Immunogenicity of the Hepatitis B Vaccine

Study Overview
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Brief Summary
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More than five decades have passed since the identification of the etiologic agent of hepatitis B and yet this infection is a challenge for public health worldwide. The development and availability of the first hepatitis B vaccines, still in the 1980s, was a milestone for the prevention of the hepatitis B virus, and currently known as the gold standard strategy for the elimination of this infectious disease. In several countries, the introduction of the immunobiological occurred gradually, by age groups and risk groups, and in general, started with newborns and children. This universal immunization strategy has contributed to reducing the incidence and changing the epidemiological profile of HBV worldwide. At the beginning of the 21st century, it was already possible to shift the epidemiological curve of the infection to parasitize with 50 years or more. On the other hand, despite vaccination against hepatitis B being the most assertive tool for the prevention of HBV, the low performance of the vaccine in older groups remains a challenge for public health and the object of this study. To our knowledge, there are no data showing the efficacy of doses of enhanced hepatitis B vaccines for older adults, and the purpose of this study is to investigate and compare the immunogenicity of the hepatitis B vaccine in adult adults aged 50 years and over, using conventional doses (20μg) versus (vs) booster doses.

Detailed Description
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More than five decades have passed since the identification of the etiologic agent of hepatitis B and yet this infection is a challenge for public health worldwide. The development and availability of the first hepatitis B vaccines, still in the 1980s, was a milestone for the prevention of the hepatitis B virus, and currently known as the gold standard strategy for the elimination of this infectious disease. In several countries, the introduction of the immunobiological occurred gradually, by age groups and risk groups, and in general, started with newborns and children. In Brazil, only in 2015, a free offer of the hepatitis B vaccine expanded a population aged 50 years or older. This universal immunization strategy has contributed to reducing the incidence and changing the epidemiological profile of HBV worldwide. At the beginning of the 21st century, it was already possible to shift the epidemiological curve of the infection to parasitize with 50 years or more. Consider this scenario of vulnerability to HBV in older adults, it is important to highlight some aspects. The increase in life expectancy around the world is real data and must be evaluated. In addition, contemporary aging is accompanied by an increase and improvement in sexual performance, overcoming myths about asexual old age and outdated stereotypes about sexuality for an adult population in the middle and late stages. On the other hand, sexual risk behavior in older people being observed, including unprotected sexual intercourse, multiple sexual partnerships, sexual intercourse with a sex worker, among others. Studies have been increasing the high prevalence of Sexually Transmitted Infections, especially hepatitis B in the elderly. Given this situation, hepatitis B vaccination is the most assertive tool for preventing HBV. However, even in countries that expand the offer of the vaccine to the entire population, poor performance of the hepatitis B vaccine in older groups remains a challenge for public health and is the object of this study. A study conducted by Meeren and collaborators, characterized the relationship age vs. age. vaccine response to hepatitis B in immunocompetent adults. The protection index identified, considering all age groups, was 94.5%. However, there was a continuous reduction in seroprotection associated with age, ranging from 98.6% for young adults aged 20-24 years to 64.8% for the elderly (≥65 years). In addition, this study suggested that the aging of the immune system starts in adulthood and is intensified after 50-60 years of age. In the United States, research conducted with competence aged ≥50 years, showed lower rates of seroconversion compared to younger people, with protection rates ranging from 68% to 82.2%. Another study carried out in this country, elucidated the risk of non-response to the anti-HBV vaccine in 63% for products ≥40 years old (p = 0.046). Finally, in Brazil, an investigation conducted by Caetano et al. with settlers in Goiás, also illustrated a low responsiveness to the hepatitis B vaccine in the older population. In the age group aged 40-49 years, seroprotection was identified in only 61.9% of the participants, and for the age group aged 50-59 years the rate of seroresponse was even lower, only 55.9% protective titles of anti- HBs. Another study with this same population in Mato Grosso do Sul, showed an average age above 40 years for our non-responders. Thus, the program that supplants this limitation is necessary, until the cohort of children immunized at birth from a late adulthood. The use of third generation vaccines for this population seems to be difficult to implement due to the high cost of this immunogen. In this way, more frequent or more concentrated doses of the second generation vaccine can be a safe alternative for the older population. To our knowledge, there are no data showing the efficacy of doses of enhanced hepatitis B vaccines for older adults, and the purpose of this study is to investigate and compare the immunogenicity of the hepatitis B vaccine in adult adults aged 50 years and over, using conventional doses (20μg) versus (vs) booster doses.

Official Title
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Immunogenicity of the Hepatitis B Vaccine in Individuals 50 Years Old or More: Randomized Clinical Trial

Conditions
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Vaccine Response Impaired, Hepatitis B, Aging

Intervention / Treatment
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* Biological: Standard vaccination schedule
* Biological: Reinforced vaccination schedule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: person is 50 years of age or older. Exclusion Criteria: people with chronic renal failure, cancer and HIV / AIDS, using corticosteroids; people with a history of hepatitis B vaccination (vaccination record of hepatitis B vaccine doses or previous report of hepatitis B vaccination); people who are positive for anti-HBs and / or total anti-HBc serological markers.

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The intervention group (Reinforced Intervention Scheme - EIR) indicates 3 doses of 40 μg (2 mL) of hepatitis B vaccine, in months 0, 1 and 6, while the comparison group (Conventional Comparison Scheme - ECC) completes 3 doses of 20 μg (1 mL) of the vaccine, in months 0, 1 and 6. To evaluate the kinetics of the hepatitis B vaccine, after each dose administered, about 30 to 60 days, 5 mL of blood was again collected from the participants for quantitative detection of anti-HBs, using the Microparticle Chemiluminescent Immunoassay (CMIA) method, according to the manufacturer's instructions.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Standard vaccination schedule<br>To evaluate the immunogenicity of the monovalent hepatitis B vaccine, expressed in Hansenula polymorpha, aged ≥50 years old, using a standard vaccination schedule (three doses of 20 μg, in months 0, 1, 6). | Biological: Standard vaccination schedule<br>* Administer a standard vaccination schedule (three doses of 20 μg of the hepatitis B vaccine, in months 0, 1, 6) at an age of ≥50 years and evaluate a production kinetics after each dose administered in the period of about 30 to 60 days.<br>|
| Experimental: Reinforced vaccination schedule<br>To evaluate the immunogenicity of the monovalent hepatitis B vaccine, expressed in Hansenula polymorpha, in individuals aged ≥50 years, using a reinforced vaccination schedule (three doses of 40 μg, in months 0, 1, 6). | Biological: Reinforced vaccination schedule<br>* Administer an enhanced vaccination schedule (three doses of 40 μg of the hepatitis B vaccine, in months 0, 1, 6) in individuals aged ≥50 years and assess the kinetics of antibody production after each dose administered in the period of approximately 30 to 60 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| More than 90% of the appropriate intervention sample of associated anti-HBs (≥10mUI / mL) after three doses of hepatitis B vaccine | Success of the proposed procedure, defined by the development of isolated anti-HBs titers (≥10mUI / mL) after three reinforced doses (40μg) of the hepatitis B vaccine, within 30 to 60 days after the end of the vaccination schedule. | Success of the proposed procedure, defined by the development of isolated anti-HBs titers (≥10mUI / mL) after three reinforced doses (40μg) of the hepatitis B vaccine, in 30 to 60 days after the end of the vaccination schedule. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| About 20-30% of the appropriate intervention sample of associated anti-HBs (≥10mUI / mL) after first dose of hepatitis B vaccine | Success of the proposed procedure, defined by the development of isolated anti-HBs titers (≥10mUI / mL) after one reinforced dose (40μg) of the hepatitis B vaccine, within 30 to 60 days after the end of the vaccination schedule. | Success of the proposed procedure, defined by the development of isolated anti-HBs titers (≥10mUI / mL) after one reinforced dose (40μg) of the hepatitis B vaccine, within 30 to 60 days after the end of the vaccination schedule. | 
| About 75-80% of the appropriate intervention sample of associated anti-HBs (≥10mUI / mL) after second dose of hepatitis B vaccine | Success of the proposed procedure, defined by the development of isolated anti-HBs titers (≥10mUI / mL) after two reinforced doses (40μg) of the hepatitis B vaccine, within 30 to 60 days after the end of the vaccination schedule. | Success of the proposed procedure, defined by the development of isolated anti-HBs titers (≥10mUI / mL) after two reinforced doses (40μg) of the hepatitis B vaccine, within 30 to 60 days after the end of the vaccination schedule. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vaccine Response Impaired, Hepatitis B, Aging