A Pilot Study of SRL 172 (Killed Mycobacterium vaccae) in Healthy Chronic Hepatitis B Carriers and Hepatitis B Vaccine Non-Responders

Abstract

Aim: To assess possible development of immunity to HBV by the use of hepatitis B vaccine in combination with the adjuvant M. vaccae (SRL 172) in healthy chronic HBsAg carriers and in healthy non-responders to hepatitis B vaccine. Hypothesis: To utilise the known immuno-stimulatory effects of SRL 172 (heat-killed M. vaccae) on chronic carriers of HBV and non-responders to hepatitis B vaccine to overcome the respective ‘immune-tolerance’ and ‘immune blindness’ observed in these conditions and develop immunity to hepatitis B.

Method: 35 suitable healthy HBsAg carriers were randomised to receive hepatitis B vaccine together with either placebo or SRL172 by the intradermal route on one occasion. 23 HB vaccine non-responders were randomised in the same way, and similarly given vaccine with either SRL 172 or placebo. The HBsAg carrier subjects were followed-up for 12 months to monitor changes in HBV markers, anti-HBs, clinical chemistry, immunological and clinical status. The HB vaccine non-responders were reassessed for the development of anti-HBs at 3 months post-immunisation.

Results: This pilot study provided evidence that SRL172 was moderately well tolerated and safe. One HB vaccine/placebo recipient (with initial pre-vaccination high HBV load) became HBV DNA negative and remained so for the 12 month duration of the study. Vaccine plus SRL172 helped induce measurably higher anti-HBs titres in HB vaccine non-responders, however, because of relatively small participant numbers, statistically significant results were not obtained.

Conclusion: Based on the development of anti-HBs in non-responders, the non-proprietary mixing of vaccine with SRL172 does not destroy immunogenicity of the vaccine and thus provides an opportunity to conduct further studies of this combination in hepatitis B vaccine non-responders. HB vaccine plus SRL 172 when given on one occasion is ineffective in treating HBsAg carriers. Interesting differences between the treatment groups were observed in HB viral load responses at 3 months post-vaccination. Consideration should be given to further studies using multi-dose HB vaccine regimens.