Hepatitis B vaccination in chronic kidney disease patients: a call for novel vaccines

Abstract

The protective immunization rates in response to hepatitis B vaccination in chronic kidney disease (CKD) patients are lower than response rates in the general population because of genetic and CKD-related factors as well as logistic problems with a proper providing of the recommended vaccination schedules. This review focuses on third-generation vaccines and adjuvanted vaccines commercially introduced in some countries, investigated in clinical trials, especially involving CKD patients or used only in the experimental studies. In order to improve the immunization rate, the use of third-generation vaccines (yeast-derived pre-S2/S HBV vaccines, mammalian cell-derived pre-S2/S HBV vaccines, mammalian cell-derived pre-S1/pre-S2/S HBV vaccines), novel adjuvants (AS04, AS02, phosphorothioate oligodeoxyribonucleotide, hemokinin-1, a polysaccharide based on delta inulin, nano-complex Hep-c, cyclic diguanylate) or immunostimulants for enhancement of immunogenicity of existing recombinant hepatitis B vaccines is tried to improve results of hepatitis B vaccination prior to dialysis commencement or already on renal replacement therapy.

Keywords::

• adjuvants
• chronic kidney disease
• dialysis
• hepatitis B vaccination
• immunization rate
• immunocompromised state
• renal transplantation
• third-generation vaccines

Acknowledgements

The author would like to dedicate this paper to BS Blumberg and IMillman who developed the hepatitis B vaccine.

Financial & competing interests disclosure

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Inherited non-responsiveness to hepatitis B vaccination is associated not only with polymorphisms within HLA complex, but also in genes encoding cytokines and their receptors.

• All diabetics should be vaccinated against HBV infection at the diagnosis of their disease.

• Non-responsiveness to hepatitis B vaccination is associated with infection-cause mortality and shorter survival probability of renal replacement therapy patients.

• Vitamin D deficiency is mentioned as acquired chronic kidney disease (CKD)-related factor contributing to impaired seroconversion after hepatitis B vaccination.

• At present, there is no strong evidence for the use of third-generation hepatitis B vaccines in CKD patients.

• Hepatitis B vaccine adjuvanted with AS04, already licensed in Europe, is more effective in CKD patients than the standard recombinant vaccine and should be used at least in non-responders to the recommended vaccination regimen.

• Hepatitis B vaccines, adjuvanted with AS02 or cytosine phosphoguanosine oligonucleotides, are more potent in CKD patients than the standard recombinant vaccine, but are not licensed yet.

• Hemokinin-1, a polysaccharide based on delta inulin, nano-complex Hep-c, and cyclic diguanylate are investigated as possible HBV surface antigen adjuvants in animals, and the experimental results are promising.