Highlights • Emerging Infectious Diseases require novel approaches to vaccine development. • EID vaccine development typically occurs within a knowledge vacuum. • Vaccine design may occur with few ...studies of disease epidemiology and pathogenesis. • Vaccine development for EIDs is benefitted by a platform technology. • EID trial design must be fluid and adapt to real-time alterations in epidemiology. • Societal and cultural norms and ethical concerns require input from key stakeholders.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
The past decade and a half has been characterized by numerous emerging infectious diseases. With each new threat, there has been a call for rapid vaccine development. Pathogens such as the Middle ...East Respiratory Syndrome coronavirus (MERS-CoV) and the Zika virus represent either new viral entities or viruses emergent in new geographic locales and characterized by novel complications. Both serve as paradigms for the global spread that can accompany new pathogens. In this paper, we review the epidemiology and pathogenesis of MERS-CoV and Zika virus with respect to vaccine development. The challenges in vaccine development and the approach to clinical trial design to test vaccine candidates for disease entities with a changing epidemiology are discussed.
Zika virus is an emergent pathogen that gained significant importance during the epidemic in South and Central America as unusual and alarming complications of infection were recognized. Although ...initially considered a self-limited benign infection, a panoply of neurologic complications were recognized including a Guillain-Barre-like syndrome and in-utero fetal infection causing microcephaly, blindness, and other congenital neurologic complications. Numerous Zika virus vaccines were developed, with nine different vaccines representing five different platforms entered into clinical trials, one progressing to Phase II. Here we review the current landscape and challenges confronting Zika virus vaccine development.
Emerging and emergent infectious diseases (EIDs) represent a significant and growing cause of morbidity and mortality with increased potential for pandemics due to globalization and international ...trade. Challenges remain to the approach toward vaccine development for EIDs. This Special Feature explores areas related to vaccine development and testing, including unique challenges posed in the developing world. Vaccines against multiple pathogens spanning a number of viral families are explored with respect to past activities through to future commercialization. Cost drivers balanced against clinical need are discussed and unique challenges posed by rare diseases are considered.
Electrospray deposition (ESD) is a promising technique for depositing micro-/nano-scale droplets and particles with high quality and repeatability. It is particularly attractive for surface coating ...of costly and delicate biomaterials and bioactive compounds. While high efficiency of ESD has only been successfully demonstrated for spraying surfaces larger than the spray plume, this work extends its utility to smaller surfaces. It is shown that by architecting the local "charge landscape", ESD coatings of surfaces smaller than plume size can be achieved. Efficiency approaching 100% is demonstrated with multiple model materials, including biocompatible polymers, proteins, and bioactive small molecules, on both flat and microneedle array targets. UV-visible spectroscopy and high-performance liquid chromatography measurements validate the high efficiency and quality of the sprayed material. Here, we show how this process is an efficient and more competitive alternative to other conformal coating mechanisms, such as dip coating or inkjet printing, for micro-engineered applications.
There are no known specific therapies or vaccines to treat or prevent Zika virus infection. In this report, encouraging data are presented from a phase 1 study of a DNA vaccine against ZIKV infection.
Although the incidence of severe fever with thrombocytopenia syndrome virus (SFTSV) infection has increased from its discovery with a mortality rate of 10-20%, no effective vaccines are currently ...available. Here we describe the development of a SFTSV DNA vaccine, its immunogenicity, and its protective efficacy. Vaccine candidates induce both a neutralizing antibody response and multifunctional SFTSV-specific T cell response in mice and ferrets. When the vaccine efficacy is investigated in aged-ferrets that recapitulate fatal clinical symptoms, vaccinated ferrets are completely protected from lethal SFTSV challenge without developing any clinical signs. A serum transfer study reveals that anti-envelope antibodies play an important role in protective immunity. Our results suggest that Gn/Gc may be the most effective antigens for inducing protective immunity and non-envelope-specific T cell responses also can contribute to protection against SFTSV infection. This study provides important insights into the development of an effective vaccine, as well as corresponding immune parameters, to control SFTSV infection.
Nonlive vaccine approaches that are simple to deliver and stable at room temperature or 2-8°C could be advantageous in controlling future Ebola virus (EBOV) outbreaks. Using an immunopotent DNA ...vaccine that generates protection from lethal EBOV challenge in small animals and nonhuman primates, we performed a clinical study to evaluate both intramuscular (IM) and novel intradermal (ID) DNA delivery.
Two DNA vaccine candidates (INO-4201 and INO-4202) targeting the EBOV glycoprotein (GP) were evaluated for safety, tolerability, and immunogenicity in a phase 1 clinical trial. The candidates were evaluated alone, together, or in combination with plasmid-encoded human cytokine interleukin-12 followed by in vivo electroporation using either the CELLECTRA® IM or ID delivery devices.
The safety profile of all 5 regimens was shown to be benign, with the ID route being better tolerated. Antibodies to EBOV GP were generated by all 5 regimens with the fastest and steepest rise observed in the ID group. Cellular immune responses were generated with every regimen.
ID delivery of INO-4201 was well tolerated and resulted in 100% seroreactivity after 2 doses and elicited interferon-γ T-cell responses in over 70% of subjects, providing a new approach for EBOV prevention in diverse populations. Clinical Trials Registration. NCT02464670.
From its discovery in Uganda in 1947, Zika virus (ZIKV) was considered a relatively innocuous viral pathogen with sporadic and infrequent occurrence of human infection. It was during an outbreak in ...French Polynesia in 2014 when cases of Guillain-Barré syndrome were identified as a serious complication of ZIKV infection in adults. However, in 2015, ZIKV emerged into and swept through South and Central America infecting millions of people. As part of the latter ZIKV outbreak, in Brazil, cases of microcephaly and other serious congenital complications affecting a large fraction of infants born to mothers infected during pregnancy were first identified and linked to ZIKV. This chapter reviews the history and clinical manifestations of ZIKV infection and mechanisms of immunoprotection. It is notable that, while limited, historical monographs identified most, if not all, of the precepts that are considered as newly discovered.
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