Patent Application
20080131449
The present invention generally relates to the use of selected polypeptides from African Swine Fever virus for the prevention and therapy of African Swine Fever infections as well as other infections, including immune deficiencies in mammals and humans.
African Swine Fever is an endemic disease in sub-Saharan Africa and many other parts of the developing world. It is caused by the African Swine Fever virus that primarily replicates in macrophages and monocytes leading to the impairment of the structure and function of the immune system of the infected organisms. Until now the African Swine epidemic continues to spread despite all efforts to contain it. Thus, there is an objective need for effective, safe and affordable preventive and therapeutic approaches, in particular for effective vaccines, to control and eventually eradicate this disease.
Since the characteristic feature of the African Swine Fever virus is to impair the immune system and to cause immune deficiencies in its hosts the development of vaccines and other therapeutic approaches against the African Swine Fever virus has implications for other immune deficiencies or diseases. Several other viruses are also known to cause immunodeficiency-like syndromes in humans, including cytomegalovirus, Epstein Barr Virus, HIV and others. Moreover, a series of cases of so-called “idiopathic” immunodeficiencies have been documented that display CD4+ T-lymphocytopenia with opportunistic infections, but show no evidence of HIV infection (1).
Since antibodies for the African Swine Fever virus have been detected in humans, the possibility of human infection with the African Swine Fever virus exists and may thus far have escaped any systematic screening. Thus, any preventive and therapeutic approach to African Swine Fever can have far-reaching implications to control immune deficiency conditions in humans.
Synthetic oligopeptides prepared from African Swine Fever virus proteins are effective in prevention, treatment and diagnosis of African Swine fever as well as for immune deficiencies in humans.
Oligopeptides are identified and selected by means of suitable algorithms from the known amino acid sequence of pathogenicity-mediating African Swine Fever virus proteins. Subsequently, these oligopeptides are tested in vitro for their ability to decrease or completely block infection by the African Swine Fever virus (prevention and therapy) or for their ability to raise antibodies to detect the virus (diagnosis). Ultimately, the successfully tested African Swine Fever virus oligopeptides can be used in veterinary and clinical medicine.
The relative peaks of this algorithm, defined as amino acid sequence regions of either high hydrophilic characteristics or sequence regions of higher hydrophilic characteristics in relation to adjacent amino acid sequences or in comparison to hydrophobic regions of the protein, represent the likely candidate sequence regions (oligopeptides) serving as epitopes (antigens) for antibody formation. Moreover these defined oligopeptide sequences represent the likely region by which a protein interacts with other proteins and/or biological compounds in an organism, including those interactions that mediate infection or other forms of pathogenicity.
Producing synthetic oligopeptides, corresponding to these algorithm maxima allows the development of preventive and therapeutic agents to control African Swine Fever virus infections. The relative peaks of the Hopp-Woods algorithm for the p54 protein of the African Swine Fever virus selected for this patent application are marked by arrows. The synthetic oligopeptides for the other African Swine Fever Virus proteins specified in this disclosure and the claims are selected in an analogous way.
The African Swine Fever virus is a particular virus the pathogenicity of which is largely determined by targeting the immune system of the host and disabling it.
Despite the DNA sequence of African Swine Fever virus having been determined (3), there is currently no effective vaccine available to control African Swine Fever as documented in the United Nations Food and Agricultural Organization's field handbook on this disease (4)
The present invention describes the identification and production of preventive and therapeutic agents, which—among others—can be used as vaccines against African Swine fever with the following specific steps being taken:
The current invention also describes the application of the current invention for the diagnosis and treatment of immune deficiency conditions in mammals.
The following are the characteristics of the African Swine Virus:
While the African Swine Fever virus has been primarily detected in pigs and certain other animals, antibodies against the African Swine Fever virus have also been found in humans (5). The fact that there was no description of any finding of the African Swine Fever virus in humans may thus be attributable to oversight or a lack of understanding for the significance of African Swine fever virus for the pathogenicity of immune deficiencies in humans.
Thus, the inventions described in this patent application can have far reaching implications not only for the control of African Swine fever but also for the control of other immunodeficiency diseases.
The main structural and/or pathogenicity mediating proteins of the African Swine virus are the following:
Protein p10 of the African Swine Virus has the following relative hydrophilic peaks:
Protein p11.5 of the African Swine Virus has the following relative hydrophilic peaks:
Protein p12 of the African Swine Virus has the following relative hydrophilic peaks:
Protein p14.5 of the African Swine Virus has the following relative hydrophilic peaks:
Protein p17 of the African Swine Virus has the following relative hydrophilic peaks:
Protein p22 of the African Swine Virus has the following relative hydrophilic peaks:
Protein p30 of the African Swine Virus has the following relative hydrophilic peaks:
Protein p54 of the African Swine Virus has the following relative hydrophilic peaks:
Protein p72 of the African Swine Virus has the following relative hydrophilic peaks:
Proliferating Antigen-Like Proteins with Relative Hydrophilic Peaks
1. Duncan R A et al. Idiopathic CD4+ T-lymphocytopenia—four patients with opportunistic infections and no evidence of HIV infection. N Engl J Med. 1993; 328(6): 393-8.
2. Rodriguez F et al. Characterization and molecular basis of heterogeneity of the African Swine Fever virus envelope protein p54. J Virol 1994; 68 (11): 7244-7252.
3. Yanez R J et al. Analysis of the complete nucleotide sequence of African Swine Fever virus. Virology 1995; 208: 249-278.
4. Recognizing African Swine Fever, A Field Manual, UN Food and Agricultural Organization, ISBN 92-5-104471-6
5. Hess W R. African Swine Fever: A Reassessment. Advances in Veterinary Science and Comparative Medicine Vol. 25. Cornelius C E, Simpson C F eds. Academic Press, New York, 1981:39-69.
