Immune responses in patients with HIV infection after vaccination with recombinant Hepatitis B virus vaccine

Abstract

Background: Patients with HIV infection are at risk of co-infection with HBV, as the routes of transmission are shared and thus immunization with HBV vaccine could be protective in them. The aim of the present study was to assess the efficacy of recombinant vaccine in treatment-naive HIV positive patients and healthy controls, and to dissect out differences if any, in different limbs of immune response.

Methods: Forty HIV positive patients and 20 HIV negative controls, negative for HBsAg, HBsAbs and HBcAbs were vaccinated with three doses of 40 microg and 20 microg of vaccine respectively. Patients were divided into high CD4 and low CD4 group based on CD4+ lymphocytes of 200 and < 200/mm3 respectively. Group II consisted of healthy controls. Detection of phenotypic markers was done by flowcytometry. Cytokine estimation was done by sandwich ELISA. HBsAbs were estimated in serum by ELISA.

Results: After vaccination, CD4+, CD8+ and CD3+ cells increased significantly in all the groups. There was no increase in NK cell activity in patients with high CD4+ lymphocytes and only a marginal increase in patients with low CD4+ lymphocytes (170 to 293/mm3) whereas a marked increase was observed in controls (252 to 490/mm3). After vaccination, although an increase in memory cells was observed in HIV positive patients, yet HBsAb levels were significantly lower than controls (P < 0.05) indicating a functional defect of memory cells in HIV/AIDS patients. Basal IFN-gamma levels were also significantly lower in HIV/AIDS patients (P < 0.01). Although the levels increased after vaccination, the peak level remained lower than in controls. HBsAb titers were much lower in HIV positive patients compared to controls. (High CD4+ group: 8834 mIU/ml, low CD4+ group: 462 mIU/ml Vs.

Controls: 16,906 mIU/ml). IL-4 and IL-10 were low in patients.

Conclusion: Despite a double dose in patients, IL-4 and IL-10, which regulate antibody response, were also lower in patients, and this together with low CD4+ counts and lack of T help, accounted for low HBsAb levels. Vaccination in patients with CD4+ lymphocytes < 50/mm3 was ineffective. Thus early immunization is advocated in all HIV positive patients at a stage when they are still capable of mounting an adequate immune response.

Figure 1

Schematic representation of tests conducted with time schedule.

Figure 2

Flowcytometric analysis of CD₄/CD₈ lymphocytes in patient with low CD₄ counts. FL 1 shows FITC labeled CD₄⁺ T lymphocytes. FL 2 shows PE labeled CD₈⁺ T lymphocytes. Note an increase of CD4 ⁺ lymphocytes from 0.06% at stage B to 10% at stage F.

Figure 3

Comparative mean CD₄ lymphocyte counts between the various groups.

Figure 4

Flowcytometric analysis of CD_45RA⁺ Naïve T cells in patient with low CD₄ counts. FL 1 shows FITC labeled CD_45RA⁺ naïve T lymphocytes. Note an increase of CD45RA ⁺ naïve T cells from 34% at stage B to 56% at stage D.