Hepatitis B Vaccination Induced TNF-α- and IL-2-Producing T Cell Responses in HIV− Healthy Individuals Higher than in HIV+ Individuals Who Received the Same Vaccination Regimen

We investigated cytokine production and expression of degranulation marker CD107a after different strategies of hepatitis B virus (HBV) vaccination in human immunodeficiency virus-infected individuals, which were three doses of 20 μg (standard dose group), four doses of 20 μg (four doses group), or four doses of 40 μg (four double doses group), compared to standard dose vaccination in healthy controls. PBMCs collected at different time points were stimulated in vitro with recombinant hepatitis B surface antigen and analyzed by flow cytometry. There was an increase in TNF-α production of total and memory CD4+ T cells at 7 months after vaccination in healthy controls compared to the HIV+ group, which received the same standard vaccination regimen. An increase in the IL-2-producing memory CD4+ T cells in the healthy control group was also observed at 7 months after vaccination. No differences were observed between the healthy controls and both groups of four doses at any time point of study. These results suggest that the standard HBV vaccination schedule might induce better production of TNF-α and IL-2 from CD4+ T cells in healthy individuals. Modification of HBV vaccination schedule by increasing the frequency and/or dosage may improve the CMI response in HIV-infected individuals. This trial is registered with NCT1289106

Geometric mean titers of anti-HBs antibody by vaccination regimen.

<p>Geometric mean titers of anti-HBs antibody by vaccination regimen.</p

Comparison of Immunogenicity and Safety of Four Doses and Four Double Doses vs. Standard Doses of Hepatitis B Vaccination in HIV-Infected Adults: A Randomized, Controlled Trial

<div><p>Background</p><p>HBV vaccination is recommended in HIV-infected adults with CD4+ cell count >200/mm³ although the efficacy is only 33.3% -65%. We conducted a randomized, controlled trial to evaluate the efficacy and safety of three regimens of HBV vaccination at Chiang Mai University Hospital, Thailand.</p> <p>Methods</p><p>From February 4, 2011 to May 4, 2012, 132 HIV-infected adults with CD4+ cell counts >200 cells/mm³, undetectable plasma HIV-1 RNA, and negative for all HBV markers were randomly assigned to receive one of three recombinant vaccine (Hepavax-Gene^® Berna, Korea) regimens: 20 μg IM at months 0, 1, and 6 (Standard doses group, n=44), 20 μg IM at months 0, 1, 2, 6 (four doses group, n=44), or 40 μg IM at months 0, 1, 2, and 6 (four double doses group, n=44). The primary outcomes were to compare the immunogenicity and safety between the four-doses groups with the Standard doses group.</p> <p>Results</p><p>At months 7 and 12, the percentages of responders (anti-HBs ≥10 mIU/mL) were 88.6% and 70.4% in the Standard doses group, 93.2% and 86.4% in the four doses group, (<i>P</i>=0.713 and 0.119), and 95.4% and 88.6% in the four double doses group, (<i>P</i>=0.434 and 0.062), respectively. Factors associated with a high titer level (anti-HBs ≥100 mIU/mL) were vaccination schedule and younger age. The most common adverse event was pain at the injection site (42.4%); this was significantly more frequent in the four double doses group compared to the Standard doses group. No serious adverse events were observed.</p> <p>Conclusions</p><p>In Northern Thailand, the standard three-doses HBV vaccination in HIV-infected adults with CD4+ cell counts >200 cells/mm³ and undetectable plasma HIV-1 RNA is highly effective. Although regimens of four injections of either standard or double doses could not significantly increase the response rate, these regimens may induce higher levels of antibody to the virus.</p> <p>Trial registration information: ClinicalTrials.gov; NCT1289106; <a href="http://clinicaltrials.gov/ct2/show/NCT01289106" target="_blank">http://clinicaltrials.gov/ct2/show/NCT01289106</a></p> </div

Percentages of responders (anti-HBs ≥ 10 mIU/ml) to hepatitis B vaccine by vaccination regimen.

<p>Percentages of responders (anti-HBs ≥ 10 mIU/ml) to hepatitis B vaccine by vaccination regimen.</p

Consort diagram of participants.

<p>Consort diagram of participants.</p

Percentages of responders (anti-HBs ≥ 100 mIU/ml) to hepatitis B vaccine by vaccination regimen.

<p>Percentages of responders (anti-HBs ≥ 100 mIU/ml) to hepatitis B vaccine by vaccination regimen.</p