liu.seSearch for publications in DiVA
Endre søk
RefereraExporteraLink to record
Permanent link

Direct link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Haplotypes comprising subtypes of the DQB1*06 allele direct the antibody response after immunisation with hepatitis B surface antigen
Linköpings universitet, Institutionen för klinisk och experimentell medicin, Infektionsmedicin. Linköpings universitet, Hälsouniversitetet.
Linköpings universitet, Institutionen för klinisk och experimentell medicin, Infektionsmedicin. Linköpings universitet, Hälsouniversitetet.
Linköpings universitet, Institutionen för klinisk och experimentell medicin, Infektionsmedicin. Linköpings universitet, Hälsouniversitetet.
1998 (engelsk)Inngår i: Tissue Antigens, ISSN 0001-2815, E-ISSN 1399-0039, Vol. 52, nr 4, s. 374-380Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Two HLA class II haplotypes, HLA-[DQB1*0602; DQA1*0102; DR15] and HLA-[DQB1*0603; DQA1*0103; DRB1*1301] were found to be less common in 52 nonresponders compared with 68 responders, P<0.025 and P<0.05 respectively, after vaccination with hepatitis B surface antigen (HBsAg). Another haplotype, HLA-[DQB1*0604; DQA1*0102; DRB1*1302], had a significantly higher frequency in the nonresponders (P<0.005). The nonresponders and responders were nonsmoking, healthy individuals with an antibody concentration of <10 IU/l and >100 IU/l respectively. The three haplotypes comprise either of three different DQB1*06 subtypes. Two of the seven amino acids that differ between the two responder alleles DQB1*0602 and *0603 and the nonresponder allele *0604 are located in the peptide-binding groove of the DQB1 molecule. In addition to this finding, amino acid 86 in the DRB1 molecule seems to determine the response against HBsAg. DRB1*1301 and DR15 in the responder haplotypes have a Val at this position while the nonresponder haplotype has a Gly. These results suggest a role for both the DQB1*06 alleles and the DRB1 alleles *1301, *1302 and DR15 to direct either a response or a nonresponse against HBsAg. Sixteen HLA class II genotypes were found to be shared by 25 nonresponders and 32 responders. This finding of HLA-identical nonresponders and responders indicates an influence of other genetic factors in addition to the HLA system in the response to HBsAg.

sted, utgiver, år, opplag, sider
1998. Vol. 52, nr 4, s. 374-380
Emneord [en]
Frequency, haplotype, HIA class II, nonresponders, nonsmoking, responders
HSV kategori
Identifikatorer
URN: urn:nbn:se:liu:diva-20797DOI: 10.1111/j.1399-0039.1998.tb03058.xPubMedID: 9820601OAI: oai:DiVA.org:liu-20797DiVA, id: diva2:236068
Tilgjengelig fra: 2009-09-21 Laget: 2009-09-21 Sist oppdatert: 2017-12-13bibliografisk 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

Open Access i DiVA

Fulltekst mangler i DiVA

Andre lenker

Forlagets fulltekstPubMedLink to Ph.D. Thesis

Personposter BETA

Cardell, KristinaLindblom, Bertil

Søk i DiVA

Av forfatter/redaktør
Cardell, KristinaLindblom, Bertil
Av organisasjonen
I samme tidsskrift
Tissue Antigens

Søk utenfor DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric

doi
pubmed
urn-nbn
Totalt: 125 treff
RefereraExporteraLink to record
Permanent link

Direct link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf