GM-CSF Fails to Improve Immune Responses to Booster Hepatitis B Vaccination in HIV-Infected Individuals
TL;DR: In this article, the authors randomized 60 HIV-infected subjects to receive a booster dose of HBV vaccine with 250mcg GM-CSF as an adjuvant or booster vaccine alone.
Abstract: Background: Hepatitis B (HBV) vaccination is an important preventive intervention for HIV-infected population. Data regarding booster HBV vaccine for persons with low HBV surface antibody (sAb) titers after vaccination in this immunocompromised population is lacking. Methods: We randomized 60 HIV-infected subjects lacking HBV protection after completion of 3 doses of HBV vaccine to receive a booster dose of HBV vaccine with 250mcg GM-CSF as an adjuvant or booster vaccine alone. Results: GM-CSF was safe with expected side effects. However, only 35% of persons receiving GM-CSF developed protective sAb while 50% in vaccine only arm developed protection (P = 0.47). Overall, only 28% of subjects maintained protective sAb 1 year after vaccination. Conclusions: GM-CSF failed to improve responses to the booster HBV vaccination. Overall, response was poor with only 42% of persons responding at one month post-vaccination confirming booster vaccination with the current HBV vaccine has poor immunogenicity among HIV-infected persons. Further research is needed to develop optimal vaccination strategies in HIV-infected persons.
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TL;DR: To reduce the disease burden of HBV infection among HIV-infected patients, adoption of safe sex practices, avoidance of sharing needles and diluent, HBV vaccination and use of cART containing tenofovir disoproxil fumarate plus emtricitabine or lamivudine are the most effective approaches.
Abstract: Hepatitis B virus (HBV) infection is a leading cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma worldwide. Due to the shared modes of transmission, coinfection with HBV and human immunodeficiency virus (HIV) is not uncommon. It is estimated that 10% of HIV-infected patients worldwide are coinfected with HBV. In areas where an HBV vaccination program is implemented, the HBV seroprevalence has declined significantly. In HIV/HBV-coinfected patients, HBV coinfection accelerates immunologic and clinical progression of HIV infection and increases the risk of hepatotoxicity when combination antiretroviral therapy (cART) is initiated, while HIV infection increases the risk of hepatitis events, cirrhosis, and end-stage liver disease related to chronic HBV infection. With the advances in antiviral therapy, concurrent, successful long-term suppression of HIV and HBV replication can be achieved in the cART era. To reduce the disease burden of HBV infection among HIV-infected patients, adoption of safe sex practices, avoidance of sharing needles and diluent, HBV vaccination and use of cART containing tenofovir disoproxil fumarate plus emtricitabine or lamivudine are the most effective approaches. However, due to HIV-related immunosuppression, using increased doses of HBV vaccine and novel approaches to HBV vaccination are needed to improve the immunogenicity of HBV vaccine among HIV-infected patients.
79 citations
TL;DR: Recent advances on the roles of various cytokines in different phases ofHBV infection and cytokine-related mechanisms for impaired viral control and liver damage during HBV infection are discussed, and experimental therapeutic applications of cytokines are focused on to gain a better understanding of this newly emerging aspect of disease pathogenesis.
Abstract: Hepatitis B virus (HBV) infection is a worldwide health problem, with approximately one third of populations have been infected, among which 3–5 % of adults and more than 90 % of children developed to chronic HBV infection. Host immune factors play essential roles in the outcome of HBV infection. Thus, ineffective immune response against HBV may result in persistent virus replications and liver necroinflammations, then lead to chronic HBV infection, liver cirrhosis, and even hepatocellular carcinoma. Cytokine balance was shown to be an important immune characteristic in the development and progression of hepatitis B, as well as in an effective antiviral immunity. Large numbers of cytokines are not only involved in the initiation and regulation of immune responses but also contributing directly or indirectly to the inhibition of virus replication. Besides, cytokines initiate downstream signaling pathway activities by binding to specific receptors expressed on the target cells and play important roles in the responses against viral infections and, therefore, might affect susceptibility to HBV and/or the natural course of the infection. Since cytokines are the primary causes of inflammation and mediates liver injury after HBV infection, we have discussed recent advances on the roles of various cytokines [including T helper type 1 cells (Th1), Th2, Th17, regulatory T cells (Treg)-related cytokines] in different phases of HBV infection and cytokine-related mechanisms for impaired viral control and liver damage during HBV infection. We then focus on experimental therapeutic applications of cytokines to gain a better understanding of this newly emerging aspect of disease pathogenesis.
72 citations
TL;DR: The duration of the response to both HBV and HAV vaccines is associated with suppression of the viral load at vaccination and, in the case of HBV vaccination, with a higher level of antibodies after vaccination.
Abstract: Hepatitis B and A account for considerable morbidity and mortality worldwide. Immunization is the most effective means of preventing hepatitis B and A. However, the immune response to both hepatitis vaccines seems to be reduced in HIV-infected subjects. The aim of this review was to analyze the immunogenicity, safety, long-term protection and current recommendations of hepatitis B and A vaccination among HIV-infected adults. The factors most frequently associated with a deficient level of anti-HBs or IgG anti-HAV after vaccination are those related to immunosuppression (CD4 level and HIV RNA viral load) and to the frequency of administration and/or the amount of antigenic load per dose. The duration of the response to both HBV and HAV vaccines is associated with suppression of the viral load at vaccination and, in the case of HBV vaccination, with a higher level of antibodies after vaccination. In terms of safety, there is no evidence of more, or different, adverse effects compared with HIV-free individuals. Despite literature-based advice on the administration of alternative schedules, revaccination after the failure of primary vaccination, and the need for periodic re-evaluation of antibody levels, few firm recommendations are found in the leading guidelines.
71 citations
TL;DR: It is shown that reinforced 40µg intramuscular HBV vaccination schedules are now frequently recommended, either initially in people never vaccinated, or in the lack of an anamnestic response in other situations.
Abstract: HBV immunization is highly recommended in people infected with HIV. However, the classical schedule used in the general population has been shown to be insufficient in people living with HIV. This ...
40 citations
Cites background from "GM-CSF Fails to Improve Immune Resp..."
...Numerous studies, from retrospective studies to randomized control trials (RCT), have found a correlation between undetectable HIV RNA, a high CD4 cell count and higher vaccination success.(19,20,23,27,30,60,63,75,93-97,100) The HIV viral load even seems to be more important than the CD4 count [19, 21, 23,], even though a positive correlation between the CD4 cell count at the time of (re)vaccination and the response to vaccination was observed in many studies....
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TL;DR: The necessity, timing and method of booster vaccination in responders with decreased anti-HBs responses, and effective vaccination against S-mutant HBV, are issues requiring resolution in the global prevention of HBV infection.
Abstract: Hepatitis B virus (HBV) infection is still a serious worldwide problem, and vaccination is the most effective strategy for primary prevention of the infection. Although universal vaccination may be required for total eradication, several countries, including Japan, have not yet adopted universal vaccination programs. Some individuals are non-responders to HBV vaccine and several mechanisms responsible for their poor response have been proposed. To overcome non-response, third generation vaccines with pre-S proteins have been developed. These vaccines have shown better anti-HBs responses and may also be effective in preventing infection by HBV with S mutant. Improvement of vaccine efficacy by intradermal administration, or co-administration with cytokines or adjuvants, may also be effective in non-responders. The necessity, timing and method of booster vaccination in responders with decreased anti-HBs responses, and effective vaccination against S-mutant HBV, are issues requiring resolution in the global prevention of HBV infection.
39 citations
References
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TL;DR: A 0-1-2 dose vaccination course with a booster dose administered at month 12, induces a protective immune response which lasts at least until 7 years after the full vaccination course of the subjects.
55 citations
"GM-CSF Fails to Improve Immune Resp..." refers background in this paper
...While vaccination with recombinant HBV vaccine yields durable protection in greater than 90% of vaccinated immunocompetent adults [11,12], HIV-infected persons respond poorly to vaccination with response rates ranging from 17 to 56% with standard HBV vaccination strategies [13-16]....
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TL;DR: This study suggests that GM-CSF increases the immunogenicity of recombinant HBV vaccine in HIV infected individuals.
52 citations
"GM-CSF Fails to Improve Immune Resp..." refers methods in this paper
...In this study, we elected to evaluate GM-CSF as an adjuvant given previous data suggesting its utility for vaccine responses in both dialysis patients and HIV-infected persons [21-23,36]....
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TL;DR: Overall, HBV vaccination was not associated with reduced risk of HBV infection in the cohort of HIV-infected individuals, however, the small subset of vaccinees with a positive vaccine response may have had reduced HBV infections risk, including chronic disease.
Abstract: Objective— To assess the association of HBV vaccination with risk of HBV infection among HIV-infected patients and HBV infection risk factors among vaccinees. Correspondence and reprints: Michael L. Landrum, M.D., Infectious Disease Service, Brooke Army Medical Center, 3851 Roger BrookeDr, MCHE-MDI, Fort Sam Houston, Texas 78234, Telephone: 210-916-2839, Fax: 210-916-2121, mlandrum@idcrp.org. Authorship contribution: Conception and Design: Landrum, Hullsiek, AganData acquisition: Landrum, Ganesan, Weintrob, Crum-Cianflone, Barthel, O’ConnellStatistical analysis: Hullsiek, Landrum, FiebergData analysis and Interpretation: Landrum, Hullsiek, Ganesan, Weintrob, Crum-Cianflone, Barthel, O’Connell, Fieberg, Chun, Marconi,Dolan, AganDrafting manuscript: Landrum, HullsiekCritical revision of the manuscript: Ganesan, Weintrob, Crum-Cianflone, Barthel, O’Connell, Fieberg, Chun, Marconi, Dolan, AganFinal approval of manuscript: Landrum, Hullsiek, Ganesan, Weintrob, Crum-Cianflone, Barthel, O’Connell, Fieberg, Chun, Marconi,Dolan, AganObtaining funding: Landrum, AganTechnical support: O’ConnellMembers of the Infectious Disease Clinical Research Program HIV Working Group:National Institute of Allergy and Infectious Diseases, Bethesda, MD: M. Polis, J. Powers, J. Metcalf, E. Tramont.Naval Medical Center, Portsmouth, VA: J. Maguire, V. Barthel, S. Patel.Naval Medical Center, San Diego, CA: B. Hale, N. Crum-Cianflone, M. Bavaro, H. Chun.National Naval Medical Center, Bethesda, MD: T. Whitman, A. Ganesan.San Antonio Military Medical Center, San Antonio, TX: V. Marconi, M. Landrum, J. Delmar, W. Bradley.Tripler Army Medical Center: T. Ferguson, A. Johnson.University of Minnesota, Minneapolis, MN: A. Lifson, K. Hullsiek, A. Fieberg.Uniformed Services University of the Health Sciences, Bethesda, MD: S. Wegner, B. Agan, G. Martin.Walter Reed Army Institute of Research, Silver Spring, MD: N. Michael, M. Milazzo, R. O’Connell, S. Peel.Walter Reed Army Medical Center, Washington, DC: G. Wortmann, C. Hawkes, A. Weintrob, S. Fraser.
47 citations
"GM-CSF Fails to Improve Immune Resp..." refers background in this paper
...Additionally, cases of confirmed HBV infection (HBsAg reactivity) have been reported among HIV-infected persons despite HBV vaccination [32-34]....
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TL;DR: Haemodialysis patients often fail to respond to hepatitis B vaccination, and being given 0.5, 5, 5 or 10μg kg‐1 granulocyte‐macrophage colony‐stimulating factor subcutaneously 24 h prior to booster vaccination with a hepatitis B vaccine was associated with adverse effects that were mild to moderate in severity and appeared to be dose dependent.
Abstract: Haemodialysis patients often fail to respond to hepatitis B vaccination. In this pilot study, 15 patients previously non-responsive to at least three 40 micrograms doses of hepatitis B vaccine were given 0.5, 5 or 10 micrograms kg-1 granulocyte-macrophage colony-stimulating factor (GM-CSF) subcutaneously 24 h prior to booster vaccination with a hepatitis B vaccine. Seven of the 15 patients developed antibody to hepatitis B surface antigen (HBsAb) (35-7240 IU L-1) upon initial vaccination with GM-CSF and two of four individuals responded with low HBsAb titres of 15 and 60 IU L-1 when revaccinated with hepatitis B surface antigen (HBsAg) and twice the dose of GM-CSF. The application of GM-CSF was associated with adverse effects that were, in general, mild to moderate in severity and appeared to be dose dependent. Two patients, both receiving 10 micrograms kg-1 GM-CSF discontinued the study because of severe hypotension.
46 citations
"GM-CSF Fails to Improve Immune Resp..." refers methods in this paper
...In this study, we elected to evaluate GM-CSF as an adjuvant given previous data suggesting its utility for vaccine responses in both dialysis patients and HIV-infected persons [21-23,36]....
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...another group of immunocompromised patients [22-24]....
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TL;DR: It is suggested that GM-CSF induced a significant effect in terms of response rate and achievement of an earlier seroconversion to the vaccine in the overall populations examined, in renal failure patients and in healthy individuals.
45 citations
"GM-CSF Fails to Improve Immune Resp..." refers methods in this paper
...In this study, we elected to evaluate GM-CSF as an adjuvant given previous data suggesting its utility for vaccine responses in both dialysis patients and HIV-infected persons [21-23,36]....
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...A meta-analysis of 13 studies evaluating GMCSF as an adjuvant for HBV vaccine yielded a 50% increase in the development of seroprotection after a single dose of vaccine and a 20% increase after the 3 dose series [21]....
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