CpG oligodeoxynucleotides improve the response to hepatitis B immunization in healthy and SIV-infected rhesus macaques.
OBJECTIVE
The development of an immunogenic vaccine against hepatitis B virus (HBV) is particularly important for HIV-infected patients since shared epidemiological risks result in HIV-infected subjects having a high incidence of HBV, and coinfection with HBV increases the occurrence of hepatotoxicity with antiretroviral therapy. Although HBV vaccination is recommended to all HIV-positive patients, its efficacy in these patients is reduced.


METHODS
Healthy (n = 15) and SIV-infected (n = 17) rhesus macaques were immunized with Engerix B alone or combined with type D or type K CpG ODN. SIV plasma RNA levels were determined by a real time reverse transcriptase polymerase chain reaction and antibody titers to HBV surface antigen (HbsAg) were measured by enzyme-linked immunosorbent assay every 2 weeks.


RESULTS
In healthy macaques, adding D or K ODN to Engerix B accelerated and boosted the titer of the anti-HbsAg response. In SIV-infected macaques, Engerix B alone elicited no detectable antibody response but a significant response was seen when it was combined with K or D ODN. The antibody titer induced by vaccinating HIV-infected macaques was inversely correlated with their initial viral load, with animals having > 10(7) copies/ml being unable to mount a significant response. No adverse events or changes in SIV viral load were evident during the study.


CONCLUSIONS
These findings support the development of clinical studies to assess the use of CpG ODN as an adjuvant for HBV vaccination in healthy and immunocompromised HIV-infected subjects.
Verthelyi
Daniela
D
Division of Therapeutic Proteins, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA.
Wang
Vivian W
VW
Lifson
Jeffrey D
JD
Klinman
Dennis M
DM
D000276:Adjuvants, Immunologic; D000818:Animals; D006509:Hepatitis B / Q000517:prevention & control; D006510:Hepatitis B Antibodies / Q000096:biosynthesis*; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D017325:Hepatitis B Vaccines / Q000276:immunology*; D016867:Immunocompromised Host; D007074:Immunoglobulin G / Q000096:biosynthesis; D008253:Macaca mulatta; D009838:Oligodeoxyribonucleotides / Q000276:immunology*; D012367:RNA, Viral / Q000097:blood; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000302:isolation & purification; D014614:Vaccines, Synthetic / Q000276:immunology*; D019562:Viral Load
D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; C075654:Engerix-B; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D007074:Immunoglobulin G; D009838:Oligodeoxyribonucleotides; D012367:RNA, Viral; D014614:Vaccines, Synthetic