Opko Health Inc (OPK)

[tomsylver]

SciGen, SCI-B-VAC

Enhanced immune response to hepatitis B vaccination through immunization with a Pre-S1/Pre-S2/S Vaccine ( https://opkodd.files.wordpress.com/2015/01/sci-b-vac.pdf )

February 2015, Volume 204, Issue 1, pp 57-68,
Date: 04 Jan 2015

Abstract

Efficacy and safety of recombinant yeast-derived hepatitis B vaccines for prevention of hepatitis B have been demonstrated unequivocally worldwide as reflected in reduction in HBsAg carrier rates and hepatocellular carcinoma. A new generation of recombinant HBV vaccines expressed in mammalian cells containing Pre-S/S epitopes has been developed in several countries. Such vaccines are useful in special risk groups, i.e., in non-responders to conventional HBV vaccines including older adults, obese people, health care workers, patients with renal failure and on dialysis, transplant patients, patients with HIV as well as travelers on short notice to HBV endemic regions. The future of such vaccines depends on their enhanced immunogenicity and cost profile. Sci-B-Vac™ is a mammalian cell-derived recombinant Pre-S1/Pre-S2/S hepatitis B vaccine which has been shown to be highly immunogenic, inducing faster and higher seroprotection rates against HBV with higher anti-HBs levels at lower HBsAg doses as compared to conventional yeast-derived vaccines. Recently, it has been suggested that such Pre-S/S vaccines against HBV might be efficacious not only for prevention but also for intervention in persistent HBV infection. Data obtained in a recent clinical trial conducted in Vietnam in patients with chronic hepatitis B suggest that repeated monthly i.m. injections of the Sci-B-Vac™ co-administered with daily oral lamivudine treatment can suppress HBV replication and lead to anti-HBs seroconversion in ~50 % of treated patients. Optimization of protocols and efficacy of such an intervention, intended to bypass T cell exhaustion and immune tolerance to HBV remains to be explored.

The development of a triple Pre-S1/Pre-S2/S hepatitis B vaccine

Pre-clinical studies

Sci-B-Vac™ is an aluminum hydroxide adjuvanted recombinant hepatitis B vaccine, currently manufactured by Sci- Vac Israel Ltd. The Pre-S1/Pre-S2/S vaccine was originally developed at the Weizmann Institute of Science, the Hadassah Medical Center and Biotechnology General in Israel. It was previously manufactured under the trade names Bio-Hep-B™ or Hepimmune™.

Clinical studies

To date, over 20 clinical studies have been completed in >3,000 patients immunized with Sci-B-Vac™ with an excellent safety record, including healthy adults, children and neonates [28–30, 33–39]. Additional ongoing studies are in progress in patients on hemodialysis and patients with HIV. In Israel, the Pre-S1/Pre-S2/S vaccine is in routine use for universal vaccination given on date of birth to ~50 % of all neonates (approximately 300,000 doses per year). The remaining 50 % of neonates currently receive Engerix-B®.

From the early studies and onwards, it became evident that in comparison with yeast-derived HBV vaccines, >50 % of vaccinees (neonates, children and young adults) receiving Sci-B-Vac™ develop earlier seroprotection against HBV already within 4 weeks of a single (priming) dose.

The rapid immune response to Sci-B-Vac™ was corroborated by Schumann et al. who recorded a fast and efficient cellular- and humoral-specific immune response against the envelope protein(s) of HBV using lymphocyte proliferation and Elispot assays which develops within a few weeks following the priming immunization.

The enhanced immunogenicity induced through immunization with Sci-B-Vac™ was documented in a group of 105 young adults in Israel who reached 97 and 98 % seroprotection rates at month 6, following two injections of 5 or 10 µg/dose at 0 and 1 month, respectively.

Twenty-nine patients with end stage renal disease (ESRD) who did not respond in the past to repeated immunization with a double dose of a second-generation HBV vaccination protocol received 10 µg of Sci-B-Vac™ vaccine intramuscularly at 0, 1 and 6 months. Following immunization, 25/29 patients (86 %) developed seroprotective anti-HBs levels.

Prospects of Sci-B-Vac™ as a therapeutic vaccine

* Full PDF File Med Microbiol Immunol (2015) 204:57–68 Review On Sci-B-Vac™ (Click Here) ( https://opkodd.files.wordpress.com/2015/01/sci-b-vac.pdf )