Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector – Virus or component thereof
Patent
1996-05-22
1998-03-17
Knode, Marian C.
Drug, bio-affecting and body treating compositions
Antigen, epitope, or other immunospecific immunoeffector
Virus or component thereof
424 936, 435236, 435237, 435239, 435948, A61K 3925, C12N 704, C12N 708, C12N 702
Patent
active
057283869
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
This invention is concerned with the provision of a thermostable varicella virus for vaccine production. Varicella zoster virus (VZV) causes chicken-pox and zoster (shingles). Chickenpox is a highly contagious disease that occurs in persons with no VZV immunity. More than 90% of the population is exposed during the first two decades of life. The disease is a severe threat to the immunosuppressed and to adults. In many cases, VZV becomes latent in dorsal root ganglion cells. Shingles, a painful chronic condition, occurs when VZV is reactivated from the latent state.
Prevention of chickenpox by vaccination is a desirable goal, and the institution of universal childhood vaccination with a live attenuated varicella vaccine is envisioned. The prior art has reported the propagation of VZV in various cell culture systems and the use of live, attenuated, cell-free VZV as a vaccine. U.S. Pat. No. 3,985,615 describes the production in guinea pig primary embryonic cells of attenuated varicella virus. Virus produced according to that process, the Oka strain of VZV, is suitable for vaccine use and has been deposited with the ATCC as VR-795, although other strains of varicella may be used to produce attenuated VZV according to the U.S. Pat. No. 3,985,615 and other known processes (see U.S. Pat. Nos. 5,024,836; and 4,000,256). U.S. Pat. No. 4,008,317 describes the cultivation of a temperature-sensitive mutant of VZV in WI-38 cells. Compositions useful for the maintenance of viable VZV, such as SPGA, are also known in the art, (see U.S. Pat. Nos. 4,147,772; 4,000,256; 4,337,242, and 4,338,335).
VZV is a member of the herpesvirus family. VZV has been isolated and provided as a live attenuated virus vaccine which is effective to prevent varicella infection in children (U.S. Pat. Nos. 3,985,615; 4,000,256; 5,024,836). No effective, inactivated VZV vaccine has been developed, and VZV rapidly loses viability at ambient temperatures. Thus, a constant problem with VZV vaccines of the past has been the need to store the virus at temperatures below freezing point. This has typically meant that the live attenuated vaccine, even when lyophilized, must be stored in a stabilizing medium at reduced temperatures, such as -15.degree. C. or -20.degree. C. Under these conditions, the live attenuated vaccine viability half-life is approximately 36 months. At -70.degree. C., the haft life is much longer (on the order of many years). However, where the live attenuated vaccine must be stored at higher temperatures, such as at 4.degree. C. or higher, as in third world countries where refrigeration of vaccines at any temperature is difficult, the virus viability drops off very rapidly. Thus, there has been a need for a more stable live attenuated VZV vaccine. This invention meets that need.
SUMMARY OF THE INVENTION
A thermostable live attenuated varicella zoster virus (tVZV) is produced by selection and growth of virus which survives heat inactivation. It was not predictable that heat stable VZV would be produced. The tVZV is useful to produce a new live attenuated varicella zoster virus vaccine with innately increased thermostability.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1: Linear regression curve showing thermostability of the new tVZV of this invention at 35.degree. C.
DETAILED DESCRIPTION OF THE INVENTION
Varicella zoster virus (VZV) can be isolated from the papular eruptions of children in the acute phase of chickenpox. VZV isolated in this manner is cultured in vitro over multiple passages to produce a live, attenuated virus. This can be accomplished according to U.S. Pat. No. 3,985,615, hereby incorporated by reference.
According to one embodiment of the instant invention, a live attenuated VZV vaccine is lyophilized after culture and attenuation according to methods known in the art. The lyophilized virus is then subjected to an extended period, about 5-19 days, at an elevated temperature, 25.degree.-75.degree. C. Following the inactivation cycle, residual viable virus is recovered and selected in
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Provost Philip J.
Wadsworth Cathy Warren
Coppola Joseph A.
Knode Marian C.
Merck & Co. , Inc.
Tribble Jack L.
Wortman Donna C.
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