News Article | May 11, 2017
HANOVER, NH - Investigators at Dartmouth's Geisel School of Medicine announced that two new studies of DAR-901, their investigational vaccine against tuberculosis (TB), have moved it to the forefront of new vaccines in development for global control of this deadly infectious disease. "We are very pleased with the results of these two studies" said Ford von Reyn, MD, professor of medicine at Geisel and principal investigator for the DAR-901 booster vaccine. "They represent major milestones on the path to approval of DAR?901 and the global fight against tuberculosis." Tuberculosis is the leading infectious disease cause of death in the world and there is a global effort to eradicate it by 2035. According to modeling by the World Health Organization a new vaccine will be required to meet this ambitious elimination goal. The Dartmouth candidate, DAR-901, is an inactivated vaccine made from a non-pathogenic bacterium that is genetically related to Mycobacterium tuberculosis, the cause of human tuberculosis. An earlier form of the vaccine was used in the DarDar Trial, a seven-year study in Tanzania sponsored by the U.S. National Institutes of Health involving patients with HIV infection who at birth had received BCG, the current tuberculosis vaccine. In that trial, the inactivated vaccine was effective as a booster in preventing tuberculosis. The DarDar Trial remains the only trial in which a new tuberculosis vaccine has shown efficacy in humans. Dartmouth and Aeras subsequently collaborated to develop an improved and scalable method for manufacturing the vaccine, now designated DAR-901. The two new studies on DAR-901 conducted in collaboration with Aeras were published in the journal PLOS ONE. In the pre-clinical study, BCG was administered first followed by a booster immunization with either DAR-901 or a second dose of BCG. Protection against subsequent tuberculosis challenge was greater with the DAR-901 booster than with the BCG booster. In the clinical study, being published today, DAR-901 was administered to adults living in the United States who had received BCG at birth. A three-dose series of the vaccine was safe and well-tolerated. In addition, DAR-901 induced immune responses that were similar to those seen with the vaccine shown effective in the DarDar Trial. "Taken together, these two studies suggest that the new scalable vaccine formulation is likely to prove as effective as the original formulation - which would make it the first protective TB vaccine in humans since BCG, which was introduced almost a century ago," said Professor Ajit Lalvani, Director of the Tuberculosis Research Centre, National Heart and Lung Institute, Imperial College London and a member of the DAR-901 development team. Based on the study published today, a larger randomized trial is underway in Tanzania to determine if DAR-901 prevents the earliest stage of infection with tuberculosis, before symptoms are apparent. In February, the 650 adolescents in this "prevention of infection" study completed receiving 3 doses of DAR-901 or placebo. The vaccine was again observed to be safe and well-tolerated. The trial is sponsored by Global Health Innovative Technology Fund (Japan) and results of vaccine efficacy will be available in late 2018. Additional collaborators on the DAR-901 development team include Timothy Lahey, MD, Lisa Adams, MD, and Richard Waddell ScD, at Geisel, Robert Arbeit, MD, at Tufts University School of Medicine, C. Robert Horsburgh, MD, at Boston University School of Public Health, and Kisali Pallangyo, MD, and Patricia Munseri, MD, at Muhimbili University of Health and Allied Sciences (MUHAS) in Dar es Salaam Tanzania. The team is now developing plans for a large, randomized, placebo-controlled Phase 3 trial to support regulatory approval of DAR-901. The study is targeted to begin within two years. To read the latest study at PLOS ONE: http://journals. (link live 5/11/17 at 2:00 PM Eastern Time) The studies were supported by Dartmouth College, Aeras (Rockville, MD) and the Jack and Dorothy Byrne Foundation. About the Geisel School of Medicine at Dartmouth Founded in 1797, the Geisel School of Medicine at Dartmouth strives to improve the lives of the communities it serves through excellence in learning, discovery, and healing. The Geisel School of Medicine is renowned for its leadership in medical education, health care policy and delivery science, biomedical research, global health, and in creating innovations that improve lives worldwide. As one of America's leading medical schools, Dartmouth's Geisel School of Medicine is committed to training new generations of diverse leaders who will help solve our most vexing challenges in health care.
News Article | May 8, 2017
The initial study will assess immune responses of 10 healthy adults (ages 40-80) to a licensed hepatitis B vaccine. It will feature one of the most comprehensive analyses of how people respond to vaccinations to learn why some individuals are protected from a single dose, while others are not. The study will expand to include several hundred people – from neonates to the elderly in middle and low-income countries. "Developing a better understanding of why some groups of people are protected from disease is a goal that simply must be achieved," said Co-Principal Investigator Tobias Kollmann, M.D., Ph.D., professor of pediatrics at the University of British Columbia (UBC) and an investigator at the Vaccine Evaluation Center in Vancouver, Canada. "The licensed hepatitis B vaccine, which only works in about 30 percent of people on the first shot, is an ideal model vaccine to study general principles of human immunological protection because it is one of the few vaccines for which we know how it protects." The study will take place at the at the Vaccine Evaluation Center, in Vancouver, Canada, and will be augmented by extensive immunological and bioinformatic analyses at the Project's San Diego Mesa Consortium, which includes the J. Craig Venter Institute, the La Jolla Institute, The Scripps Research Institute, and UC San Diego, with clinical coordination by the Vanderbilt Institute for Clinical and Translational Research. "With technological advances in biomedical, computational and engineering sciences, we have an unprecedented opportunity to decipher the immune system's components and core principles required to generate long-lasting immunity against disease, and usher in a new era of global health," added Stanley Plotkin, M.D., Chairman of the Human Vaccines Project's Board of Directors. About the Human Vaccines Project| The Human Vaccines Project is a nonprofit public-private partnership with a mission to decode the human immune system to accelerate the development of vaccines and immunotherapies against major infectious diseases and cancers. The Project brings together leading academic research centers, industrial partners, nonprofits and governments to address the primary scientific barriers to developing new vaccines and immunotherapies. Support and funding for the Project includes the Robert Wood Johnson Foundation, John D. and Catherine T. MacArthur Foundation, GSK, Illumina, MedImmune, Sanofi Pasteur, Crucell/Janssen, Regeneron, Pfizer, Moderna, Boehringer Ingelheim, Aeras, Vanderbilt University Medical Center, UC San Diego, The Scripps Research Institute, J. Craig Venter Institute and La Jolla Institute for Allergy and Immunology. To learn more, visit www.humanvaccinesproject.org. For media inquiries, please contact Kierstin Coatney, Kierstin@globalgatewayadvisors.com or +1-716-378-1602. To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/new-study-aims-to-explain-the-rules-of-how-the-immune-system-works-300453028.html
News Article | May 3, 2017
In his role at the alternative investments management firm Altamar, Fernandez is focused on the design, fundraising and management of Altamar's Credit Business and is a member of the Investment Committee of Alta Life Sciences, a life sciences venture fund with a Spanish and European focus launched in 2016. Fernandez has also worked as Managing Director at Credit Agricole Corporate and Investment Bank, and as a consultant for the World Bank as a securities and debt capital markets expert. Fernandez has also served on the Board of Directors of the European Investment Bank and as a Board Member of CESCE (Spain's export credit agency). Between 2010 and 2013, he worked for Professor Andrew W. Lo at MIT's Laboratory for Financial Engineering on the biomedical megafund project. He has authored various papers on this field, focusing on the use of securitization techniques to spur investments in early stage drug development for critical diseases. Fernandez holds an MBA from MIT Sloan (Sloan Fellows Program in Innovation and Global Leadership), a Masters in Finance from the London Business School, a Masters in Portfolio Management degree from I.E.B. and Bachelor's Degree in Economics and Business from CUNEF (Madrid). "I have a passion for using financial engineering to solve problems and create a better, more sustainable world, and I believe that my goals and dreams align well with the mission of the Human Vaccines Project," said Fernandez. "I am eager to start my work in support of the Human Vaccines Project as the organization advances research in an area that is critical to the future of human health – decoding the human immune system to understand why and how it works to help the body combat diseases." About the Human Vaccines Project The Human Vaccines Project is a nonprofit public-private partnership with a mission to decode the human immune system to accelerate the development of vaccines and immunotherapies against major infectious diseases and cancers. The Project brings together leading academic research centers, industrial partners, nonprofits and governments to address the primary scientific barriers to developing new vaccines and immunotherapies. Support and funding for the Project includes the Robert Wood Johnson Foundation, John D. and Catherine T. MacArthur Foundation, GSK, MedImmune, Sanofi Pasteur, Crucell/Janssen, Regeneron, Pfizer, Moderna, Boehringer Ingelheim, Aeras, Vanderbilt University Medical Center, UC San Diego, The Scripps Research Institute, J. Craig Venter Institute and La Jolla Institute for Allergy and Immunology. To learn more, visit www.humanvaccinesproject.org. To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/jose-maria-fernandez-joins-the-human-vaccines-project-board-of-directors-300450282.html
Tameris M.D.,University of Cape Town |
Hatherill M.,University of Cape Town |
Landry B.S.,Aeras |
Scriba T.J.,University of Cape Town |
And 9 more authors.
The Lancet | Year: 2013
Background BCG vaccination provides incomplete protection against tuberculosis in infants. A new vaccine, modified Vaccinia Ankara virus expressing antigen 85A (MVA85A), was designed to enhance the protective efficacy of BCG. We aimed to assess safety, immunogenicity, and efficacy of MVA85A against tuberculosis and Mycobacterium tuberculosis infection in infants. Methods In our double-blind, randomised, placebo-controlled phase 2b trial, we enrolled healthy infants (aged 4-6 months) without HIV infection who had previously received BCG vaccination. We randomly allocated infants (1:1), according to an independently generated sequence with block sizes of four, to receive one intradermal dose of MVA85A or an equal volume of Candida skin test antigen as placebo at a clinical facility in a rural region near Cape Town, South Africa. We actively followed up infants every 3 months for up to 37 months. The primary study outcome was safety (incidence of adverse and serious adverse events) in all vaccinated participants, but we also assessed efficacy in a protocol-defined group of participants who received at least one dose of allocated vaccine. The primary efficacy endpoint was incident tuberculosis incorporating microbiological, radiological, and clinical criteria, and the secondary efficacy endpoint was M tuberculosis infection according to QuantiFERON TB Gold In-tube conversion (Cellestis, Australia). This trial was registered with the South African National Clinical Trials Register (DOH-27-0109-2654) and with ClinicalTrials.gov on July 31, 2009, number NCT00953927 Findings Between July 15, 2009, and May 4, 2011, we enrolled 2797 infants (1399 allocated MVA85A and 1398 allocated placebo). Median follow-up in the per-protocol population was 24•6 months (IQR 19•2-28•1), and did not differ between groups. More infants who received MVA85A than controls had at least one local adverse event (1251 [89%] of 1399 MVA85A recipients and 628 [45%] of 1396 controls who received the allocated intervention) but the numbers of infants with systemic adverse events (1120 [80%] and 1059 [76%]) or serious adverse events (257 [18%] and 258 (18%) did not differ between groups. None of the 648 serious adverse events in these 515 infants was related to MVA85A. 32 (2%) of 1399 MVA85A recipients met the primary efficacy endpoint (tuberculosis incidence of 1•15 per 100 person-years [95% CI 0•79 to 1•62]; with conversion in 178 [13%] of 1398 infants [95% CI 11•0 to 14•6]) as did 39 (3%) of 1395 controls (1•39 per 100 person-years [1•00 to 1•91]; with conversion in 171 [12%] of 1394 infants [10•6 to 14•1]). Efficacy against tuberculosis was 17•3% (95% CI -31•9 to 48•2) and against M tuberculosis infection was -3•8% (-28•1 to 15•9). Interpretation MVA85A was well tolerated and induced modest cell-mediated immune responses. Reasons for the absence of MVA85A efficacy against tuberculosis or M tuberculosis infection in infants need exploration. Funding Aeras, Wellcome Trust, and Oxford-Emergent Tuberculosis Consortium (OETC).
News Article | November 17, 2016
The Human Vaccines Project and Boehringer Ingelheim are pleased to announce a three-year collaboration agreement to support their mutual objective to decode the human immune system with the aim of accelerating understanding and development of immunotherapies overall as well as better vaccines for cancer treatment. Under the terms of the agreement, Boehringer Ingelheim’s contributions to the Project will help catalyze the Project’s expanding programs. “We are tremendously honored that Boehringer Ingelheim has elected to partner with the Project, joining a growing number of leading, global biopharmaceutical companies committed to addressing the key scientific challenges impeding development of next generation vaccines and immunotherapies,” said Wayne C. Koff, Ph.D., President and CEO of the Human Vaccines Project. “Boehringer Ingelheim brings exceptional basic science and clinical research expertise in the areas of oncology and human immunology, and is at the forefront of biopharma innovation in these areas.” A revolution is ongoing in cancer immunotherapy, due to the recent realization of the importance of “checkpoints,” proteins that enable tumors to evade the immune system’s ability to kill the tumor, and novel therapeutics termed “checkpoint inhibitors” that have provided dramatic clinical benefit in managing a subset of cancers in a limited number of patients. “Despite these exciting breakthroughs, our understanding of how the immune system can best be harnessed to attack and eliminate tumors remains limited. A better understanding of the human immune system in healthy individuals as well as patients, and how best to measure and direct the immune system is needed,” said Clive R. Wood, Ph.D., Senior Corporate Vice President, Discovery Research at Boehringer Ingelheim. “We are pleased to become a partner in this groundbreaking project which offers the potential to open a new era in vaccine and immunotherapeutic development. This complements our strong commitment to cancer immunology with a pipeline that includes among others, a therapeutic cancer vaccine and next generation checkpoint inhibitors.” Within the Human Vaccines Project’s scientific network, investigators at leading academic research centers are seeking to determine the central components of the human immune system at the molecular and structural level, as well as the common rules by which the immune system generates specific and durable protective responses against a range of infectious and neoplastic diseases. Successful achievement of these goals should enable accelerated development of new and improved vaccines and therapeutics for major global diseases. “The Human Vaccines Project is one of the more promising projects to help transform the future of vaccine development and cancer immunotherapy. JCVI is pleased to be adding our bioinformatics acumen as part of this effort to help conquer some of the most devastating diseases of the 21st century,” said J. Craig Venter, Founder, Chairman and CEO of the J. Craig Venter Institute which recently joined together with the Scripps Research Institute, La Jolla Institute and UC San Diego to serve as a scientific hub for the Project. About the Human Vaccines Project The Human Vaccines Project is a non-profit public-private partnership with the mission to accelerate the development of vaccines and immunotherapies against major infectious diseases and cancers by decoding the human immune system. The Project has a growing list of partners and financial supporters including: Vanderbilt University Medical Center, the J. Craig Venter Institute, the La Jolla Institute, The Scripps Research Institute, UC San Diego, Aeras, Crucell/Janssen, GSK, Pfizer, MedImmune, Regeneron, Sanofi Pasteur, the Robert Wood Johnson Foundation and the John D. and Catherine T. MacArthur Foundation. The Project brings together leading academic research centers, industrial partners, nonprofits and governments to address the primary scientific barriers to developing new vaccines and immunotherapies, and has been endorsed by 35 of the world’s leading vaccine scientists.
News Article | April 12, 2016
A team of scientists led by Oxford University have made a discovery that could improve our chances of developing an effective vaccine against Tuberculosis. The researchers have identified new biomarkers for Tuberculosis (TB) which have shown for the first time why immunity from the widely used Bacillus Calmette-Guérin (BCG) vaccine is so variable. The biomarkers will also provide valuable clues to assess whether potential new vaccines could be effective. TB remains one of the world's major killer diseases, causing TB disease in 9.6 million people and 1.5 million deaths in 2014. The only available vaccine, Bacillus Calmette-Guérin (BCG), works well (estimated 50 percent effective) to prevent severe disease in children but is very variable (0 percent to 80 percent effective) in how well it protects against lung disease, particularly in countries where TB is most common. While BCG is one of the safest and most widely used vaccines worldwide, there is one key issue: It is currently very difficult to determine whether it will work or not. This also makes it really hard to determine if any new vaccines might work. For many vaccines, medics and scientists can use what are called immune correlates or biomarkers, typically in the blood, which can be measured to determine whether a vaccine has successfully induced immunity. Not only are these correlates useful in measuring the success of existing vaccination programmes, they are also invaluable in assessing whether potential new vaccines could be effective. With a pressing need for a TB vaccine that is more effective than BCG, a research team drawn from a number of groups at Oxford University, working with colleagues from the South African Tuberculosis Vaccine Initiative at the University of Cape Town and the London School of Hygiene & Tropical Medicine, set out to identify immune correlates that could facilitate TB vaccine development. The team, funded by the Wellcome Trust and Aeras, and led by Professor Helen McShane and Dr. Helen Fletcher, studied immune responses in infants in South Africa who were taking part in a TB vaccine trial. Professor McShane said: "We looked at a number of factors that could be used as immune correlates, to try and find biomarkers that will help us develop a better vaccine." The team carried out tests for twenty-two possible factors. One - levels of activated HLA-DR+CD4+ T-cells - was linked to higher TB disease risk. Meanwhile, BCG-specific Interferon-gamma secreting T-cells indicated lower TB risk, with higher levels of these cells directly linked to greater reduction of the risk of TB. Antibodies to a TB protein, Ag85A, were also identified as a possible correlate. Higher levels of Ag85A antibody were associated with lower TB risk. However, the team cautions that other environmental and disease factors could also cause Ag85A antibody levels to rise and so there may not be a direct link between the antibody and TB risk. Professor McShane said: "These are useful results which ideally would now be confirmed in further trials. They show that antigen-specific T cells are important in protection against TB, but that activated T cells increase the risk". Dr. Helen Fletcher from the London School of Hygiene & Tropical Medicine, said: "For the first time we have some evidence of how BCG might work, and also what could block it from working. Although there is still much work to do, these findings may bring us a step closer to developing a more effective vaccine for TB." Dr. Tom Scriba from the South African Tuberculosis Vaccine Initiative said: "TB is still a major international killer, and rates of TB disease in some areas of South Africa are among the highest in the world. These findings provide important clues about the type of immunity TB vaccines should elicit, and bring us closer to our vision, a world without TB." The team is continuing its work to develop a TB vaccine, aiming to protect more people from the disease. The paper was published in the jounral Nature Communications.
Delogu G.,Catholic University of the Sacred Heart |
Manganelli R.,University of Padua |
Clinical Microbiology and Infection | Year: 2014
A new and improved vaccine against tuberculosis (TB) would provide a powerful tool to conquer one of the most insidious infectious diseases of mankind. Protection afforded by bacillus Calmette-Guérin (BCG) has been shown to be limited and inconsistent, especially in adults that are known to transmit TB disease. In the last two decades, several new vaccines have been developed and tested with the aim to elicit robust and long-lived T-cell responses against Mycobacterium tuberculosis antigens. Although much progress has been made in the TB vaccine field, there is an urgent need to address critical research questions about TB immunity with a special focus on designing vaccines aimed at preventing infection and transmission of TB. Here, we discuss the rationale behind the current immunization strategies being implemented for TB vaccines and provide some suggestions for hypothesis driven research to encourage the development of novel TB vaccines. © 2013 The Authors Clinical Microbiology and Infection. © 2013 European Society of Clinical Microbiology and Infectious Diseases.
News Article | November 7, 2016
BEIJING and LA JOLLA, Calif., Nov 7, 2016 /PRNewswire/ -- Yisheng Biopharma Co., Ltd. ("Yisheng Biopharma"), a biopharmaceutical company focusing on research, development, manufacturing, sales and marketing of vaccine products, today announced that it has entered into a collaboration with The Scripps Research Institute ("TSRI") to test a new generation of AIDS vaccine based on novel gp140 trimers and self-assembling nanoparticles designed by TSRI scientists and Toll-Like Receptor 3 (TLR3) agonist adjuvant technology ("PIKA") developed by the company. The cooperative research partnership represents a new opportunity for both organizations to create more effective and safe vaccine products against HIV infection. Under the terms of the agreement, the scientists at TSRI will evaluate the potential of PIKA adjuvant for AIDS vaccine candidates. The PIKA adjuvant is a proprietary technology developed by Yisheng Biopharma, named as part of "National Key Medicine Innovation" in 2013 by the National Ministry of Science and Technology of China. Most recently Yisheng completed Phase II and Phase I clinical studies of PIKA based rabies and hepatitis B vaccines, respectively, which exhibited promising efficacy and safety in human subjects. "TSRI has gained a great deal of expertise in AIDS research which lays the groundwork in revolutionizing vaccine design strategy," commented Assistant Professor Jiang Zhu at TSRI. "TLR-3 agonists such as PIKA adjuvant are known to enhance immune responses. When used together with highly optimized HIV vaccine immunogens, PIKA could activate innate immune signaling and induce a more robust immune response that confers protection against HIV infection. We look forward to working with researchers at Yisheng to develop a more powerful AIDS vaccine." "The partnership with TSRI is critical to our long-term vision in advancing vaccine development. We're thrilled to work alongside TSRI's world-class faculty and bring Yisheng's capabilities and focus to bear in creating new medicines into the future. We are very pleased to join forces with TSRI in exploring a more effective vaccine against AIDS, which remains a significant unmet medical need. Our PIKA adjuvant has exhibited broad potential in preclinical and clinical investigations against rabies, HIV, Hepatitis-B, influenza, tuberculosis, and other viruses, which could significantly change the clinical practice paradigms against many human and animal virus infections. We are looking forward to updating the progress on these fronts in due course," stated Mr. Yi Zhang, the Chairman of Yisheng Biopharma and the project leader of PIKA adjuvant technology. Mr. Zhang finally commented, "We are grateful to our research collaborators worldwide for their continuous support of PIKA adjuvant technology and vaccine development over the years, including The Pasteur Institute, the US NIH, the United States Army Medical Research Institute of Infectious Diseases, Chinese Center For Disease Control And Prevention (China CDC), China National Institutes For Food and Drug Control, DSO National Laboratories Singapore, Chinese Academy of Sciences, Australia QIMR, Sun Yat-Sen University of China, Aeras Pharmaceutical of the US, and Academy of Military Sciences of China." PIKA adjuvant technology is a proprietary technology developed in-house at Yisheng Biopharma. The adjuvant is a double- stranded RNA, which acts as a toll-like receptor-3 (TLR-3) ligand to the activation of the innate immune cells, such as dendritic cells, macrophages and NK cells. PIKA adjuvant is formulated as a component of vaccine candidates. The Scripps Research Institute (TSRI) is one of the world's largest independent, not-for-profit organizations focusing on research in the biomedical sciences. TSRI is internationally recognized for its contributions to science and health, including its role in laying the foundation for new treatments for cancer, rheumatoid arthritis, hemophilia, and other diseases. An institution that evolved from the Scripps Metabolic Clinic founded by philanthropist Ellen Browning Scripps in 1924, the institute now employs more than 2,500 people on its campuses in La Jolla, CA, and Jupiter, FL, where its renowned scientists - including two Nobel laureates and 20 members of the National Academy of Science, Engineering or Medicine - work toward their next discoveries. The institute's graduate program, which awards PhD degrees in biology and chemistry, ranks among the top ten of its kind in the nation. For more information, see www.scripps.edu. About Yisheng Biopharma Co., Ltd. Yisheng Biopharma Co., Ltd. is a biopharmaceutical company headquartered in Beijing, China, focusing on the research, development, manufacturing and sales and marketing of immunological and vaccine products, with approximately 1,000 employees in China, the USA and Singapore. For more information, see www.yishengbio.com
Hokey D.A.,Aeras |
Human Vaccines and Immunotherapeutics | Year: 2013
Tuberculosis continues to persist despite widespread use of BCG, the only licensed vaccine to prevent TB. BCG's limited efficacy coupled with the emergence of drug-resistant strains of Mycobacterium tuberculosis emphasizes the need for a more effective vaccine for combatting this disease. However, the development of a TB vaccine is hindered by the lack of immune correlates, suboptimal animal models, and limited funding. An adolescent/adult vaccine would have the greatest public health impact, but effective delivery of such a vaccine will require a better understanding of global TB epidemiology, improved infrastructure, and engagement of public health leaders and global manufacturers. Here we discuss the current state of tuberculosis vaccine research and development, including our understanding of the underlying immunology as well as the challenges and opportunities that may hinder or facilitate the development of a new and efficacious vaccine. © 2013 Landes Bioscience.
Graves A.J.,Aeras |
Human Vaccines and Immunotherapeutics | Year: 2015
A new tuberculosis vaccine is needed to replace or enhance BCG, which induces variable protection against Mycobacterium tuberculosis pulmonary infections in adults. Development of new TB vaccine candidates is severely hampered by the lack of a correlate of immunity, unproven animal models, and limited funding opportunities. One candidate, MVA85A, recently failed to meet its efficacy endpoint goals despite promising early-phase trial data. As a result, some in the field believe we should now shift our focus away from product development and toward a researchoriented approach. Here, we outline our suggestions for this research-oriented strategy including diversification of the candidate pipeline, expanding measurements of immunity, improving pre-clinical animal models, and investing in combination pre-clinical/experimental medicine studies. As with any evolution, this change in strategy comes at a cost but may also represent an opportunity for advancing the field. © AJ Graves and DA Hokey.