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Hepatitis B vaccination in relatives to known non-responders: A family study
Linköpings universitet, Institutionen för klinisk och experimentell medicin, Infektionsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Infektionskliniken US.
Linköpings universitet, Institutionen för klinisk och experimentell medicin, Rättsmedicin. Linköpings universitet, Hälsouniversitetet.
Linköpings universitet, Institutionen för klinisk och experimentell medicin, Infektionsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Infektionskliniken US.
(engelsk)Manuskript (Annet vitenskapelig)
Abstract [en]

Hepatitis B can be prevented by hepatitis B vaccine in most individuals. However about 5 –10% of all individuals fail to produce a protective antibody level to hepatitis B surface antigen(anti-HBs), after standard vaccination procedure with three vaccine doses. The mechanismsfor non-response are multi-factorial and not clearly understood. Non-response in this studywas defined as anti-HBs < 10 mIU/ml after at least 4 doses of intradermal hepatitis B vaccine.In this study we vaccinated relatives to known non-responders to hepatitis B vaccine. Thestudy subjects were chosen among relatives to non-responders with known HLA class IIhaplotypes. Recombinant hepatitis B vaccine was administered intradermally at 0, 1 and 6months. For those with anti-HBs <10 mIU/ml after three doses an additional dose was givenfollowed by new anti-HBs measurement. A total of 8 probands and 26 relatives wereincluded. Of the 26 relatives 15/26 (58%) responded to the vaccination schedule compared tothe expected 90-95%. This data therefore support the theory that genetic factors play animportant role in the antibody response to hepatitis B vaccine. The study population wasthough too small to conclude the role of specific genetic factors related to response and nonresponse.

Emneord [en]
Hepatitis B vaccine, non-responders, genetics
HSV kategori
Identifikatorer
URN: urn:nbn:se:liu:diva-20798OAI: oai:DiVA.org:liu-20798DiVA, id: diva2:236071
Tilgjengelig fra: 2009-09-21 Laget: 2009-09-21 Sist oppdatert: 2010-01-14bibliografisk kontrollert
Inngår i avhandling
1. Studies on Hepatitis B Vaccination and Factors Associated withthe Vaccine Response
Åpne denne publikasjonen i ny fane eller vindu >>Studies on Hepatitis B Vaccination and Factors Associated withthe Vaccine Response
2009 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
Abstract [en]

Hepatitis B virus causes liver disease and up to 2 billion people have been in contact with the virus world wide. It can cause both acute and chronic disease. The routes for transmission are through blood, mother to infant at time of delivery and sexually. Chronic hepatitis B infection is a risk factor for development of liver cirrhosis and hepatocellular carcinoma. Prevention of hepatitis B virus infection is highly desirable. Since the early1980s hepatitis B vaccine has been available. It can effectively prevent the disease and has been found to be safe. The World Health Organisation, WHO, has recommended all countries to implement the vaccine in their children’s vaccination programmes and many countries have followed this recommendation. In Sweden so far the recommendation is vaccination of identified risk groups for hepatitis B. Health care workers who are at risk of having blood contact in their work is one such risk group.

In a large study on health care workers who were intradermally vaccinated with the hepatitis B vaccine, 960/1406 (68.3%) developed protective levels of antibodies to HBsAg (anti-HBs; defined as >10 mIU/mL) after three doses. After administering of an additional fourth dose to non-responders the response rate was 1187/1335 (88.9%). Risk factors for non-response were smoking and age above 40 years. Also, the vaccine response rates improved during the study and a risk of giving a too small dose with intradermal administration was also identified. This suggests that intradermal administration is dependent on well trained personnel.

A genetic factor which has been proposed to be associated with a non-responder status to HBV vaccination is the HLA haplotype of the host. In a study in on 69 responders and 53 non-responders the haplotypes were therefore determined. It was found that [DQB1*0602; DQA1*0102; DR15] and [DQB1*0603; DQA1*0103; DRB1*1301] were more likely to be found in responders (p<0.025 and p<0.05 respectively). In non-responders the haplotype [DQB1*0604; DQA1*0102; DRB1*1302] was found more frequently (p<0.005). This study supports that the HLA class II of the host is involved in the ability to respond to the HBV vaccination.

To further test the genetic link between the HLA of the host and a non-responder status, relatives to known intradermal non-responders with known haplotypes for DQA1, DQB1 and DRB1 were vaccinated in the same way, intradermally. The response rate in the relatives was 15/26 (58%) which is lower than expected suggesting a genetic influence on the vaccine response. In this study 5/6 with the haplotype [DQB1*0604; DQA1*0102; DRB1*1302] were non-responders which is in line with the previous data that this haplotype is correlated to hepatitis B vaccine non-response.

Finally, to test a strategy by which we could induce an effective anti-HBs seroconversion in non-responders we revaccinated these with the combined hepatitis A and B vaccine intramuscularly at a double dose. Already after the first revaccination dose 26/44 (60%) responded with protective antibodies compared to 2/20 (10%) in a vaccine naïve reference group, suggesting an anamnestic response. After three doses 42/44 (95%) responded in the non-responder group and 20/20 (100%) in the reference group. All participants in the study responded to the hepatitis A antigen.

In conclusion these studies show that intradermal vaccine administration can be used and is effective, and that the ability to respond is influenced by several, including genetic, factors. Importantly a non-responder status to hepatitis B vaccination is not absolute, a double dose of the combined HAV and HBV vaccine effectively overcomes this non-response in most individuals.

sted, utgiver, år, opplag, sider
Linköping: Linköping University Electronic Press, 2009. s. 67
Serie
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1127
HSV kategori
Identifikatorer
urn:nbn:se:liu:diva-20800 (URN)978-91-7393-634-7 (ISBN)
Disputas
2009-10-20, Elsa Brändströmsalen, Hälsouniversitetet, Campus US, Linköpings Universitet, Linköping, 13:00 (svensk)
Opponent
Veileder
Tilgjengelig fra: 2009-09-21 Laget: 2009-09-21 Sist oppdatert: 2012-05-09bibliografisk kontrollert

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