CpG increases vaccine antigen-specific cell-mediated immunity when administered with hepatitis B vaccine in HIV infection - PubMed (original) (raw)

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

Jonathan B Angel et al. J Immune Based Ther Vaccines. 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.

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Figures

Figure 1

Figure 1

Proliferative responses to hepatitis B surface antigen (HBsAg). Proliferative responses to HBsAg, measured as counts per minute (cpm) of 3H-thymidine incorporation. *Repeat measures ANOVA week 4, 8, 12, p = 0.0039, n = 38; week 24, 48, p = 0.02714, n = 38.

Figure 2

Figure 2

Proliferative responses to hepatitis B surface antigen (HBsAg). A) stimulation index (SI) or B) change in SI from baseline are enhanced over the 48 week study period in subjects that received hepatitis B vaccine plus CpG (solid line; n = 19) as compare to those that received hepatitis B vaccine alone (broken line (n = 19) *p 0.04 by Mann Whitney U Test.

Figure 3

Figure 3

Proliferative responses to HIV p24 antigen. Proliferative response to HIV p24 Ag evaluated as A) cpm or B) SI, did not change over the 48 week study period in either subjects that received hepatitis B vaccine plus CpG (solid line; n = 19) or those that received hepatitis B vaccine without CpG (broken line; n = 19).

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