Results from a recent pre-clinical study reported this week in the online edition of the American Association of Pharmaceutical Scientists journal Molecular Pharmaceutics reveal that a potentially breathable, respiratory vaccine currently in accelerated development has been shown to provide long-term protection for non-human primates against the Ebola virus.
The study referred to represents the only proof to date that protection from a single dose of a non-injectable vaccine platform for Ebola is long-lasting, a finding that could have significant global implications in controlling future Ebola outbreaks. A breathable vaccine could help solve the logistical obstacles of storing, transporting and administering injectable vaccines in parts of Africa most afflicted by the virus.
The study, entitled “A Single Dose Respiratory Recombinant Adenovirus-Based Vaccine Provides Long-Term Protection for Non-Human Primates from Lethal Ebola Infection.” (Molecular Pharmaceutics, 2014; DOI: 10.1021/mp500646d ), coauthored by Jin Huk Choi , Kristina Jonsson-Schmunk , Xiangguo Qiu , Devon J Shedlock , Jim Strong , Jason X Xu , Kelly L Michie , Jonathan Audet , Lisa Fernando , Mark j Myers , David B. Weiner , Irnela Bajrovic , Lilian Q Tran , Gary Wong , Alexander Bello , Gary P Kobinger, Stephen C Schafer , and Maria A. Croyle, notes that as the current, worst-ever-in-history Ebola outbreak in West Africa continues and cases appear in the United States and other countries, the need for long-lasting vaccines to preserve global health is imminent.
The research team reports on their evaluation of the long-term efficacy of a respiratory and sublingual (SL) adenovirus-based vaccine in non-human primates in two phases.
In the first, a single respiratory dose of 1.4 10 9 infectious virus particles (ivp)/kg of Ad-CAGoptZGP induced strong Ebola-glycoprotein (GP) specific CD8+ and CD4+ T cell responses and Ebola GP-specific antibodies in systemic and mucosal compartments and was partially (67%) protective from challenge 62 days after immunization. The same dose given by the SL route induced Ebola GP-specific CD8+ T cell responses similar to those induced by intramuscular (IM) injection, however, the Ebola GP-specific antibody response was low.
The coauthors note that all primates succumbed to infection. Three primates were then given the vaccine in an IN formulation that improved the immune response to Ebola in rodents. Three primates were immunized with 2.0 1010 ivp/kg of vaccine by the SL route. Diverse populations of polyfunctional Ebola GP-specific CD4+ and CD8+ T cells and significant anti-Ebola GP antibodies were present in samples collected 150 days after respiratory immunization. The formulated vaccine was fully protective against challenge 21 weeks after immunization. While diverse populations of Ebola GP-specific CD4+ T cells were produced after SL immunization, antibodies were not neutralizing and the vaccine was not protective.
The researchers report that to their knowledge, this is the first time that durable protection from a single dose respiratory recombinant adenovirus-based Ebola vaccine has been demonstrated in primates.
One of the lead investigators on the study, Professor Maria Croyle and graduate student Kristina Jonsson-Schmunk of The University of Texas at Austin’s College of Pharmacy, and fellow co-author Dr. Gary Kobinger who heads the special pathogens unit at the National Microbiology Laboratory in Winnipeg, Manitoba, Canada will make a presentation on the newly published work in San Diego today (Nov. 5) at the American Association of Pharmaceutical Scientists (AAPS) Annual Meeting and Exposition 2014, the world’s largest pharmaceutical sciences meeting being held at the San Diego Convention Center Nov. 4-6
Dr. Kobinger has spent time in West Africa working with the anti-Ebola effort, and the Kobinger lab’s main research focus is to develop and test novel vaccine platforms for different applications including the protection against emerging pathogens. The new vaccine platforms that are being generated and evaluated are mainly derived from viruses, pathogenic as well as non-pathogenic (e.g. HIV, Adenovirus, AAV).
The research team’s efforts focus on modifying existing viruses at the molecular level and/or creating hybrid viruses for safe and efficient stimulation of a protective immunity against different pathogens including containment Level (CL) 4 viruses. An ongoing objective is to evaluate each vaccine strategy with the intent of identifying immune mechanisms and requirements correlating with immune protection. These findings should facilitate future selection and development of safer and more efficient vaccine strategies.
Ebola is a more often than not fatal illness that spreads among human populations primarily via direct contact with blood or bodily fluids from an infected individual. The current Ebola outbreak in Western Africa is the largest and most complex Ebola epidemic since the virus was first discovered in 1976, according to the World Health Organization. With a fatality rate currently as high as 70 percent, officials have declared this outbreak a public health emergency of international concern.
This week, the Government of Canada announced a Can$30.5 million investment and further actions to strengthen Canada’s’ domestic preparedness and international response to the Ebola outbreak in West Africa. Of that, Can$23.5 million will be in support of further research and development of Ebola medical countermeasures — namely Canada’s Ebola vaccine and monoclonal antibody treatments. This funding will be used to support clinical trials in Africa and to assist with producing monoclonal antibody treatments for Ebola to assist in the outbreak response.
The Government of Canada is contributing an additional Can$3 million to the World Health Organization (WHO) to support international security-related Ebola response activities in the West Africa region. This funding from Canada’s Foreign Affairs, Trade and Development Canada’s (DFATD) Global Partnership Program (GPP) is in addition to the Can$2.6 million previously committed to the WHO to strengthen the field response to the outbreak and to mitigate associated threats to health and security.
The Public Health Agency of Canada has also deployed two mobile laboratories in Sierra Leone to provide rapid laboratory diagnostic support and assess infection control procedures in healthcare settings. One team recently returned from a successful mission and is ready to deploy again, upon request of the World Health Organization.
To date, 800 vials of Canada’s experimental Ebola vaccine have been delivered to the WHO. The Government of Canada maintains ownership of the intellectual property associated with the VSV-EBOV vaccine. It has licensed the rights to NewLink Genetics through its wholly owned subsidiary BioProtection Systems to further develop the product for use in humans. The Agency developed two of the monoclonal antibodies contained in the Ebola treatment ZMapp. The Agency licensed their two monoclonal antibodies to http://defyrus.com Defyrus Pharmaceuticals, which sub-licensed them to MappBio Pharmaceuticals — a biotech form founded in 2003 to develop novel pharmaceuticals for the prevention and treatment of infectious diseases, focusing on unmet needs in global health and biodefense.
Dr. Croyle, Ms. Jonsson-Schmunk and colleagues at UT Austin have worked over seven years to develop a respiratory formulation that improved survival of immunized non-human primates from 67 percent to 100 percent after challenge with 1,000 plaque forming units of Ebola Zaire 150 days after immunization. They say this improvement is statistically significant because only 50 percent of the primates given the vaccine by the standard method of intramuscular injection survived challenge.
Ebola causes devastating outbreaks with fatality rates of 25 to 90 percent in Africa and Asia, and although progress has been made in understanding the virus biology, no licensed vaccines or treatments currently exist. Consequently, there is a desperate need for a vaccine that not only prevents the continued transmission from person to person, but also aids in controlling future incidences, says Ms. Jonsson-Schmunk in a UT Austin release.
“The main advantage of our vaccine platform over the others in clinical testing is the long-lasting protection after a single inhaled dose,” explains Dr. Croyle. “This is important since the longevity of other vaccines for Ebola that are currently being evaluated is not fully evaluated. Moreover, this immunization method is more attractive than an injectable vaccine given the costs associated with syringe distribution and needle safety and disposal.”
The next stage of research for Dr. Croyle’s team is a phase I clinical trial that tests the effectiveness of their vaccine in human subjects. They will also further explore preliminary data they have collected for administration of the vaccine as a thin film under the tongue in non-human primates.
This work was supported by a grant from the National Institutes of Health.
The University of Texas at Austin
National Microbiology Laboratory
World Health Organization
Office of the Honourable Rona Ambrose Federal Minister of Health (Canada)
Public Health Agency of Canada
American Association of Pharmaceutical Scientists
The University of Texas at Austin