Aids researchers and advocates were devastated in 2007, when a much anticipated vaccine against HIV unexpectedly failed to protect anyone in a clinical trial of 3,000 people. Even worse, the experimental inoculation, developed with money from the Merck pharmaceutical company and the National Institute of Allergy and Infectious Diseases, actually increased the chances that some people would later acquire HIV. Millions of dollars and more than a decade of research had gone into creating the vaccine. Meanwhile, in that same 10-year period, 18 million people died of AIDS, and millions more were infected. The Merck vaccine failed in large part because investigators do not yet know how to create the perfect vaccine. Yes, a number of vaccines have been spectacularly successful. Think of polio and smallpox. In truth, though, luck played a big role in those successes. Based on limited knowledge of the immune system and of the biology of a pathogen, investigators made educated guesses at vaccine formulations that might work and then, perhaps after some tinkering, had the good fortune to be proved right when the vaccine protected people. But all too often lack of insight into the needed immune response leads to disappointment, with a vaccine candidate recognized as ineffective only after a large human trial has been performed. What if investigators had a way to develop and evaluate potential vaccines that was faster and more efficient? Ideally, the alternative method would include a clear understanding of the precise mixture of immunological responses that must occur if a vaccine is to induce a strong protective reaction. Which subset of immune cells needs to interact with one another, for instance, and in what ways? Which collection of genes must those cells activate or depress? Researchers could then assemble such information into a system-wide profile or signature of protective immunity. This pattern, in turn, could serve as a guide for determining exactly what a vaccine needs to do to prevent disease. Scientists could compare hundreds of possible formulas, choosing to pursue only the ones that give rise to an immunological profile that is close to ideal. Then they could work on improving those potential vaccine formulas in small, quick human trials until they finally develop a handful of candidates that generate biological signatures as near to optimal as possible. By trying to match the ideal signature in these small tests, they could learn in a remarkably short period whether a vaccine had a good chance of working. By the time the final experimental vaccine was tested in large clinical trials on people, it would be virtually guaranteed to succeed. Until recently, scientists did not have the tools or the expertise to come close to that vision. We needed interdisciplinary teams able, collectively, to understand immunology and microbial biology, as well as how to model complex biological systems and find useful patterns in vast amounts of data. And we needed technologies able to simultaneously and repeatedly measure changes in gene activity, protein levels, cellular behavior and other features of immune responses—not to mention the computers and software able to process all those data. Now, however, a number of investigators who work in a field called systems biology are assembling such teams and have taken the first steps toward developing tools that could greatly improve the way vaccines are designed. As a community, we are beginning to decipher in detail the immune responses needed to protect a person against HIV. Systems biology approaches are now being used to develop vaccines against AIDS, as well as tuberculosis, malaria and influenza. Test Case All vaccines, whether formulated in the classic way or based on systems biology research, contain bits and pieces of viruses, bacteria or parasites that trigger very specific immune responses. Sometimes these bits and pieces, which scientists call antigens, are part of a whole but weaker virus (as was the case 200 years ago, when Edward Jenner inoculated a young boy against smallpox with the pus from a milkmaid’s cowpox blister). Other times the antigens are part of a whole but completely inactivated form of an infectious agent (such as the Salk version of the polio vaccine), or the antigen particles serve as the vaccine all by themselves (as in the vaccines against diphtheria, pertussis and tetanus). Vaccines may also include adjuvants—substances that pump up immune activity more generally. When all goes well, the immune system responds to the antigens in a vaccine with a carefully orchestrated cascade of molecular and cellular events that enables the body to block future infection by any virus or bacterium bearing the same or similar antigens. The trick for vaccine developers is to find the right combination of antigenic material and adjuvants to afford the strongest protection. Despite having been developed in the conventional way, the vaccine against yellow fever, known as YF-17D, hit the nail on the head. It is one of the most effective vaccines ever produced. A single shot provides effective immunity within a week, and protection lasts at least 30 years. This success provided an opportunity to test some of the ideas and methods of systems biology and prompted a study to do just that—which was led by Bali Pulendran of Emory University, with help from Rafi Ahmed’s team, also at Emory, and from my group at the Institute for Systems Biology in Seattle (ISB). Because we knew the vaccine worked, we thought we should be able identify a detailed profile of the molecular and cellular changes that account for the success in vaccinated individuals. We did find such a signature and are building on the experience to try to figure out why HIV vaccines have not been able to evoke the immunity needed to prevent infection. We started our yellow fever experiment by vaccinating 25 healthy volunteers with YF-17D. Then we took blood samples from the subjects at several points: at the time of injection, as well as one, three, seven and 21 days later. Each blood sample was placed into an automated screening device to figure out which genes were being activated. Of course, genes do not directly make the proteins that a cell needs. First the gene’s DNA is transcribed into messenger RNA molecules, which in turn are used as templates for building proteins. By looking at the RNA levels, then, we could tell not only which genes were expressed (used to make protein) but also how active they were. As we expected, the YF-17D inoculation first activated the innate immune system, which is the older (from an evolutionary perspective) of the two branches of the body’s defenses. The innate immune system provides an immediate counterattack against all forms of pathogens. Innate immune cells internalize and kill most invading microorganisms. Even though the innate response often takes care of the external threat on its own, the innate immune system instructs the younger adaptive immune system to generate customized responses specifically tailored to the invading pathogen so that the next time the infection occurs, the damage is limited and can be contained more quickly. About 10 days after inoculation, the innate defenses of our volunteers stimulated the adaptive immune system to react with two sequential salvos. First it generated specialized proteins called antibodies against various parts of the yellow fever virus, and then it activated a group of immune cells called killer T cells that recognize and destroy infected cells in the body. Over the course of several analyses, we identified 65 genes that played key roles in the body’s response to the YF-17D vaccine. Closer analysis showed that one specific expression pattern involving those genes was particularly indicative of both powerful antibody and killer T cell activation. In other words, we had proved our point. We could measure in minute detail exactly which genes of the immune system are turned on or off during the course of a robust immune response to the yellow fever vaccine. Rafick-Pierre Sékaly of the Vaccine and Gene Therapy Institute–Florida independently found similar results, and the agreement between the studies was reassuring. What is especially gratifying about these results is that the signatures of protection, arising from local immune responses at the site of vaccination, can be measured in the bloodstream. In principle, the findings mean that one could develop a simple diagnostic test based on blood from a finger prick to see how well a vaccine is working. Very little advanced training or complex equipment would be needed to collect and analyze data in a field study of a future vaccine—an important point when you consider that HIV, malaria and TB often strike hardest in the poorest parts of the world. Tackling HIV/AIDS Having demonstrated that the systems biology approach could provide a detailed picture of a successful vaccine’s effect on the immune system, my colleagues and I joined together to tackle the problem of HIV. Our next best step would have been to compare several vaccine formulas against one another to see if any evoked an ideal immune response. But we did not—and still do not—really know what an ideal immune response to HIV looks like, so finding such a signature is one of our major goals at the moment. We are beginning by looking for clues in animals. Research has shown that monkeys can be infected with a simian immunodeficiency virus (SIV) that bears many similarities to HIV. This susceptibility is important because monkeys can be deliberately infected in studies, whereas it is unethical to do so to humans. In collaboration with Louis Picker of Oregon Health and Science University and Robert Seder of the National Institutes of Health, researchers at Seattle BioMed are now testing different SIV-based vaccines in monkeys to learn more about the immunological profile associated with a strong immune response to that virus. To date, we have identified several signatures of the early innate immune response that predict which vaccinated animals will have fewer viruses in their blood after they have been subsequently exposed to SIV. Those genes whose expression correlates with an increased ability to fight off the virus emerge as highly connected nodes in a network diagram of the immune response; the nodes represent individual genes, and the connections between them indicate that they influence one another’s activities [see box on next two pages]. Because monkeys and people share so many of the same genes, the profile of an optimal monkey response may give us an idea of what the human signature of a strong response to HIV would look like and might also be used to evaluate different vaccines for their ability to work in humans. Picker and Sékaly are pursuing a related question. They are applying systems-level approaches to learn why vaccines made of weakened versions of SIV are particularly good at protecting nonhuman primates against later infection. Unfortunately in the case of HIV, the use of even a weakened virus is far too dangerous. Over the course of time it could occasionally recombine with full-strength versions of the virus and give people the very illness against which it was meant to protect. (That is why the live form of the polio vaccine is no longer used routinely in the U.S.) Success could point the way to inducing a response akin to one provided by a weakened virus without having to take the risk of actually using it in a vaccine. Learning from Failure Scientists from various institutions have now demonstrated that a systems approach can work at multiple stages of vaccine development. We have generated the immune signature of a completely protective vaccine (YF-17D). We have developed immune profiles of successfully vaccinated monkeys. But there are a few more puzzles we hope to solve before trying to develop a new HIV vaccine. Among them: Can we explain exactly why the Merck vaccine failed in 2007—a failure that shocked the AIDS community and that doomed what had seemed like a very promising vaccine candidate? The Merck vaccine (named MRKAd5/HIV-1) was, of course, not the first against HIV to be tested. Previous clinical trials focused on triggering an effective antibody response that would wipe out all HIV particles before they could take hold in the body. Unfortunately, two of the three main strategies for generating such vaccines were unavailable. Using a weakened version of HIV was too dangerous, and completely inactivated HIV particles did not produce the right kinds of antibodies. That left using bits and pieces of HIV either by themselves or attached to other viruses (to pump up immune activity). Alas, even these types of vaccines have not, to date, produced an unequivocally effective antibody response. (The results of a vaccine trial in Thailand, published in 2009, suggested a modestly effective antibody response, but the benefits were not broad enough to protect everyone, and all researchers believe the vaccine needs to be improved.) The MRKAd5/HIV-1 project took a different tack. Instead of trying to elicit a robust antibody response, it aimed to activate the killer T cell response of the adaptive immune system. As in previous attempts, the Merck vaccine used specific HIV antigens complexed to a safer virus—in this case a type 5 adenovirus, dubbed Ad5—to avoid the problems associated with using a whole HIV particle. (Adenoviruses are a frequent cause of the common cold.) Immunologists understood that the effort—even if completely successful—would not prevent the virus from infecting cells; antibodies also have to be present to achieve that goal. But it would, at least, keep viral reproduction to a minimum, by killing those infected cells. In theory, the vaccine would allow anyone who was exposed to HIV to fight the virus to a standstill indefinitely. The approach was state of the art. The study would be the first large-scale test of a vaccine specifically designed to activate T cells to kill HIV-infected cells. Pilot studies in nonhuman primates strongly suggested that the vaccine would provide some level of protection in people. Surprisingly, the Merck vaccine did not work. Despite successfully inducing a T cell response that was precisely directed against HIV-infected cells in more than 75 percent of test subjects (a truly remarkable result), an interim analysis of the data showed that HIV infection rates and viral levels were no different between the vaccine and placebo groups. Even more astonishing, participants with antibodies to Ad5 (because of previous exposure to an unrelated adenovirus type 5 infection) who received the vaccine appeared to be more likely to become infected than those in the placebo group. We teamed up with Julie McElrath of the Fred Hutchinson Cancer Research Center in Seattle to analyze the Merck vaccine. Together we determined that exposure to the MRKAd5/HIV-1 vaccine turned on thousands of genes within the first 24 hours after inoculation. That response was consistent with an exceptionally high rate of T cell activation. We further learned that these genes included all the expected major players of the innate immune system. But when we looked at blood samples taken from study subjects who already had antibodies to Ad5 (the same group that exhibited higher HIV infection rates in the vaccine trial), we found that the ramping up of their innate immune system was severely weakened. Quite possibly that critical weakness—which was completely unanticipated—made those study participants more likely to become infected when they later had sex or shared needles with partners who were HIV-positive. We are currently conducting further studies to see if we can confirm this hypothesis and explain why the strong T cell response did not provide the subjects with any protection. Next Steps For now the systems approach seems best suited to testing experimental vaccines after they have already been formulated to see if they are likely to offer effective protection. Eventually, however, the goal is to design vaccines from beginning to end in such a way that we know in advance that they will trigger the desired immune responses. Scientists have already made significant progress—for example, in understanding how certain adjuvants affect the immune system. My team has examined the gene networks that are activated by a wide array of adjuvants, and it is clear that some of these adjuvants trigger genes that tend to stimulate T cell responses, whereas other networks are more likely to skew the response toward the production of antibodies. By combining very detailed knowledge about adjuvants with the precise molecular signature of an optimal immune response, it is quite possible we will be able to optimize the production of vaccines against particular pathogens. In any event, my colleagues and I believe that a systems approach offers the greatest hope for more deliberate and predictable vaccine design. Only by understanding the immune system better can we create effective vaccines for such scourges as AIDS, malaria and tuberculosis. The pathogens that have given rise to these epidemics have so far defeated our utmost efforts at developing vaccines the traditional way. We simply cannot allow another generation of tens of millions of people to be wiped out by these global plagues.
Printed as: Fast Track to Vaccines
The Merck vaccine failed in large part because investigators do not yet know how to create the perfect vaccine. Yes, a number of vaccines have been spectacularly successful. Think of polio and smallpox. In truth, though, luck played a big role in those successes. Based on limited knowledge of the immune system and of the biology of a pathogen, investigators made educated guesses at vaccine formulations that might work and then, perhaps after some tinkering, had the good fortune to be proved right when the vaccine protected people. But all too often lack of insight into the needed immune response leads to disappointment, with a vaccine candidate recognized as ineffective only after a large human trial has been performed.
What if investigators had a way to develop and evaluate potential vaccines that was faster and more efficient? Ideally, the alternative method would include a clear understanding of the precise mixture of immunological responses that must occur if a vaccine is to induce a strong protective reaction. Which subset of immune cells needs to interact with one another, for instance, and in what ways? Which collection of genes must those cells activate or depress? Researchers could then assemble such information into a system-wide profile or signature of protective immunity. This pattern, in turn, could serve as a guide for determining exactly what a vaccine needs to do to prevent disease. Scientists could compare hundreds of possible formulas, choosing to pursue only the ones that give rise to an immunological profile that is close to ideal. Then they could work on improving those potential vaccine formulas in small, quick human trials until they finally develop a handful of candidates that generate biological signatures as near to optimal as possible. By trying to match the ideal signature in these small tests, they could learn in a remarkably short period whether a vaccine had a good chance of working. By the time the final experimental vaccine was tested in large clinical trials on people, it would be virtually guaranteed to succeed.
Until recently, scientists did not have the tools or the expertise to come close to that vision. We needed interdisciplinary teams able, collectively, to understand immunology and microbial biology, as well as how to model complex biological systems and find useful patterns in vast amounts of data. And we needed technologies able to simultaneously and repeatedly measure changes in gene activity, protein levels, cellular behavior and other features of immune responses—not to mention the computers and software able to process all those data.
Now, however, a number of investigators who work in a field called systems biology are assembling such teams and have taken the first steps toward developing tools that could greatly improve the way vaccines are designed. As a community, we are beginning to decipher in detail the immune responses needed to protect a person against HIV. Systems biology approaches are now being used to develop vaccines against AIDS, as well as tuberculosis, malaria and influenza.
Test Case All vaccines, whether formulated in the classic way or based on systems biology research, contain bits and pieces of viruses, bacteria or parasites that trigger very specific immune responses. Sometimes these bits and pieces, which scientists call antigens, are part of a whole but weaker virus (as was the case 200 years ago, when Edward Jenner inoculated a young boy against smallpox with the pus from a milkmaid’s cowpox blister). Other times the antigens are part of a whole but completely inactivated form of an infectious agent (such as the Salk version of the polio vaccine), or the antigen particles serve as the vaccine all by themselves (as in the vaccines against diphtheria, pertussis and tetanus). Vaccines may also include adjuvants—substances that pump up immune activity more generally. When all goes well, the immune system responds to the antigens in a vaccine with a carefully orchestrated cascade of molecular and cellular events that enables the body to block future infection by any virus or bacterium bearing the same or similar antigens. The trick for vaccine developers is to find the right combination of antigenic material and adjuvants to afford the strongest protection.
Despite having been developed in the conventional way, the vaccine against yellow fever, known as YF-17D, hit the nail on the head. It is one of the most effective vaccines ever produced. A single shot provides effective immunity within a week, and protection lasts at least 30 years. This success provided an opportunity to test some of the ideas and methods of systems biology and prompted a study to do just that—which was led by Bali Pulendran of Emory University, with help from Rafi Ahmed’s team, also at Emory, and from my group at the Institute for Systems Biology in Seattle (ISB). Because we knew the vaccine worked, we thought we should be able identify a detailed profile of the molecular and cellular changes that account for the success in vaccinated individuals. We did find such a signature and are building on the experience to try to figure out why HIV vaccines have not been able to evoke the immunity needed to prevent infection.
We started our yellow fever experiment by vaccinating 25 healthy volunteers with YF-17D. Then we took blood samples from the subjects at several points: at the time of injection, as well as one, three, seven and 21 days later. Each blood sample was placed into an automated screening device to figure out which genes were being activated. Of course, genes do not directly make the proteins that a cell needs. First the gene’s DNA is transcribed into messenger RNA molecules, which in turn are used as templates for building proteins. By looking at the RNA levels, then, we could tell not only which genes were expressed (used to make protein) but also how active they were.
As we expected, the YF-17D inoculation first activated the innate immune system, which is the older (from an evolutionary perspective) of the two branches of the body’s defenses. The innate immune system provides an immediate counterattack against all forms of pathogens. Innate immune cells internalize and kill most invading microorganisms. Even though the innate response often takes care of the external threat on its own, the innate immune system instructs the younger adaptive immune system to generate customized responses specifically tailored to the invading pathogen so that the next time the infection occurs, the damage is limited and can be contained more quickly.
About 10 days after inoculation, the innate defenses of our volunteers stimulated the adaptive immune system to react with two sequential salvos. First it generated specialized proteins called antibodies against various parts of the yellow fever virus, and then it activated a group of immune cells called killer T cells that recognize and destroy infected cells in the body. Over the course of several analyses, we identified 65 genes that played key roles in the body’s response to the YF-17D vaccine. Closer analysis showed that one specific expression pattern involving those genes was particularly indicative of both powerful antibody and killer T cell activation. In other words, we had proved our point. We could measure in minute detail exactly which genes of the immune system are turned on or off during the course of a robust immune response to the yellow fever vaccine. Rafick-Pierre Sékaly of the Vaccine and Gene Therapy Institute–Florida independently found similar results, and the agreement between the studies was reassuring.
What is especially gratifying about these results is that the signatures of protection, arising from local immune responses at the site of vaccination, can be measured in the bloodstream. In principle, the findings mean that one could develop a simple diagnostic test based on blood from a finger prick to see how well a vaccine is working. Very little advanced training or complex equipment would be needed to collect and analyze data in a field study of a future vaccine—an important point when you consider that HIV, malaria and TB often strike hardest in the poorest parts of the world.
Tackling HIV/AIDS Having demonstrated that the systems biology approach could provide a detailed picture of a successful vaccine’s effect on the immune system, my colleagues and I joined together to tackle the problem of HIV. Our next best step would have been to compare several vaccine formulas against one another to see if any evoked an ideal immune response. But we did not—and still do not—really know what an ideal immune response to HIV looks like, so finding such a signature is one of our major goals at the moment. We are beginning by looking for clues in animals.
Research has shown that monkeys can be infected with a simian immunodeficiency virus (SIV) that bears many similarities to HIV. This susceptibility is important because monkeys can be deliberately infected in studies, whereas it is unethical to do so to humans.
In collaboration with Louis Picker of Oregon Health and Science University and Robert Seder of the National Institutes of Health, researchers at Seattle BioMed are now testing different SIV-based vaccines in monkeys to learn more about the immunological profile associated with a strong immune response to that virus. To date, we have identified several signatures of the early innate immune response that predict which vaccinated animals will have fewer viruses in their blood after they have been subsequently exposed to SIV.
Those genes whose expression correlates with an increased ability to fight off the virus emerge as highly connected nodes in a network diagram of the immune response; the nodes represent individual genes, and the connections between them indicate that they influence one another’s activities [see box on next two pages]. Because monkeys and people share so many of the same genes, the profile of an optimal monkey response may give us an idea of what the human signature of a strong response to HIV would look like and might also be used to evaluate different vaccines for their ability to work in humans.
Picker and Sékaly are pursuing a related question. They are applying systems-level approaches to learn why vaccines made of weakened versions of SIV are particularly good at protecting nonhuman primates against later infection. Unfortunately in the case of HIV, the use of even a weakened virus is far too dangerous. Over the course of time it could occasionally recombine with full-strength versions of the virus and give people the very illness against which it was meant to protect. (That is why the live form of the polio vaccine is no longer used routinely in the U.S.) Success could point the way to inducing a response akin to one provided by a weakened virus without having to take the risk of actually using it in a vaccine.
Learning from Failure Scientists from various institutions have now demonstrated that a systems approach can work at multiple stages of vaccine development. We have generated the immune signature of a completely protective vaccine (YF-17D). We have developed immune profiles of successfully vaccinated monkeys. But there are a few more puzzles we hope to solve before trying to develop a new HIV vaccine. Among them: Can we explain exactly why the Merck vaccine failed in 2007—a failure that shocked the AIDS community and that doomed what had seemed like a very promising vaccine candidate?
The Merck vaccine (named MRKAd5/HIV-1) was, of course, not the first against HIV to be tested. Previous clinical trials focused on triggering an effective antibody response that would wipe out all HIV particles before they could take hold in the body. Unfortunately, two of the three main strategies for generating such vaccines were unavailable. Using a weakened version of HIV was too dangerous, and completely inactivated HIV particles did not produce the right kinds of antibodies. That left using bits and pieces of HIV either by themselves or attached to other viruses (to pump up immune activity). Alas, even these types of vaccines have not, to date, produced an unequivocally effective antibody response. (The results of a vaccine trial in Thailand, published in 2009, suggested a modestly effective antibody response, but the benefits were not broad enough to protect everyone, and all researchers believe the vaccine needs to be improved.)
The MRKAd5/HIV-1 project took a different tack. Instead of trying to elicit a robust antibody response, it aimed to activate the killer T cell response of the adaptive immune system. As in previous attempts, the Merck vaccine used specific HIV antigens complexed to a safer virus—in this case a type 5 adenovirus, dubbed Ad5—to avoid the problems associated with using a whole HIV particle. (Adenoviruses are a frequent cause of the common cold.) Immunologists understood that the effort—even if completely successful—would not prevent the virus from infecting cells; antibodies also have to be present to achieve that goal. But it would, at least, keep viral reproduction to a minimum, by killing those infected cells. In theory, the vaccine would allow anyone who was exposed to HIV to fight the virus to a standstill indefinitely.
The approach was state of the art. The study would be the first large-scale test of a vaccine specifically designed to activate T cells to kill HIV-infected cells. Pilot studies in nonhuman primates strongly suggested that the vaccine would provide some level of protection in people.
Surprisingly, the Merck vaccine did not work. Despite successfully inducing a T cell response that was precisely directed against HIV-infected cells in more than 75 percent of test subjects (a truly remarkable result), an interim analysis of the data showed that HIV infection rates and viral levels were no different between the vaccine and placebo groups. Even more astonishing, participants with antibodies to Ad5 (because of previous exposure to an unrelated adenovirus type 5 infection) who received the vaccine appeared to be more likely to become infected than those in the placebo group.
We teamed up with Julie McElrath of the Fred Hutchinson Cancer Research Center in Seattle to analyze the Merck vaccine. Together we determined that exposure to the MRKAd5/HIV-1 vaccine turned on thousands of genes within the first 24 hours after inoculation. That response was consistent with an exceptionally high rate of T cell activation. We further learned that these genes included all the expected major players of the innate immune system. But when we looked at blood samples taken from study subjects who already had antibodies to Ad5 (the same group that exhibited higher HIV infection rates in the vaccine trial), we found that the ramping up of their innate immune system was severely weakened.
Quite possibly that critical weakness—which was completely unanticipated—made those study participants more likely to become infected when they later had sex or shared needles with partners who were HIV-positive. We are currently conducting further studies to see if we can confirm this hypothesis and explain why the strong T cell response did not provide the subjects with any protection.
Next Steps For now the systems approach seems best suited to testing experimental vaccines after they have already been formulated to see if they are likely to offer effective protection. Eventually, however, the goal is to design vaccines from beginning to end in such a way that we know in advance that they will trigger the desired immune responses.
Scientists have already made significant progress—for example, in understanding how certain adjuvants affect the immune system. My team has examined the gene networks that are activated by a wide array of adjuvants, and it is clear that some of these adjuvants trigger genes that tend to stimulate T cell responses, whereas other networks are more likely to skew the response toward the production of antibodies. By combining very detailed knowledge about adjuvants with the precise molecular signature of an optimal immune response, it is quite possible we will be able to optimize the production of vaccines against particular pathogens.
In any event, my colleagues and I believe that a systems approach offers the greatest hope for more deliberate and predictable vaccine design. Only by understanding the immune system better can we create effective vaccines for such scourges as AIDS, malaria and tuberculosis. The pathogens that have given rise to these epidemics have so far defeated our utmost efforts at developing vaccines the traditional way. We simply cannot allow another generation of tens of millions of people to be wiped out by these global plagues.
Printed as: Fast Track to Vaccines
