?

At the end of the day, what you want is a vaccine that provides both neutralizing antibodies and cellular immunity. That’s what the best of other vaccines do, and certainly given the variability of this organism if you could only have one of those you’d probably want neutralizing antibodies because of the fact that neutralizing antibodies can block acquisition. Of course, to do good neutralizing antibodies you have to have T helper cells. But in terms of having an ability that if some of the virus was to get through, to have a way to mop that up with cell-mediated immunity would be important.

What are going to be the main challenges for people to look to in the next year for the HIV vaccine field?

I think one of the big challenges is the whole area of rationally based vaccine design; it’s relatively new, it’s untested and we’re working our way through that.

What do you mean by rational design?

One of the interesting things about the work on neutralizing antibodies is that it’s a retro vaccinology approach. What were talking about here is, we’ve already got the antibody, the question is, ‘What is the antigen that can induce that antibody?’ We normally go the other way. In this case we’ve got it, and we’ve got to work backwards.

Some people have voiced concern about the disproportionate amount of research funding going toward HIV as it relates to disease burden in the world. How is that going to figure into both HIV vaccine research and the vaccination field going forward?

AIDS appeared out of nowhere. It’s so far killed upwards of 25 million people; there’s another 33 million infected today. The world now spends about $50 billion a year dealing with this pandemic and that’s not enough because 60% of people in the developing world who have HIV are still aren’t getting treatment. [We] desperately need better prevention, and the best prevention we could have would be a vaccine.

Advance market commitments (AMCs) are used to fund vaccine campaigns. What would be the advantages and disadvantages of using AMCs for HIV vaccine development?

There are really two types of funding: there’s push funding and pull funding. Push funding would be to drive the research forward, to pay for it, to get people engaged. Pull funding would be to put a financial pot out there and use that as a way to engage people in it. The pull funding [approach] works much better when you’ve got proof-of-concept and people know that if they invest the money something will happen and they can potentially succeed. It’s harder when you go upstream.

Do you think it’s time now for that pull mechanism approach for HIV vaccine research?

I think we’re getting close. It probably isn’t time yet because [although] we have proof-of-concept that a vaccine is possible, we don’t yet know how to get it to the level we need for it to become commercially feasible. Once we crack that problem, then I think it’s a great time to use a mechanism like that.

Obviously you’ve had success with fundraising at IAVI. And GAVI potentially faces challenges in raising the $3.7 billion it’s hoping for in June. What would you say you’ve learned since 1996 in terms of what it takes to convince donors to give?

It’s very different for AIDS vaccines than for conventional vaccines. For AIDS vaccines, the real challenge was to convince people that this was a priority even though the science wasn’t yet there. The science is moving now, so it’s much easier now to say to a donor it’s really a time to invest because progress is happening. For existing vaccines, vaccines are the most cost-effective intervention you can do. I think our challenge is to sell this as the right thing to do, given it’s cost effective and the given the number of lives that can be saved.