Whole Organism Vaccines
Using live attenuated or killed organisms to elicit immune protection can be traced back to the early part of the 20th century following the achievements of Jenner and Pasteur in the vaccine field. Killed or inactivated vaccines have used with relative success to combat such disease as tuberculosis, influenza, smallpox, and polio. In the case of the Ebola virus several attempts have been made towards developing safe attenuated or killed viral vaccines, but none has been successful thus far. Due to the many safety concerns surrounding the use of inactivated or attenuated pathogens as protective agents, all of the reported studies using attenuated live Ebola virus have been carried out using non-primate or non-human primates as animal models. For instance, in the 1980’s HW Lupton et al vaccinated guinea pigs with a formalin-fixed virion preparation and reported partial protection of the animals against wild type viral challenge. However, to the best of our knowledge, this study has not been replicated in non-human primates.
In a 1994 study published by a group in Russia led by V Mikhailov, hamadryas baboons were vaccinated with an inactivated preparation of Ebola. The study showed that 4 of the 5 baboons were completely protected (Mikhailov VV, et al. An evaluation of the possibility of Ebola fever specific prophylaxis in baboons (Papio hamadryas). However, results from subsequent studies performed by another group in 1995 using a similar protocol suggested that the protection elicited by the inactivated viral vaccine was insufficient to protect the baboons from lethal challenge.
In 2002 a group led by Thomas Geisbert at the U.S. Army Medical Research Institute of Infectious Diseases evaluated several DNA vaccine formulations in macaques, two of the four vaccines tested included a liposome formulation containing encapsulated, gamma-irradiated Ebola particles in liposomes containing lipid A and a concentrated, gamma-irradiated whole-virion preparation.
In the case of the liposomal-based preparation, they injected 3 cynomolgus monkeys intravenously with 1-ml of the preparation at days 0, 28, and 55. Four macaques served as negative control. All tested animal received 1,000 plaque-forming units (PFU) of the EBOV-Z subtype, which was isolated from a patient who contracted the disease in an outbreak in 1995 45 days after the third vaccination. All of the animals in both groups died at some point after the challenge.
For the heat inactivated whole virion formulation, the viral particles were inactivated by gamma ray exposure. The injections were done subcutaneously. Two cynomoulgous monkeys and two rhesus monkeys were injected at a 50-ug concentration in RBI adjuvant. The immunization schedule was repeated 7 and 35 days after the initial vaccination. As in the liposomal experiment, four macaques were included in the negative control group. Challenge with EBOV-Z occurred 35 days after the last injection. All of the animal subjects in the group, with the exception of a rhesus macaque that was vaccinated with the irradiated particles, succumbed to the viral attack and perished.
Although genetic manipulation of disease-causing pathogens has become more feasible over the past 15 years paving the way for the development of potentially safer and more effective inactivated vaccine formulations in the future, there is a need for an immediate and effective vaccine for the Ebola virus and its less virulent relative. Other vaccines are being tested, some the most promising are based on recombinant DNA vaccination.
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This page last updated: 14 April 2004.
