Publication Date:
2008-05-02
Description:
Pre-existing neutralizing antibody provides the first line of defence against pathogens in general. For influenza virus, annual vaccinations are given to maintain protective levels of antibody against the currently circulating strains. Here we report that after booster vaccination there was a rapid and robust influenza-specific IgG+ antibody-secreting plasma cell (ASC) response that peaked at approximately day 7 and accounted for up to 6% of peripheral blood B cells. These ASCs could be distinguished from influenza-specific IgG+ memory B cells that peaked 14-21 days after vaccination and averaged 1% of all B cells. Importantly, as much as 80% of ASCs purified at the peak of the response were influenza specific. This ASC response was characterized by a highly restricted B-cell receptor (BCR) repertoire that in some donors was dominated by only a few B-cell clones. This pauci-clonal response, however, showed extensive intraclonal diversification from accumulated somatic mutations. We used the immunoglobulin variable regions isolated from sorted single ASCs to produce over 50 human monoclonal antibodies (mAbs) that bound to the three influenza vaccine strains with high affinity. This strategy demonstrates that we can generate multiple high-affinity mAbs from humans within a month after vaccination. The panel of influenza-virus-specific human mAbs allowed us to address the issue of original antigenic sin (OAS): the phenomenon where the induced antibody shows higher affinity to a previously encountered influenza virus strain compared with the virus strain present in the vaccine. However, we found that most of the influenza-virus-specific mAbs showed the highest affinity for the current vaccine strain. Thus, OAS does not seem to be a common occurrence in normal, healthy adults receiving influenza vaccination.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2515609/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2515609/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wrammert, Jens -- Smith, Kenneth -- Miller, Joe -- Langley, William A -- Kokko, Kenneth -- Larsen, Christian -- Zheng, Nai-Ying -- Mays, Israel -- Garman, Lori -- Helms, Christina -- James, Judith -- Air, Gillian M -- Capra, J Donald -- Ahmed, Rafi -- Wilson, Patrick C -- HHSN266200500026C/PHS HHS/ -- HHSN266200700006C/PHS HHS/ -- N01-AI-50025-02/AI/NIAID NIH HHS/ -- P20 RR018758/RR/NCRR NIH HHS/ -- P20 RR018758-057588/RR/NCRR NIH HHS/ -- P30 AR053483/AR/NIAMS NIH HHS/ -- R01 AI050933/AI/NIAID NIH HHS/ -- U19 AI057266/AI/NIAID NIH HHS/ -- U19 AI057266-04/AI/NIAID NIH HHS/ -- U19-AI057266-04/AI/NIAID NIH HHS/ -- UL1 TR000454/TR/NCATS NIH HHS/ -- England -- Nature. 2008 May 29;453(7195):667-71. doi: 10.1038/nature06890. Epub 2008 Apr 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18449194" target="_blank"〉PubMed〈/a〉
Keywords:
Antibodies, Monoclonal/*biosynthesis/genetics/*immunology
;
Antibody Affinity/*immunology
;
Antibody Specificity/immunology
;
Clone Cells/immunology/metabolism
;
Cloning, Molecular
;
Humans
;
Immunization, Secondary
;
Immunoglobulin G/genetics/immunology
;
Immunologic Memory/*immunology
;
Influenza A Virus, H1N1 Subtype/immunology
;
Influenza A Virus, H3N2 Subtype/immunology
;
Influenza B virus/immunology
;
Influenza Vaccines/immunology
;
Models, Immunological
;
Orthomyxoviridae/*immunology
;
Plasma Cells/immunology/metabolism
;
Somatic Hypermutation, Immunoglobulin/genetics
;
Time Factors
;
Vaccination
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
