Home LiteratureArticle Details
PMID: 11248804 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

C3d enhancement of antibodies to hemagglutinin accelerates protection against influenza virus challenge.

Nature immunology ·Vol. 1 ·No. 2 ·2000-08-00 ·Pages 127-31

Ross TM, Xu Y, Bright RA, Robinson HL

Abstract

The ability of the C3d component of complement to enhance antibody responses and protective immunity to influenza virus challenges was evaluated using a DNA vaccine encoding a C3d fusion of the hemagglutinin (HA) from influenza virus. Plasmids were generated that encoded a transmembrane HA (tmHA), a secreted form of HA (sHA), or a sHA fused to three tandem copies of the murine homologue of the C3d (sHA-3C3d). Analysis of the titers, avidity maturation, and hemagglutinin-inhibition activity of raised antibody revealed that immunizations with sHA-3C3d DNA accelerated both the avidity maturation of antibody to HA and the appearance of hemagglutinin-inhibition activity. These accelerated antibody responses correlated to a more rapid appearance of protective immunity. They also correlated to complete protection from live virus challenge by a single vaccination at a dose ten times lower than the protective dose for non-C3d forms of HA.

MeSH Terms
Animals Antibodies, Viral/biosynthesis,immunology Antibody Affinity Cell Line, Transformed Complement C3d/genetics,immunology Disease Models, Animal Gene Expression Hemagglutinin Glycoproteins, Influenza Virus/genetics,immunology Humans Influenza A virus/immunology Influenza Vaccines/genetics,immunology Influenza, Human/prevention & control Mice Mice, Inbred BALB C Plasmids Vaccines, DNA/genetics,immunology
Chemicals
Antibodies, Viral Hemagglutinin Glycoproteins, Influenza Virus Influenza Vaccines Vaccines, DNA Complement C3d
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Ross T M
Yerkes Regional Primate Research Center, Division of Microbiology and Immunology, Emory University, Atlanta, GA 30329, USA. RossT@mail.ecu.edu
Xu Y
Bright R A
Robinson H L
References (25)
25 references, click to expand
  1. The complement system and adaptive immunity.
    Semin Immunol. 1998 Oct;10(5):355-61 PMID: 9799710
  2. DNA vaccines.
    Dev Biol Stand. 1998;95:43-53 PMID: 9855413
  3. Studies on antibody responses following neonatal immunization with influenza hemagglutinin DNA or protein.
    Virology. 1999 May 10;257(2):406-14 PMID: 10329551
  4. DNA vaccines--designer vaccines for the 21st century.
    N Engl J Med. 1999 Jul 22;341(4):277-8 PMID: 10413742
  5. Replication of orthomyxoviruses.
    Adv Virus Res. 1999;54:319-48 PMID: 10547678
  6. Influenza vaccines: present and future.
    Adv Virus Res. 1999;54:349-73 PMID: 10547679
  7. DNA immunization: effect of secretion of DNA-expressed hemagglutinins on antibody responses.
    Vaccine. 1999 Dec 10;18(9-10):805-14 PMID: 10580193
  8. DNA vaccines for viral infections: basic studies and applications.
    Adv Virus Res. 2000;55:1-74 PMID: 11050940
  9. Dose-response relationship after immunization of volunteers with a new, surface-antigen-adsorbed influenza virus vaccine.
    J Infect Dis. 1977 Mar;135(3):423-31 PMID: 850080
  10. Construction of influenza haemagglutinin genes that code for intracellular and secreted forms of the protein.
    Nature. 1982 Dec 16;300(5893):598-603 PMID: 7144911
  11. Antibody avidity determination by ELISA using thiocyanate elution.
    J Immunol Methods. 1986 Jan 22;86(1):83-7 PMID: 3944471
  12. The roles of influenza virus haemagglutinin and nucleoprotein in protection: analysis using vaccinia virus recombinants.
    Scand J Immunol. 1987 Jan;25(1):21-8 PMID: 3492756
  13. A cloning cartridge of lambda t(o) terminator.
    Nucleic Acids Res. 1987 Apr 10;15(7):3185 PMID: 2951655
  14. Serological responses in volunteers to inactivated trivalent subunit influenza vaccine: antibody reactivity with epidemic influenza A and B strains and evidence of a rapid immune response.
    J Med Virol. 1991 Feb;33(2):133-7 PMID: 2051142
  15. Intraclonal generation of antibody mutants in germinal centres.
    Nature. 1991 Dec 5;354(6352):389-92 PMID: 1956400
  16. Maturation of the immune response in germinal centers.
    Cell. 1991 Dec 20;67(6):1121-9 PMID: 1760840
  17. Protection against a lethal influenza virus challenge by immunization with a haemagglutinin-expressing plasmid DNA.
    Vaccine. 1993;11(9):957-60 PMID: 8212843
  18. Heterologous and homologous protection against influenza A by DNA vaccination: optimization of DNA vectors.
    DNA Cell Biol. 1993 Nov;12(9):777-83 PMID: 8216848
  19. Accell particle-mediated DNA immunization elicits humoral, cytotoxic, and protective immune responses.
    AIDS Res Hum Retroviruses. 1994;10 Suppl 2:S43-5 PMID: 7865332
  20. The CD19/CR2/TAPA-1 complex of B lymphocytes: linking natural to acquired immunity.
    Annu Rev Immunol. 1995;13:127-49 PMID: 7542009
  21. C3d of complement as a molecular adjuvant: bridging innate and acquired immunity.
    Science. 1996 Jan 19;271(5247):348-50 PMID: 8553069
  22. Gene gun-based nucleic acid immunization: elicitation of humoral and cytotoxic T lymphocyte responses following epidermal delivery of nanogram quantities of DNA.
    Vaccine. 1995;13(15):1427-30 PMID: 8578820
  23. Disruption of the Cr2 locus results in a reduction in B-1a cells and in an impaired B cell response to T-dependent antigen.
    Immunity. 1996 Mar;4(3):251-62 PMID: 8624815
  24. Induction of protective immunity against influenza virus in a macaque model: comparison of conventional and iscom vaccines.
    J Gen Virol. 1997 Apr;78 ( Pt 4):757-65 PMID: 9129647
  25. DNA immunization for influenza virus: studies using hemagglutinin- and nucleoprotein-expressing DNAs.
    J Infect Dis. 1997 Aug;176 Suppl 1:S50-5 PMID: 9240695
Article Info
Journal
Nature immunology
Abbr.
Nat Immunol
ISSN
1529-2908
DOI
10.1038/77802
Email
rosst@mail.ecu.edu
Published
2000-08-00
Pages
127-31
Language
English
Region
United States
NLM ID
100941354
PMCID
PMC1635154
Subset
IM
Grants
NIA NIH HHS · R01 AG034946 · United States
NIAID NIH HHS · R01 AI34946 · United States
NIAID NIH HHS · R21 AI044325-02 · United States
NIAID NIH HHS · R21 AI44325 · United States
Corrections
CommentIn
PMID: 11248799
External Links
PubMed source DOI: 10.1038/77802 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2