About The Study

The primary objective of the study was to assess the safety of CpG ODN 7909 in adjuvant doses, and the safety and immune effect of CpG ODN 7909 as an adjuvant to a Engerix B vaccine, an hepatitis B (HB) vaccine, in HIV-infected volunteers who had not been vaccinated or who had sub-protective level of HB antibodies despite prior vaccination.

Study Approach

This was a phase Ib/IIa, randomized, double-blind, placebo-controlled single centre study. HIV-seropositive participants with viral load below detection and CD4 counts above 200 cells/mm3 were divided evenly into three study arms based on their HB virus immune status. Non-HBV vaccinated participants with no serologic evidence of previous infection were enrolled in the susceptible arm. The hyporesponsive arm consisted of those with anti-HBV titres below 10 mIU/mL following previous HBV vaccination. People in the susceptible arm were randomly allocated to receive either a double dose of Engerix-B (40 ug HBsAg + alum) at 0, 1 and 2 month(s) OR a double dose of Engerix-B (40 ug HBsAg + alum) plus 1 mg CpG ODN 7909 at 0, 1 and 2 month. An immune arm consisting of those with HB antibodies above 10 mIU/mL made up a third study arm. They received CpG ODN 7909 or placebo. This arm was required to assess the potential of CpG ODN 7909 as an immune modulator. Serologic response to HBV vaccination, CD4 lymphocyte count, HIV viral load, and in vitro measures of cell mediated immunity were assessed at intervals over the 24 weeks of follow-up. Seroconversion (SC) was defined as HB antibody presence above 1 mIU/mL, and seroprotection (SP) was defined as HB antibody presence above 10 mIU/mL.

Population

The study enrolled fifty-eight adult HIV-infected volunteers on HAART with viral load below 50 copies per mL and CD4 count above 200 cells per mm3. Nineteen had never been vaccinated for hepatitis B, and nineteen had sub-protective level of HB antibodies despite prior vaccination. Another twenty participants were in the immune arm.

Results

Vaccination was well tolerated. One participant experienced urticaria (hives). Levels of CD4 counts and suppression of HIV viral load were maintained.

At week 6, 74% of the participants in the control group, vaccinated with Engerix-B alone, seroconverted and 53% had reached a protective level of HB antibody response. The percentages at week 8 were 84% and 53% respectively, and they were 100% and 95% at week 12. Seroprotection occurred significantly earlier in the group receiving the CpG adjuvant, with 95% of the participants with SC at week 6, and 89% with SP (95% and 89% at week 8, and 94% for SC and SP at week 12). Mean antibody response was higher in the CpG group at all time. In the participants with prior vaccine failure, significantly more in the CpG group had a durable HB antibody response (above 100 mIU/mL at 24 weeks) (67% CpG versus 10% control).

Conclusion

This small controlled study showed safety and tolerance of CpG ODN 7909 as adjuvant to accelerated double-dose Engerix-B in treated HIV infection. Participants with no prior HB vaccination in the CpG group reached a protective level of HB antibody significantly more rapidly, and they maintained higher HB antibody response. In the group with prior HBV vaccine failures, significantly more participants in the CpG group maintained durable HB antibody response.

Note: These results were taken from an abstract presented at CROI 2003.

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