Original research

CpG increases vaccine antigen-specific cell-mediated immunity when administered with hepatitis B vaccine in HIV infection

Jonathan B Angel^1,2* , Curtis L Cooper^1,2 , Jennifer Clinch¹ , Charlene D Young¹ , Andreane Chenier¹ , Karl G Parato¹ , Michael Lautru¹ , Heather Davis³ and Donald W Cameron^1,2

¹  Ottawa Health Research Institute, 501 Smyth Rd., Ottawa, ON, K1H 8L6, Canada

²  Division of Infectious Diseases, University of Ottawa, Ottawa Hospital – General Campus, 501 Smyth Rd., Ottawa, ON, K1H 8L6, Canada

³  Coley Pharmaceuticals, 340 Terry Fox Dr., Suite 200, Ottawa, ON, K2K 3A2, Canada

author email corresponding author email* Contributed equally

Journal of Immune Based Therapies and Vaccines 2008, 6:4doi:10.1186/1476-8518-6-4

Published:	12 August 2008

Abstract

Background

Lack of adequate adjuvancy is a possible explanation for lack of vaccine immunogenecity. Immunostimulatory CpGs are potent vaccine adjuvants and may be an important component of the development vaccines, particularly those for which a cellular immune response is required for protection. We have previously demonstrated that CpG ODN co-administration with hepatitis B vaccine results in earlier, stronger and more sustained antibody responses to hepatitis B surface antigen in HIV infected individuals, and wished to determine if, in this population, helper T-cell responses were also enhanced.

Methods

We conducted a double-blind, placebo-controlled trial in hepatitis B susceptible, effectively treated HIV-seropositive individuals. Participants received hepatitis B vaccine, with either placebo or CPG 7909 1.0 mg at week 0, 4 and 8. To determine the impact of CpG on cellular immune responses, lymphoproliferative responses (LPR) were evaluated by [³H]-thymidine incorporation at baseline and weeks 4, 8, 12, 24, and 48. Immunophenotyping of lymphocyte subsets was also determined at these time points.

Results

Of 36 patients enrolled, 18 received hepatitis B vaccine alone, and 18 received hepatitis B vaccine with CpG. Inclusion of CPG 7909 was associated with a greater proliferative response to HBsAg at all time points following initial vaccination. This increase was statistically significant at 8 weeks (p = 0.042) and 48 weeks (p = 0.024). Similar results were observed when LPR were evaluated as stimulation indices (SI). No differences in proliferative responses to HIV p24 Ag were observed, nor were there any differences in lymphocyte subsets.

Conclusion

In addition to enhancing humoral responses to vaccination, we describe for the first time that CPG 7909 enhances cellular immunity to vaccine antigen in a typically hyporesponsive population. This adjuvancy may be important in the development of an effective vaccine for which a cellular immune response is required for protection.