Novel methods of cell culture for production of human parvovirus B19 (B19). These specific cell lines demonstrate limited infectability and commonly produce little or no virus following initial inoculation with B19.

The present technology offers novel methods of cell culture for production of human parvovirus B19 (B19).  B19, a common infection of children adults, is the cause of fifth disease.  Symptoms of B19 infection are usually mild in otherwise healthy individuals, but some adults can suffer chronic arthopathy.  Severe health conditions and mortality may result from B19 infection of immunocompromised individuals and patients with chronic hemolytic anemia such as sickle cell disease.  In addition, B19 infection during pregnancy may cause hydrops fetalis and fetal death.  There is no specific antiviral drug for B19, and some forms of chronic infection are difficult to diagnose.  Vaccination is an effective strategy for other animal parvoviruses and is feasible for B19 in humans. 

 

B19 selectively infects erythroid progenitor cells of bone marrow, fetal liver and a small number of specialized cell lines.  These specific cell lines demonstrate limited infectability and commonly produce little or no virus following initial inoculation with B19.  Current methods for producing infectious B19 require phlebotomy of infrequently available infected donors. 

 

The available technology describes a method of producing pure populations of human erythroid progenitor cells that are fully permissive to B19 infection.   This discovery uses CD34+ hematopoietic stem cells present in peripheral blood to supply erythroid progenitor cells, which demonstrate a significant increase in viral production after initial inoculation.  The ability to efficiently generate significant amounts of infectious B19V in cells is useful for the development of killed or attenuated vaccines, therapeutics and efficient diagnostic tools for prevention and treatment of B19V.  Furthermore, this technology would allow development of new diagnostic assays, which use the entire virus as the antigenic target, thus providing more sensitive and accurate results than current diagnostic tools, which rely on antibodies against a single viral protein. 

 

Applications: 

- Diagnosis of human parvovirus B19 

- Vaccination of individuals at risk for severe effects of parvovirus infection 

- Research and development of anti-parvovirus agents

Related Publications: 

1. MC Giarratana, L Kobari, H Lapillonne, D Chalmers, L Kiger, T Cynober, MC Marden, H Wajcman, L Douay. Ex vivo generation of fully mature human red blood cells from hematopoietic stem cells. Nat Biotechnol. 2005 Jan; 23(1):69-74 .  [PubMed abs]
2. JM Freyssinier, C Lecoq-Lafon, S Amsellem, F Picard, R Ducrocq, P Mayeux, C Lacombe, S Fichelson. Purification, amplification and characterization of a population of human erythroid progenitors. Br J Haematol. 1999 Sep; 106(4):912-922.  [PubMed abs]

Preclinical

U.S. Provisional Application No. 60/808,904 filed 26 May 2006 (HHS Reference No. E-188-2006/0-US-01)

Inventors: 

Susan Wong and Neal Young (NHLBI)

Licensees Sought:  

Available for non-exclusive or exclusive licensing and commercial development.

Collaborative Research Opportunity: 

The NHLBI Hematology Branch is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize novel methods to produce parvovirus B19 and use as diagnostic or vaccine.  Please contact Dr. Neal Young at 301-496-5093, YoungNS@mail.nih.gov for more information.