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CpG oligodeoxynucleotides improve the response to hepatitis B immunization in healthy and SIV-infected rhesus
Daniela Verthelyi1, Vivian W Wang, Jeffrey D Lifson
1Division of Therapeutic Proteins, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA.
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.
