Hepatitis C cross-genotype immunity and implications for vaccine development
While about a quarter of individuals clear their primary hepatitis C (HCV) infections spontaneously, clearance (spontaneous or treatment-induced) does not confer sterilizing immunity against a future infection. Since successful treatment does not prevent future infections either, an effective vaccin...
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| Veröffentlicht in: | Scientific reports 2017-09, Vol.7 (1), p.12326-8, Article 12326 |
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| creator | Islam, Nazrul Krajden, Mel Shoveller, Jean Gustafson, Paul Gilbert, Mark Wong, Jason Tyndall, Mark W. Janjua, Naveed Zafar |
| description | While about a quarter of individuals clear their primary hepatitis C (HCV) infections spontaneously, clearance (spontaneous or treatment-induced) does not confer sterilizing immunity against a future infection. Since successful treatment does not prevent future infections either, an effective vaccine is highly desirable in preventing HCV (re)infection. However, development of an effective vaccine has been complicated by the diversity of HCV genotypes, and complexities in HCV immunological responses. Smaller studies on humans and chimpanzees reported seemingly opposing results regarding cross-neutralizing antibodies. We report a lack of cross-genotype immunity in the largest cohort of people to date. In the adjusted Cox proportional hazards model, reinfection with a heterologous HCV genotype (adjusted Hazard Ratio [aHR]: 0.45, 95% CI: 0.25–0.84) was associated with a 55% lower likelihood of re-clearance. Among those who cleared their first infection spontaneously, the likelihood of re-clearance was 49% lower (aHR: 0.51, 95% CI: 0.27–0.94) when reinfected with a heterologous HCV genotype. These findings indicate that immunity against a particular HCV genotype does not offer expanded immunity to protect against subsequent infections with a different HCV genotype. A prophylactic HCV vaccine boosted with multiple HCV genotype may offer a broader and more effective protection. |
| doi_str_mv | 10.1038/s41598-017-10190-8 |
| format | Article |
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Since successful treatment does not prevent future infections either, an effective vaccine is highly desirable in preventing HCV (re)infection. However, development of an effective vaccine has been complicated by the diversity of HCV genotypes, and complexities in HCV immunological responses. Smaller studies on humans and chimpanzees reported seemingly opposing results regarding cross-neutralizing antibodies. We report a lack of cross-genotype immunity in the largest cohort of people to date. In the adjusted Cox proportional hazards model, reinfection with a heterologous HCV genotype (adjusted Hazard Ratio [aHR]: 0.45, 95% CI: 0.25–0.84) was associated with a 55% lower likelihood of re-clearance. Among those who cleared their first infection spontaneously, the likelihood of re-clearance was 49% lower (aHR: 0.51, 95% CI: 0.27–0.94) when reinfected with a heterologous HCV genotype. These findings indicate that immunity against a particular HCV genotype does not offer expanded immunity to protect against subsequent infections with a different HCV genotype. A prophylactic HCV vaccine boosted with multiple HCV genotype may offer a broader and more effective protection.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-017-10190-8</identifier><identifier>PMID: 28951612</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>692/308/174 ; 692/699/255/234/2513/1551 ; Adult ; Antibodies, Neutralizing - blood ; Antibodies, Neutralizing - immunology ; Cohort Studies ; Cross Protection - genetics ; Cross Protection - immunology ; Female ; Genotype ; Genotype & phenotype ; Genotypes ; Hepacivirus - genetics ; Hepacivirus - immunology ; Hepatitis ; Hepatitis C ; Hepatitis C - blood ; Hepatitis C - immunology ; Hepatitis C - prevention & control ; Hepatitis C - virology ; Hepatitis C Antibodies - blood ; Hepatitis C Antibodies - immunology ; Humanities and Social Sciences ; Humans ; Immunity ; Immunization, Secondary - methods ; Infections ; Male ; Middle Aged ; multidisciplinary ; Science ; Science (multidisciplinary) ; Treatment Outcome ; Vaccination - methods ; Vaccine development ; Vaccines ; Viral Envelope Proteins - genetics ; Viral Envelope Proteins - immunology ; Viral Hepatitis Vaccines - genetics ; Viral Hepatitis Vaccines - immunology ; Viral Hepatitis Vaccines - therapeutic use</subject><ispartof>Scientific reports, 2017-09, Vol.7 (1), p.12326-8, Article 12326</ispartof><rights>The Author(s) 2017</rights><rights>2017. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-63091b2a4bc3359d0477f777b7d6b76fcf463ebda015deda1f4ee0185c0617253</citedby><cites>FETCH-LOGICAL-c474t-63091b2a4bc3359d0477f777b7d6b76fcf463ebda015deda1f4ee0185c0617253</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5615075/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5615075/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,41096,42165,51551,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28951612$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Islam, Nazrul</creatorcontrib><creatorcontrib>Krajden, Mel</creatorcontrib><creatorcontrib>Shoveller, Jean</creatorcontrib><creatorcontrib>Gustafson, Paul</creatorcontrib><creatorcontrib>Gilbert, Mark</creatorcontrib><creatorcontrib>Wong, Jason</creatorcontrib><creatorcontrib>Tyndall, Mark W.</creatorcontrib><creatorcontrib>Janjua, Naveed Zafar</creatorcontrib><creatorcontrib>The BC-HTC Team</creatorcontrib><title>Hepatitis C cross-genotype immunity and implications for vaccine development</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>While about a quarter of individuals clear their primary hepatitis C (HCV) infections spontaneously, clearance (spontaneous or treatment-induced) does not confer sterilizing immunity against a future infection. Since successful treatment does not prevent future infections either, an effective vaccine is highly desirable in preventing HCV (re)infection. However, development of an effective vaccine has been complicated by the diversity of HCV genotypes, and complexities in HCV immunological responses. Smaller studies on humans and chimpanzees reported seemingly opposing results regarding cross-neutralizing antibodies. We report a lack of cross-genotype immunity in the largest cohort of people to date. In the adjusted Cox proportional hazards model, reinfection with a heterologous HCV genotype (adjusted Hazard Ratio [aHR]: 0.45, 95% CI: 0.25–0.84) was associated with a 55% lower likelihood of re-clearance. Among those who cleared their first infection spontaneously, the likelihood of re-clearance was 49% lower (aHR: 0.51, 95% CI: 0.27–0.94) when reinfected with a heterologous HCV genotype. These findings indicate that immunity against a particular HCV genotype does not offer expanded immunity to protect against subsequent infections with a different HCV genotype. A prophylactic HCV vaccine boosted with multiple HCV genotype may offer a broader and more effective protection.</description><subject>692/308/174</subject><subject>692/699/255/234/2513/1551</subject><subject>Adult</subject><subject>Antibodies, Neutralizing - blood</subject><subject>Antibodies, Neutralizing - immunology</subject><subject>Cohort Studies</subject><subject>Cross Protection - genetics</subject><subject>Cross Protection - immunology</subject><subject>Female</subject><subject>Genotype</subject><subject>Genotype & phenotype</subject><subject>Genotypes</subject><subject>Hepacivirus - genetics</subject><subject>Hepacivirus - immunology</subject><subject>Hepatitis</subject><subject>Hepatitis C</subject><subject>Hepatitis C - blood</subject><subject>Hepatitis C - immunology</subject><subject>Hepatitis C - prevention & control</subject><subject>Hepatitis C - virology</subject><subject>Hepatitis C Antibodies - blood</subject><subject>Hepatitis C Antibodies - immunology</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>Immunity</subject><subject>Immunization, Secondary - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Islam, Nazrul</au><au>Krajden, Mel</au><au>Shoveller, Jean</au><au>Gustafson, Paul</au><au>Gilbert, Mark</au><au>Wong, Jason</au><au>Tyndall, Mark W.</au><au>Janjua, Naveed Zafar</au><aucorp>The BC-HTC Team</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Hepatitis C cross-genotype immunity and implications for vaccine development</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2017-09-26</date><risdate>2017</risdate><volume>7</volume><issue>1</issue><spage>12326</spage><epage>8</epage><pages>12326-8</pages><artnum>12326</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>While about a quarter of individuals clear their primary hepatitis C (HCV) infections spontaneously, clearance (spontaneous or treatment-induced) does not confer sterilizing immunity against a future infection. Since successful treatment does not prevent future infections either, an effective vaccine is highly desirable in preventing HCV (re)infection. However, development of an effective vaccine has been complicated by the diversity of HCV genotypes, and complexities in HCV immunological responses. Smaller studies on humans and chimpanzees reported seemingly opposing results regarding cross-neutralizing antibodies. We report a lack of cross-genotype immunity in the largest cohort of people to date. In the adjusted Cox proportional hazards model, reinfection with a heterologous HCV genotype (adjusted Hazard Ratio [aHR]: 0.45, 95% CI: 0.25–0.84) was associated with a 55% lower likelihood of re-clearance. Among those who cleared their first infection spontaneously, the likelihood of re-clearance was 49% lower (aHR: 0.51, 95% CI: 0.27–0.94) when reinfected with a heterologous HCV genotype. These findings indicate that immunity against a particular HCV genotype does not offer expanded immunity to protect against subsequent infections with a different HCV genotype. A prophylactic HCV vaccine boosted with multiple HCV genotype may offer a broader and more effective protection.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>28951612</pmid><doi>10.1038/s41598-017-10190-8</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 692/308/174 692/699/255/234/2513/1551 Adult Antibodies, Neutralizing - blood Antibodies, Neutralizing - immunology Cohort Studies Cross Protection - genetics Cross Protection - immunology Female Genotype Genotype & phenotype Genotypes Hepacivirus - genetics Hepacivirus - immunology Hepatitis Hepatitis C Hepatitis C - blood Hepatitis C - immunology Hepatitis C - prevention & control Hepatitis C - virology Hepatitis C Antibodies - blood Hepatitis C Antibodies - immunology Humanities and Social Sciences Humans Immunity Immunization, Secondary - methods Infections Male Middle Aged multidisciplinary Science Science (multidisciplinary) Treatment Outcome Vaccination - methods Vaccine development Vaccines Viral Envelope Proteins - genetics Viral Envelope Proteins - immunology Viral Hepatitis Vaccines - genetics Viral Hepatitis Vaccines - immunology Viral Hepatitis Vaccines - therapeutic use |
| title | Hepatitis C cross-genotype immunity and implications for vaccine development |
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