Emilio Emini: [00:00:00] Thank you very much, Dan [Barouch]. Thank you to the organizers, as everyone else said, for the honor, for the invitation. It's been really incredible sitting here for the last two and a half days, and it's certainly a lot more incredible than anything I'm going to say in the next 20 minutes. I was asked to talk about the challenges in vaccine development. I always get asked to talk about challenges in vaccine development, and so I'm not going to do it. [00:00:30] [laughter] I changed the title. That reflects the concept of challenges in vaccine development which is as far as HIV vaccine development is concerned, will the future be any easier than the past? The bottom line answer is no, but bear with me. A lot of what you're going to hear me say, actually, as I go through a lot of the background here, actually, Bart said in much, much more detail during the immediately preceding talk.
Let me tell you how I wound up doing what [00:01:00] I wound up doing with respect to HIV. I'm going to go back 40 years when I was a graduate student at Cornell Medical here in New York City. I'm a native New Yorker, grew up in Manhattan. I was working on a Venezuelan encephalitis virus. I was doing pathogenesis work in Venezuelan encephalitis virus. No one remembers any of that work that I did back then when I was a graduate student, and I don't remember any of the work [00:01:30] that I did when I was back there as a graduate student. Seriously, if you asked me to look up what the papers were, I'd have to look it up to see what I was doing. What that did allow me to do, the Venezuelan encephalitis virus was considered to be a class 3 pathogen, so I had the opportunity to spend five years essentially working in a class-3 pathogen laboratory.
When I left Cornell after my PhD, I went actually at the Stony Brook to do a postdoc with Eckard Wimmer (b. 1936) on poliovirus. [00:02:00] This was a very unique time actually because it was mid-1980 when I joined. This was at a time when the primary structure of the poliovirus RNA genome, which was a big deal, obviously, back then in 1981, had been determined at David Baltimore's laboratory, and they did it at the same time. (1) What this allowed me and my colleagues to do in Eckard's laboratory is have a tool available really for the first time to do some in-depth study of poliovirus which, of course, have been around [00:02:30] and considerable interest since the days of the polio vaccine had been developed.
This was also one of the new tools which had just become available in those days was monoclonal antibodies, mouse-derived monoclonal antibodies. I spent essentially three years of my postdoc trying to understand the nature of antibody-based or antibody-dependent neutralization of poliovirus, which is the basis of the [00:03:00] efficacy of the poliovirus vaccine. I did that on a structural basis, and all sorts of work, published a fair number of papers. (2) This was the first time that we actually defined some of the structurally-defined poliovirus neutralization epitopes at the time.
Actually, at one point, we published a paper which showed that we could induce—we could prime for and we could induce anti-poliovirus neutralizing antibodies using synthetic peptide immunogens as opposed to using the whole virus. (3) Now, why am I telling you all this? I'm telling you all this because this was my [00:03:30] context and my background when I then stopped and finished my postdoc and went on to the Merck Research Laboratories.
I wound up at the Merck Research Laboratories back—it was in 1983 and it was, again, like most things in life, pure luck. At the time, Ed Scolnick, who had come up from the NIH, moved to the Merck Research Laboratories to take on a role that ultimately became the role of head of the research laboratories where Roy Vagelos (b. 1929) [00:04:00] moved down to be the president and CEO of Merck & Co. As part of Ed Scolnick moving into Merck, he was given a number of open positions to fill up. Ed Scolnick decided, "I'm going to go look for a bunch of hotshot postdocs and we're going to bring in people coming off their postdocs and we'll put them in here." His definition of that was to call up people and say, "Do you have any postdocs available that were just finishing their postdocs?" That just happened to coincide with the time that I was actually looking for a position. [00:04:30]
The alternative to actually going to Merck was actually winding up here at Cold Spring Harbor, but I decided I wanted to go to Merck because, even though Ed Scolnick had just joined and Maurice Hilleman (1919–2005), who many of you know obviously is the grandfather, we'll call him that, of a lot of vaccine work that was done and he was very interested in vaccines emanating obviously from this work. Maurice Hilleman had made the decision. He was going to stay at Merck in an emeritus position, and the opportunity to work with Maurice Hilleman to learn about what vaccines really are and what you do with them was just something you [00:05:00] just couldn't turn down, so I decided then to go to the Merck Research Laboratories. I joined in 1983 and worked on the early recombinant hepatitis B vaccine, started the program that ultimately led to the development of the current hepatitis A vaccine. That brings us to 1986.
In 1986, both Roy Vagelos and Ed Scolnick got together and said, "You know, we've got to do something with respect to HIV." HIV, [00:05:30] as you all have heard over the last few days, when, those years, was clearly a disaster in the process of going on. Remember, this was at a time when many pharmaceutical companies were actually run by scientists, which is very different than the current days. Therefore, Roy and Ed decided this was something which was worthwhile doing. The first thing Ed did was to figure out, "Okay. Who's going to do this work?" I was the only trained virologist in the company, believe it or not, at the time and, certainly, the only one who had any experience working with a class 3 [00:06:00] pathogen. I remember the day he came to me and he asked me, "Do you want to do it?" Obviously, if you're going to be a virologist, and still a young scientist at the time, you just simply don't turn down that opportunity obviously.
So I started to work in HIV research and we opened up two programs. One was a vaccine program and the other one was a program to potentially define novel antiretroviral agents. I'm not going to talk about the latter, but I will talk about because I've been asked to talk about what we do with vaccine. Actually, [00:06:30] this paper—Bart [Haynes], you put this paper up. (4, 5) We were focused on—except, I think, you stopped halfway through and you said, "et al.," so you missed where my name was there where we worked on— [laughter]
I should mention one thing. Let me tell you how I get my hands on the virus, to actually bring it to the laboratory to work because there's a story of Bob [Gallo]. Bob was very gracious. I remember Ed and I actually called you up. We came down. You probably don't remember. We came down to the NCI and met with you and we talked about the potential of, you know, [00:07:00] "Could we get a sample of the virus from you so we could start to work in the laboratory? Several weeks later, I called you up. You said, "Come on down. I'll give you a sample." I got in my car. I drove down to I-95. The Merck labs are just outside of Philadelphia. I drove down to Bethesda, came up to your laboratory. You gave me a spinner flask, a glass spinner flask, with H9 cells that were producing [HTLV]-IIIB. I took it, put it in a cardboard box. [00:07:30] Back in those days, I was driving an old hatchback Toyota, stick shift, four-cylinder, no power. I put the flask in the spinner flask, put it in the back of the car, and I drove up I-95 right back to Philadelphia. I will leave it at that. [laughter]
Anyway, it was the start of a lot of work that we did. Given the interest, obviously, in peptide-based vaccines that I had done with poliovirus, obviously, working with a group of colleagues here looking at the so-called HIV-1 principal [00:08:00] neutralizing determinant which, obviously, as Bart mentioned, turned out to be the V3 determinant. This was a figure from the paper where we looked at a number of different peptide sequences and had the very early naive concept back in those days of, why can't we elicit neutralizing antibodies by simply making a whole series of peptides that can cover a whole diverse potential panel of V3 sequences?
Now, what we did in addition to just looking at the peptides, focused on, could we, in fact, neutralize [00:08:30] this virus in vivo with anti-V3 antibody? (6) Remember, in these days, we were capable of working with chimpanzees. This was an in vitro study where we took the anti-V3 antibody in vitro and then mix it with a virus and then use it to challenge chimpanzees. This was the first demonstration, at least in vivo, that neutralizing antibodies, albeit to the V3 determinant, could, in fact, have a biological effect. We had this old anti-V3 monoclonal [00:09:00] antibodies, some of you may remember 0.5β that showed partial protection, and then a IIIB-specific anti-V3 polyclonal antibody that showed complete protection relative to control. In those days, you were looking for seroconversion to see if you picked up an infection. We then went on subsequently and did this in vivo by actually trans—to giving the antibody itself to chimpanzees prior to challenge, and then [00:09:30] challenge the animal, and then show that, in fact, we could protect. (7)
This was the first demonstration of this that we had. As Bart mentioned in his previous talk, this was all nice and good. This was published in, as you see, in the latter part of 1991. But this was just at the time that a very large number of investigators, including David Ho and others, showed that this was a phenomenon that was very specific to virus variants that have been adapted to continuous growth in lymphoid cell cultures and the primary assets of the virus, which is simply fundamentally not susceptible [00:10:00] to anti-V3 neutralizing antibody. So that pretty much put a stop to this particular line of investigation.
But as it turned out, the other thing I was doing at the same time was working on the development of antiretroviral agents. One of the ones was a non-nucleoside reverse transcriptase inhibitor L-697,661, which was never ultimately fully developed, but we did bring it forward into a clinical study in collaboration with Mike Saag (b. 1955) and George Shaw [00:10:30] down at UAB (University of Alabama at Birmingham). (8) This was a study in which—and Doug Richman mentioned this yesterday, where we showed—and this was in patients who are HIV-positive, obviously, who received compound as a monotherapy. And here, we're looking at p24 antigen levels because this was before we had the viral RNA assays. What you saw here was an initial decline and then a very, very rapid rebound that was associated with this.
I remember that [00:11:00] a number of people didn't believe that the only obvious interpretation to this was the fact that we were selecting for a resistant virus and we fairly quickly showed this. Doug was doing parallel work as he mentioned yesterday with another non-nucleoside RT inhibitor nevirapine (NVP). Essentially, this was very interesting. We had no place to go as far as the vaccine program was concerned. I spent the next four to five years working almost exclusively on antiretroviral therapy, understanding resistance patterns that are non-nucleoside RT inhibitors, and then being involved in the [00:11:30] development of indinavir and then also efavirenz (EFV) at the time. That ultimately culminated in the Merck 035 study that Doug showed yesterday, which was a triple combination study that was presented in 1996.
When that was done in 1996, I was asked to take on the head of the vaccine research at Merck, which is something why I had originally come to Merck so many years before hoping to be in that position which I ultimately got there, [00:12:00] though I got there without working on vaccines, which was an interesting thing. We started working on a number different vaccine programs. Some of which, luckily enough, turned out to be successful. The development of the papillomavirus vaccine, the development of the rotavirus vaccine. Colleagues and I, we worked together collaboratively on all of those programs.
I also continued to work on HIV-1 and this time turned my attention to the potential of vaccines that would elicit [00:12:30] cellular immune responses or T cell responses that at the very least, if not prevent infection, could control infection. There were obviously a number of publications. This is just a small smattering. I picked this particular figure for a reason. The reality is this started with the original observation from Rick Koup (9) and then, of course, all the work that was done by Bruce Walker and others during this period. (10, 11, 12, 13, 14, 15, 16, 17, 18) What I wanted to point out was one particular study, which was a study that was a [00:13:00] non-human primate study done by Dan and Norman Letvin (1949–2012).
You probably remember this back in those days, Dan [Barouch]. You published this in 2000. (19) This is an interesting study, which looked at using a plasmid DNA that was expressing, if I remember correctly, with pol and env, that was then delivered with IL-2 (interleukin-2) and you got a very good little immune response as anticipated. The challenge here was SHIV 89.6P [00:13:30] and the suggestion was—the data were actually were pretty clear—that in fact, you could control the initial viremia and the level of virus during the persistent phase of the infection in the immunized animals.
So I and my colleagues then went on. Following on with this, we did the work which was, in this case, focusing only on the internal proteins which was Gag, using a replication-incompetent adenovirus type 5. We picked adeno type 5 because this was, in fact, the delivery system that was [00:14:00] fairly well understood at the time. In fact, when we did this study, we also used DNA. We also used MVA as well in the study. Let me just take one figure from this. Now, this was a study which we immunized animals. As you can see, we did a number different immunizations.
I'm just going to draw your attention to the bottom of the figure here, which is where we used DNA expressing Gag followed by adenovirus type 5, replication-incompetent vector expressing gag. Just look at the naive [00:14:30] controls. What we got here on the left-hand panel here, these are the CD4 T cell counts subsequent to challenge and here is the viremia on the right. Of course, every line, there's a single animal. Now, what we did in this study—and, admittedly, we put our thumbs on the scale on this one. These are all Mamu-A*01(+) animals, so likely to make a cellular immune response. This was, again, SHIV 89.6P.
Now, the thing about SHIV 89.6P is that as many of you know, it has a [00:15:00] very negative effect on CD4 cell counts if you see your naive controls and, therefore, some fairly high viremias that subsequently occur. Any initial protection against the effect on the CD4 cell counts is going to actually be manifested in a pretty substantial viremic effect both in terms of the declines, substantial decline—this is, of course, the log scale—Substantial decline in the peak viremia and then, obviously, in the persistent phase viremia.
This is what [00:15:30] led us to—Let's see what happens if we can take this and can take it on to a subsequent clinical study. Now, at the time we published this paper in Nature, Dan and Norm had a follow-on paper that was published back to back, which was a follow-on from the original study that they did use using DNA and IL-2 where they demonstrated that after a period of time, at least a subset of these animals developed escape from the [00:16:00] cytotoxic T lymphocytes. (21) We have these two papers. In fact, there was a News & Views article that was written by Jeff Lifson and Mal Martin. (22) They came up with this title that same issue, which was "AIDS vaccines: One step forwards, one step back," which obviously was quite true.
We took a look at that and we decided to do one more set of studies. (23) This time, instead of using 89.6P, we looked at the [00:16:30] DNA and recombinant adenovector vaccine again expressing gag. Except this time, we did it in monkeys that were both Mamu-A*01(+) and another subgroup that were Mamu-A*01(-). Here, the challenge was SIVmac239. In this study, obviously, the results were somewhat different. Here are the Mamu-A*01(+) animals. These are the CDA responses, so we can leave this and let's go for a while. If you take a look at the viremia that occurred after challenge, [00:17:00] here's the control.
Here's where we had the best immune response, which is DNA followed by adeno. In fact, which you can see again, it's a lot of scale. It's a little bit difficult to see, but there was a consistent effect on the peak viremia and, to a certain extent, releasing some of the animals on the prolonged phase of the viremia. However, if you did the same thing in the Mamu-A*01(-) animals, you really couldn't tell the difference between the immunized animals and the control animals.
Nonetheless, [00:17:30] the decision was made to take this forward into a human clinical study. I'm going to come back to this theme a little bit later in the talk, because there comes a point in the end where what one needs to do is to essentially take a deep breath, do the human clinical study. But you got to do it in a way in the end where you've designed the study in such a way that if you do get a negative result, you can actually clearly interpret the results.
This led to the STEP study (2004–2011) and [00:18:00] we all know the results of the STEP study. (24) I actually borrowed this figure from a review that Dan wrote not too long ago. (25) I like this figure because it's a clean figure. What you'll recall what happened in the STEP study is that, in fact, not only was there no protection comparing placebo to the vaccines, but in individuals who had a preexisting immune response to the adeno vector, there was what appeared to be—no, not appeared to be but in fact was—a higher likelihood of infection in the vaccinated group as opposed to the [00:18:30] placebo group. In fact, there was some indication that the higher the preexisting antibody response to Ad5 and presumably, therefore, the higher preexisting immune activation that occurred as a result of giving the adeno vaccine, the higher the likelihood that one would become infected.
What this did—and Bart in his previous talk referred to this as a failed study. My apologies. I don't know if Bart is still here, but my apologies, I would not refer to it as a failed study because in the end, it [00:19:00] did teach us that this part of the concept was not going to work. All right. It also taught us something else which something that, Bob, you mentioned a couple of times already. You have to be careful about that initial immune activation because I'm almost convinced that, even though the data aren't fully solid about it, but there's no other interpretation in my mind for this, that what we were looking at here was an immune activation that occurred in people who have been previously exposed to adeno 5. The adeno type 5 vector, I will tell you, is a very strong immune [00:19:30] activator. As a result, we wound up potentially eliciting a situation where there were a larger number of susceptible cells that were present in these individuals at the time that they were exposed to HIV. Something to be cautious about. Not something that's going to prevent us from doing additional clinical studies, but something to be cautious about when managing those clinical studies. At any rate, this is an approach that didn't work and we put it away.
Just like when [00:20:00] neutralizing antibody responses to V3 were shown probably not to be of importance, I decided I was going to concentrate my time and effort instead on studying antiretroviral agents. As soon as these results appeared to be the case—actually, right before these results because it almost didn't matter what was going to happen—I decided I'm going to change career path, which I did. I left the Merck Research Laboratories, somewhat for a changed career path, I left the [00:20:30] Merck Research Laboratories because, by this time, I'd been there for 22 years. 22 years in a single institution is not a good idea for anybody. I left the Merck Research Laboratories.
I actually went on to IAVI (International AIDS Vaccine Initiative) because what I wanted to do at IAVI is that I really wanted to see what the real world was like as opposed to the world inside a company all the time. I was fortunate enough when I was at IAVI to be involved in some of the earlier work that led ultimately to the establishment of the cohorts that Dennis Burton talked about, the so-called Protocol G cohorts. Those were designed [00:21:00] while I was there in that organization.
And then I completely left the field because I actually spent enough time working at IAVI to realize that while HIV was a significant problem, in many parts of the world, pneumococcal infection, particularly of infants, is an extraordinarily difficult problem. A pneumococcal conjugate vaccine had been available for many years but didn't have the appropriate serotype composition for use in the developing world. So I was asked [00:21:30] to come to—at that time, it was Wyeth that ultimately was acquired by Pfizer to help develop the 13 mil of pneumococcal conjugate vaccine. When I joined, I figured this was going to take four or five years to do. It took actually 10 years to do to develop the vaccine successfully for both pediatric and for adult use.
Anyway, be that as it may. That brings us up to about two years ago when I then had the opportunity to join the Gates Foundation. [00:22:00] In the last three or four minutes, very quickly because Bart went through a lot of this. A lot of what continued to go on in HIV vaccine research, I was living vicariously looking at it from quite a distance because I was no longer working in virology. I was actually working on, of all things, bacteriology, which just goes to show you you don't really need to know what you're doing to do a good job on things. I did that for a while, but a lot of work continued.
You're all familiar with the work that [00:22:30] Dan has done with different adenovirus vectors. (26) This was one of the original studies. This was with two adenovirus vectors. This was the study that was done with both MVA and adeno 26. (27) This was the published study. Here, you can see this here, we had a challenge. This was SIVmac251 challenge. It was an intra-rectal low-dose challenge. You can see the effect right here, the 1Cs with Ad26 containing vaccines in different combinations compared to the control [00:23:00] vector. The interesting thing here is that this appears to be an effect that depends on the presence of the envelope gene being expressed by the Ad26. The basis of the immune response for this other than saying it is an immune response clearly to envelope, but the functional basis of the immune response, and Dan you can correct me if I'm wrong, is not yet well understood. A number of hypotheses out there and going back to some of the previous discussions, but it's not well understood.
We of course then also—this was the original [00:23:30] RV 144 study (2003–2009) that was done. (28) Again, the appearance of protection with a lot of work that was done in retrospect to try to figure out what the immune correlates of protection are here. Again, quite frankly, in the end, the real basis of this protection if it's real is not well understood yet. There's that. Of course, this is the work that was referred to earlier that Louis Picker did with the CMV vector expressing gag. (29) Approximately, [00:24:00] 50% of the challenged animals appear to clear the infection and clear it persistently. This has been a consistent observation by Louis and his colleagues.
These are at least three interesting systems here. The original RV 140 or the RV 144 observation that was done using ALVAC and gp120, the work that's been done with the adeno 26 vector. This work done with the CMV vector where the questions are, Do we really fundamentally understand what the immune base—it's not neutralizing [00:24:30] antibody as we were discussing previously. This may be an unusual, I'll use that term, cellular immune response associated with this one. It's that data are suggestive. It's not fully definitive yet. The question is in the end. Can these ultimately have the kinds of effects that we're looking for in humans?
And then, of course, we have the work that both Dennis and Bart talked about in considerable detail, which is, of course, we know neutralizing antibodies will do it, but then how do you elicit these broadly neutralizing antibodies [00:25:00] and what are the complex immunizing pathways that are going to be needed in order to do this?
I would argue that in the last 25 years, we've obviously witnessed considerable progress here. We know a lot about the immune responses against the virus, both the antibody responses, the cellular immune responses. But my second statement there is that we don't yet know whether we're really close to actually having what I call an epidemiologically-effective vaccine, or whether, for that matter, we can actually arrive at the goal. All right. We're hoping to be at the edge of the [00:25:30] precipice where we're there, but we don't know how close we are to the edge.
Very rapidly, there are a number of still open questions. I'm not going to go through these. These are all pretty obvious from all of the studies that we mentioned. But the one point I do want to make is that in the end, the answers are going to require human clinical studies. I think there's only so much as you can learn from preclinical models. In the end, you got to do the human clinical studies. These are not cheap clinical studies. They're going to require a large infrastructure, which logically exists, but it's going to require considerable funding a lot of time and a lot [00:26:00] long-term dedication to get there. The only thing we need to be careful of is that the studies are designed in such a way that you can interpret a negative result, because the high likelihood is that the majority of these will lead to negative results, but you need to be able to interpret them. We don't want to wind up in a cycle where we keep doing study after study after study because we don't get what we're looking for. You certainly are not going to be able to do that with clinical studies given the expense.
So I often get asked the question, is it really worth doing this to such an extent and [00:26:30] moving forward into clinical studies, because—we're talking hundreds of millions of dollars to do all of this? Well, you heard me say over the last couple of days and comments from the audience that we're at the edge. We have to be careful here because we're at the edge of potentially losing control of the epidemic. These are UNAIDS data. This shows the incidence of new HIV infection, global incidents over the last half a decade. As you can see, it's flattened out. We have pretty much a flat incidence. In sub-populations, as you heard in [00:27:00] sub-Saharan Africa, these incidents numbers are very, very high. It's an interesting thing, so to speak.
If one takes a look a—This is, over here is the population of 15 to 24-year-olds in Sub-Saharan Africa. 15 to 24-year-olds is that age group where you're just beginning to enter into that age group where you're becoming susceptible to HIV infection and potentially susceptible to HIV infection. There is this demographic bulge, as it's called, of young people entering [00:27:30] into this age group. This reflects the positive benefits over the last 15 years of controlling infant mortality. A very large number of age groups. We're going to find ourselves in the almost ironic situation, and it's easy enough to model, where 15 years from now, we may, in fact, have a larger absolute number of HIV-infected individuals in sub-Saharan Africa than we actually had 15 years ago, simply because of this, if the incidence [00:28:00] remains flat, all right? In the absence of interventions, whether they be an effective vaccine, whether they be an effective long-term prophylactic agent, in the absence of those interventions, this is where we're going to wind up.
So continuing to do the work that we're doing collectively, both long-acting prophylactic agents and on vaccines is fundamentally critical. If the effort requires having to make the time and money, investment to do human studies, then we have to do them. [unintelligible 00:28:27]
I'm going to leave you with this [00:28:30] final quote which came from the News & Views article that was published by Jeff Lifson and Mal Martin. (22) It said, "As someone accustomed to persevering on a long-term project in which repeated periods of hard work lead to modest progress, only to be followed by setbacks, Sisyphus would be well suited to a career in AIDS-vaccine research." Now, this parable is usually taken as a parable of futility. I will tell you, both to myself and my colleagues, that in the end, [00:29:00] this allows Sisyphus actually to get himself out of bed every morning. In the end, in spite of all of this, Sisyphus did this because he hopes that one day, the boulder will stay on top of the hill, right? That's where, ultimately, we all need to go and you have to get up every day to do it. All right. Thanks, Dan, and thank you, everybody.
Dan Barouch (moderator): We'll take one, maybe two quick questions for Emilio.
Emilio: We have one right here.
David Gludish: [00:29:30] My question is a simple one. Just the second last slide with the youths living with HIV. I think it would be really informative for us to know how this shakes down in terms of kids who were actually born with HIV-positive mothers and how many of these are—
Emilio: The impact on mother-to-child transmission has been extraordinary because that's where a fair amount of that original drop in incidents that you saw [00:30:00] was, in fact, due to that, all right? That continues to be well. It's not perfect, but it really had a substantial impact. The incidents that we're seeing right now is largely incidents primarily due to sexual transmission, particularly in high-prevalence populations.
Dan: Any other questions for Emilio? All right. Well, thank you very much.
Emilio: Thank you, Dan. Thank you.
[00:30:27] [END OF AUDIO]
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- 2.4 Robert Gallo — Discoveries of Human Retrovirus, Their Linkage to Disease as Causative Agents & Preparation for the Future
- 3.3 Douglas Richman: Antiviral Drug Resistance and Combination ART
- 4.0.1 Jeffrey Lifson — Session 4, Introduction 1
- 6.2 Dennis Burton — How Does HIV Evade the Antibody Response?
- 6.3 Bruce Walker — Role of T Cells in Controlling HIV Infection
- 6.4 Barton Haynes — Development of HIV Vaccine: Steps and Missteps
- 8.2 David Ho — Unraveling of HIV Dynamics In Vivo
- 8.6 David Baltimore — Bringing it to an End (And Where Are We Going?)
- Africa, sub-Saharan Africa
- antiretroviral therapy (ART)
- Bethesda, Maryland
- Bill & Melinda Gates Foundation
- capsid, capsid protein (p24)
- cell culture, tissue culture, immortalized cell line
- chimpanzee (Pan troglodytes)
- clinical trials (phases of clinical research)
- control — experimental control, control group, blinded experiment
- credit, priority
- cohort study
- drug resistance
- education and early career
- EFV (efavirenz)
- funding and grants
- Gludish, David W.
- H9 (HuT 78) cell line
- highly active antiretroviral therapy (HAART), combination antiretroviral therapy (cART)
- Hilleman, Maurice (1919–2005)
- IAVI (International AIDS Vaccine Initiative)
- in vitro vs. in vivo
- indinavir (IDV, Crixivan)
- Koup, Richard A.
- lab safety, biosafety levels, safety protocol
- Letvin, Norman L. (1949–2012)
- lymphatic system (lymph, lymph nodes, etc.)
- Martin, Malcolm A.
- Merck & Co., Inc. (Merck Sharp & Dohme)
- models (model systems, model organisms, modeling)
- monoclonal antibody
- mother-to-child transmission of HIV
- National Cancer Institute (NCI)
- National Institutes of Health (NIH)
- Nature (journal)
- nevirapine (NVP, Viramune)
- New York
- New York Hospital–Cornell Medical Center
- non-nucleoside reverse-transcriptase inhibitors (NNRTIs)
- pharmaceutical industry
- Picker, Louis
- polio, polio vaccine
- RV 144 (2003–2009)
- Saag, Michael S. (b. 1955)
- scientific competition and collaboration
- Scolnick, Edward
- Session 6: Immunology and Prevention
- simian immunodeficiency virus (SIV)
- simian-human immunodeficiency virus (SHIV)
- specimen exchange
- STEP study (2004–2011)
- Stony Brook University, Renaissance School of Medicine
- structural biology
- University of Alabama at Birmingham (UAB)
- Vagelos, P. Roy (b. 1929)
- Venezuelan equine encephalitis virus (VEE)
- Wimmer, Eckard (b. 1936)
- Wyeth (1860–2009)
Found 13 search result(s) for Emini.
... 6.4 Barton Haynes — Development of HIV Vaccine: Steps and Missteps 6.5 Emilio Emini — Issues in HIV Vaccine Development: Will the Future be any Easier than the Past
Mar 06, 2021
... Barton Haynes — Development of HIV Vaccine: Steps and Missteps https://libwiki.cshl.edu/confluence/pages/viewpage.action?pageId=12943560&src=contextnavpagetreemode 6.5 Emilio Emini — Issues in HIV Vaccine Development: Will the Future be any Easier than the Past? https://libwiki.cshl.edu/confluence/pages/viewpage.action?pageId=12943562&src=contextnavpagetreemode ...
Apr 27, 2021
... used a different protease inhibitor. There was indinavir 00:21:00 done with Emilio Emini, who's in the audience. There was nelfinavir done with the company Agouron, which I'm sure it has ...
Apr 27, 2021
... mention that exactly in parallel with what we were doing, Jack Nunberg and Emilio A. Emini were looking at a nonnucleoside RT inhibitor at Merck & Co., Inc. (Merck Sharp ...
Apr 27, 2021
... support within a company that was going through several leaderships. I know Emilio Emini was there at the start to help you out and he's another visionary for whom I have ...
Apr 27, 2021
... transmitted founder virus and, by the way, when you have these early samples, as Emilio Emini was saying, there is a virus 00:14:30 envelope that does start these lineages off ...
Apr 27, 2021
... 2: Thank you so much for that wonderful talk. Harriet: Emilio. Emilio Emini: Sharon, I just want to put in a note of caution here because the challenges ...
Apr 27, 2021
... than it is against if it's therapy. Harriet: Okay. One quick question. Emilio Emini: Yes, one question. You mentioned earlier, Dennis, and we've talked about ...
Apr 27, 2021
... full of controversy and I don’t think anybody really has an answer to that. Emilio Emini , wasn’t very optimistic about future for vaccine. Albert Sabin, before he ...
Apr 27, 2021
... wanted to just contextualize why medical interventions are important. I think Emilio Emini started to show why it's important to scale up interventions. This slide just ...
Apr 27, 2021
... one and that was 00:13:30 efavirenz (EFV). It was complicated. I'm sure Emilio Emini remembers this, that Merck and Bristol Myers had a collaboration on efavirenz where the different companies ...
Apr 27, 2021
... Xiping, Sajal K. Ghosh, Maria E. Taylor, Victoria A. Johnson, Emilio A. Emini, Paul Deutsch, Jeffrey D. Lifson, et al. “Viral Dynamics in Human ...
Apr 27, 2021
... Xiping, Sajal K. Ghosh, Maria E. Taylor, Victoria A. Johnson, Emilio A. Emini, Paul Deutsch, Jeffrey D. Lifson, et al. “Viral Dynamics in Human ...
Apr 27, 2021
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