Coxiella burnetii is the etiological agent of Q fever, a disease that is often spread to humans via inhalational exposure to the bacteria from contaminated agricultural sources. Outbreaks have been ...observed all over the world with larger foci generating interest in vaccination programs, most notably in Australia and the Netherlands. Importantly, exposure rates among military personnel deployed to the Middle East can be relatively high as measured by seroconversion to C. burnetii-specific antibodies. Q fever has been of interest to the biodefense community over the years due to its low infectious dose and environmental stability. Recent advances in cell-free growth and genetics of C. burnetii also make this organism easier to culture and manipulate. While there is a vaccine that is licensed for use in Australia, the combination of biodefense- and public health-related issues associated with Q fever warrant the development of a safer and more effective vaccine against this disease.
The Biomedical Advanced Research and Development Authority, part of the Administration for Strategic Preparedness and Response within the U.S. Department of Health and Human Services, recognizes that ...the evaluation of medical countermeasures under the Animal Rule requires well-characterized and reproducible animal models that are likely to be predictive of clinical benefit. Marburg virus (MARV), one of two members of the genus Marburgvirus, is characterized by a hemorrhagic fever and a high case fatality rate for which there are no licensed vaccines or therapeutics available. This natural history study consisted of twelve cynomolgus macaques challenged with 1000 PFU of MARV Angola and observed for body weight, temperature, viremia, hematology, clinical chemistry, and coagulation at multiple time points. All animals succumbed to disease within 8 days and exhibited signs consistent with those observed in human cases, including viremia, fever, systemic inflammation, coagulopathy, and lymphocytolysis, among others. Additionally, this study determined the time from exposure to onset of disease manifestations and the time course, frequency, and magnitude of the manifestations. This study will be instrumental in the design and development of medical countermeasures to Marburg virus disease.
The 2014-2016 Ebola virus epidemic in West Africa triggered extensive investments from public and private partners in an attempt to slow the spread of disease and bring the outbreak under control. ...This significantly accelerated the pace of development of countermeasures against Zaire ebolavirus that enabled vaccines to be a part of an effective response to the most recent 2018-2019 outbreak in the Democratic Republic of the Congo. However, there remain urgent and unmet needs for medical countermeasures against other members of the Filoviridae family that cause viral hemorrhagic fevers. To improve the national and global preparedness posture for viral hemorrhagic fevers, a renewed emphasis is being placed on developing vaccines for filoviruses other than Zaire ebolavirus. Here we discuss lessons learned from the West Africa epidemic and how those lessons apply to the development of vaccine candidates for other filoviruses, specifically Sudan ebolavirus and Marburg virus. This commentary will highlight some of the key product development gaps to address in preparation for future disease outbreaks caused by these viruses.
As the global response to COVID-19 continues, government stakeholders and private partners must keep an eye on the future for the next emerging viral threat with pandemic potential. Many of the virus ...families considered to be among these threats currently cause sporadic outbreaks of unpredictable size and timing. This represents a major challenge in terms of both obtaining sufficient funding to develop vaccines, and the ability to evaluate clinical efficacy in the field. However, this also presents an opportunity in which vaccines, along with robust diagnostics and contact tracing, can be utilized to respond to outbreaks as they occur, and limit the potential for further spread of the disease in question. While mRNA-based vaccines have proven, during the COVID-19 response, to be an effective and safe solution in terms of providing a rapid response to vaccine development, virus vector-based vaccines represent a class of vaccines that can offer key advantages in certain performance characteristics with regard to viruses of pandemic potential. Here, we will discuss some of the key pros and cons of viral vector vaccines in the context of preparing for future pandemics.
On November 7th and 8th, 2022, The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), The Coalition for Epidemic Preparedness Innovation ...(CEPI), The Bill & Melinda Gates Foundation (BMGF), The Biomedical Advanced Research and Development Authority (BARDA), and the Wellcome Trust hosted a virtual workshop entitled “Mucosal Vaccines for SARS-CoV-2: Scientific Gaps and Opportunities.” During the workshop, researchers and vaccine developers from around the world discussed the potential of mucosal vaccines to block SARS-CoV-2 transmission and reviewed the status of SARS-CoV-2 mucosal vaccine research. Here, we summarize key challenges and opportunities in basic, translational, and clinical research that were highlighted during the meeting. We also provide recommendations to advance the field and accelerate the development of mucosal vaccines for SARS-CoV-2.
A licensed anthrax vaccine has been available for pre-exposure prophylaxis in the United States since 1970, and it was approved for use as a post-exposure prophylaxis, in combination with antibiotic ...treatment, in 2015. A variety of other vaccines are available in other nations, approved under various regulatory frameworks. However, investments in anthrax vaccines continue due to the severity of the threat posed by this bacterium, as both a naturally occurring pathogen and the potential for use as a bioweapon. In this review, we will capture the current landscape of anthrax vaccine development, focusing on those lead candidates in clinical development. Although approved products are available, a robust pipeline of candidate vaccines are still in development to try to address some of the key research gaps in the anthrax vaccine field. We will then highlight some of the most pressing needs in terms of anthrax vaccine research.
Abstract In response to the coronavirus disease 2019 (COVID-19) pandemic, vaccines were quickly and successfully developed and deployed, saving millions of lives globally. While first-generation ...vaccines are safe and effective in preventing disease caused by SARS-CoV-2, next-generation vaccines have the potential to improve efficacy and safety. Vaccines delivered by a mucosal route may elicit greater protective immunity at respiratory surfaces, thereby reducing transmission. Inclusion of viral antigens in addition to the spike protein may enhance protection against emerging variants of concern. Next-generation vaccine platforms with a new mechanism of action may necessitate efficacy trials to fulfill regulatory requirements. The Biomedical Advanced Research and Development Authority (BARDA) will be supporting Phase 2b clinical trials of candidate next-generation vaccines. The primary endpoint will be improved efficacy in terms of symptomatic disease relative to a currently approved COVID-19 vaccine. In this paper, we discuss the planned endpoints and potential challenges to this complex program.
Outbreaks of viral hemorrhagic fever caused by filoviruses have become more prevalent in recent years, with outbreaks of Ebola virus (EBOV), Sudan virus (SUDV), and Marburg virus (MARV) all occurring ...in 2022 and 2023. While licensed vaccines are now available for EBOV, vaccine candidates for SUDV and MARV are all in preclinical or early clinical development phases. During the recent outbreak of SUDV virus disease, the Biomedical Advanced Research and Development Authority (BARDA), as part of the Administration for Strategic Preparedness and Response within the U.S. Department of Health and Human Services, implemented key actions with our existing partners to advance preparedness and enable rapid response to the outbreak, while also aligning with global partners involved in the implementation of clinical trials in an outbreak setting. Beyond pre-existing plans prior to the outbreak, BARDA worked with product sponsors to expedite manufacturing of vaccine doses that could be utilized in clinical trials. While the SUDV outbreak has since ended, a new outbreak of MARV disease has emerged. It remains critical that we continue to advance a portfolio of vaccines against SUDV and MARV while also expediting manufacturing activities ahead of, or in parallel if needed, outbreaks.
•Biomedical Advanced Research and Development Authority vaccine program.•Ebola outbreak response.•Ebola vaccine development.
The Ebola virus epidemic in West Africa proved to be the largest in the ...history of filovirus outbreaks, causing the World Health Organization to declare a public health emergency of international concern in August of 2014. In collaboration with domestic and international partners, the Biomedical Advanced Research and Development Authority (BARDA) initiated several vaccine development projects in support of the overall response efforts. The urgency associated with the epidemic triggered the clinical evaluation of lead vaccine candidates starting in late 2014. Here we will discuss development of the lead vaccine candidates for Ebola virus, specifically Zaire ebolavirus.
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