دورية أكاديمية
Greater Breadth of Vaccine-Induced Immunity in Females than Males Is Mediated by Increased Antibody Diversity in Germinal Center B Cells.
| العنوان: | Greater Breadth of Vaccine-Induced Immunity in Females than Males Is Mediated by Increased Antibody Diversity in Germinal Center B Cells. |
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| المؤلفون: | Ursin RL; Department of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA., Dhakal S; W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA., Liu H; W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA., Jayaraman S; Department of Pathology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA., Park HS; W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA., Powell HR; W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA., Sherer ML; W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA., Littlefield KE; W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA., Fink AL; W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA., Ma Z; W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA., Mueller AL; W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA., Chen AP; W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA., Seddu K; W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA., Woldetsadik YA; W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA., Gearhart PJ; Laboratory of Molecular Biology and Immunology, National Institute on Aginggrid.419475.a, National Institutes of Health, Baltimore, Maryland, USA., Larman HB; Department of Pathology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA., Maul RW; Laboratory of Molecular Biology and Immunology, National Institute on Aginggrid.419475.a, National Institutes of Health, Baltimore, Maryland, USA., Pekosz A; W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA., Klein SL; Department of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.; W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA. |
| المصدر: | MBio [mBio] 2022 Aug 30; Vol. 13 (4), pp. e0183922. Date of Electronic Publication: 2022 Jul 20. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Society for Microbiology Country of Publication: United States NLM ID: 101519231 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2150-7511 (Electronic) NLM ISO Abbreviation: mBio Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Washington, D.C. : American Society for Microbiology |
| مواضيع طبية MeSH: | Influenza A Virus, H1N1 Subtype*/genetics , Influenza Vaccines* , Influenza, Human* , Orthomyxoviridae Infections*, Animals ; Antibodies, Viral ; Antibody Diversity ; Epitopes ; Female ; Germinal Center ; Hemagglutinin Glycoproteins, Influenza Virus/genetics ; Hemagglutinins ; Humans ; Male ; Mice ; Vaccines, Inactivated |
| مستخلص: | Inactivated influenza vaccines induce greater antibody responses in females than males among both humans and mice. To test the breadth of protection, we used recombinant mouse-adapted A/California/2009 (maA/Cal/09) H1N1 viruses containing mutations at one (1M), two (2M), or three (3M) antigenic sites, in addition to a virus containing the 1M mutation and a substitution of the Ca2 antigenic site (Sub) with one derived from an H5 hemagglutinin (HA) to challenge mice of both sexes. Following maA/Cal/09 vaccination, females produced greater virus-specific, class-switched total IgG and IgG2c antibodies against the vaccine and all mutant viruses, and antibodies from females recognized a greater number of unique, linear HA epitopes than did antibodies from males. While females had greater neutralizing antibody titers against the vaccine virus, both sexes showed a lower neutralization capacity against mutant viruses. After virus challenge, vaccinated females had lower pulmonary virus titers and reduced morbidity than males for the 1M and 2M viruses, but not the Sub virus. Females generated greater numbers of germinal center (GC) B cells containing superior somatic hypermutation (SHM) frequencies than vaccinated males. Deletion of activation-induced cytidine deaminase ( Aicda ) eliminated female-biased immunity and protection against the 2M virus. Harnessing methods to improve GC B cell responses and frequencies of SHM, especially in males, should be considered in the development of universal influenza vaccines. IMPORTANCE Adult females develop greater antibody responses to influenza vaccines than males. We hypothesized that female-biased immunity and protection would be dependent on the extent of virus diversity as well as molecular mechanisms in B cells which constrain the breadth of epitope recognition. We developed a panel of mouse-adapted (ma) A/Cal/09 viruses that had mutations in the immunodominant hemagglutinin. Following vaccination against maA/Cal/09, females were better able to neutralize maA/Cal/09 than males, but neutralization of mutant maA/Cal/09 viruses was equally poor in both sexes, despite vaccinated females being better protected against these viruses. Vaccinated females benefited from the greater production of class-switched, somatically hypermutated antibodies generated in germinal center B cells, which increased recognition of more diverse maA/Cal/09 hemagglutinin antigen epitopes. Female-biased protection against influenza infection and disease after vaccination is driven by differential mechanisms in males versus females and should be considered in the design of novel vaccine platforms. |
| التعليقات: | Comment in: mBio. 2022 Oct 26;13(5):e0210622. (PMID: 36094090) |
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| معلومات مُعتمدة: | HHSN272201400007C United States AI NIAID NIH HHS; R25 GM109441 United States GM NIGMS NIH HHS; T32 GM136577 United States GM NIGMS NIH HHS; U54 AG062333 United States AG NIA NIH HHS |
| فهرسة مساهمة: | Keywords: H1N1; antibody function; antibody response; antigenic drift; antigenic variation; sex difference; viral immunity |
| المشرفين على المادة: | 0 (Antibodies, Viral) 0 (Epitopes) 0 (Hemagglutinin Glycoproteins, Influenza Virus) 0 (Hemagglutinins) 0 (Influenza Vaccines) 0 (Vaccines, Inactivated) |
| تواريخ الأحداث: | Date Created: 20220720 Date Completed: 20220902 Latest Revision: 20240214 |
| رمز التحديث: | 20240214 |
| مُعرف محوري في PubMed: | PMC9426573 |
| DOI: | 10.1128/mbio.01839-22 |
| PMID: | 35856618 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 2150-7511 |
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| DOI: | 10.1128/mbio.01839-22 |