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Review

Subdominance in Antibody Responses: Implications for Vaccine Development

Gunnar Lindahl
Gunnar Lindahl
aDepartment of Chemistry, Division of Applied Microbiology, Lund University, Lund, Sweden
bDepartment of Laboratory Medicine, Division of Medical Microbiology, Lund University, Lund, Sweden
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DOI: 10.1128/MMBR.00078-20
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SUMMARY

Vaccines work primarily by eliciting antibodies, even when recovery from natural infection depends on cellular immunity. Large efforts have therefore been made to identify microbial antigens that elicit protective antibodies, but these endeavors have encountered major difficulties, as witnessed by the lack of vaccines against many pathogens. This review summarizes accumulating evidence that subdominant protein regions, i.e., surface-exposed regions that elicit relatively weak antibody responses, are of particular interest for vaccine development. This concept may seem counterintuitive, but subdominance may represent an immune evasion mechanism, implying that the corresponding region potentially is a key target for protective immunity. Following a presentation of the concepts of immunodominance and subdominance, the review will present work on subdominant regions in several major human pathogens: the protozoan Plasmodium falciparum, two species of pathogenic streptococci, and the dengue and influenza viruses. Later sections are devoted to the molecular basis of subdominance, its potential role in immune evasion, and general implications for vaccine development. Special emphasis will be placed on the fact that a whole surface-exposed protein domain can be subdominant, as demonstrated for all of the pathogens described here. Overall, the available data indicate that subdominant protein regions are of much interest for vaccine development, not least in bacterial and protozoal systems, for which antibody subdominance remains largely unexplored.

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Subdominance in Antibody Responses: Implications for Vaccine Development
Gunnar Lindahl
Microbiology and Molecular Biology Reviews Nov 2020, 85 (1) e00078-20; DOI: 10.1128/MMBR.00078-20

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Subdominance in Antibody Responses: Implications for Vaccine Development
Gunnar Lindahl
Microbiology and Molecular Biology Reviews Nov 2020, 85 (1) e00078-20; DOI: 10.1128/MMBR.00078-20
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  • Top
  • Article
    • SUMMARY
    • INTRODUCTION
    • IMMUNODOMINANCE AND SUBDOMINANCE IN ANTIBODY RESPONSES
    • PLASMODIUM FALCIPARUM: THE CS PROTEIN
    • STREPTOCOCCAL SURFACE PROTEINS
    • DENGUE VIRUS: THE E PROTEIN
    • INFLUENZA VIRUS: HEMAGGLUTININ
    • MOLECULAR BASIS OF ANTIBODY SUBDOMINANCE
    • IS SUBDOMINANCE A MECHANISM OF IMMUNE ESCAPE?
    • SUBDOMINANCE AND VACCINE DEVELOPMENT: GENERAL COMMENTS
    • CONCLUDING REMARKS
    • ACKNOWLEDGMENTS
    • REFERENCES
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KEYWORDS

immune escape
Plasmodium falciparum
Streptococcus agalactiae
Streptococcus pyogenes
antibodies
Dengue Virus
immunodominance
influenza virus
subdominance
vaccine

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