Subdominance in Antibody Responses : Implications for Vaccine Development
(2020) In Microbiology and Molecular Biology Reviews 85(1).- Abstract
SUMMARYVaccines 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... (More)
SUMMARYVaccines 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.
(Less)
- author
- Lindahl, Gunnar LU
- organization
- publishing date
- 2020
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- antibodies, dengue virus, immune escape, immunodominance, influenza virus, Plasmodium falciparum, Streptococcus agalactiae, Streptococcus pyogenes, subdominance, vaccine
- in
- Microbiology and Molecular Biology Reviews
- volume
- 85
- issue
- 1
- article number
- e00078-20
- publisher
- American Society for Microbiology
- external identifiers
-
- pmid:33239435
- scopus:85096818360
- ISSN
- 1092-2172
- DOI
- 10.1128/MMBR.00078-20
- language
- English
- LU publication?
- yes
- id
- 64229bd8-448c-4665-9b45-8eb57df97c8e
- date added to LUP
- 2020-12-11 10:05:28
- date last changed
- 2024-06-14 04:38:36
@article{64229bd8-448c-4665-9b45-8eb57df97c8e,
abstract = {{<p>SUMMARYVaccines 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.</p>}},
author = {{Lindahl, Gunnar}},
issn = {{1092-2172}},
keywords = {{antibodies; dengue virus; immune escape; immunodominance; influenza virus; Plasmodium falciparum; Streptococcus agalactiae; Streptococcus pyogenes; subdominance; vaccine}},
language = {{eng}},
number = {{1}},
publisher = {{American Society for Microbiology}},
series = {{Microbiology and Molecular Biology Reviews}},
title = {{Subdominance in Antibody Responses : Implications for Vaccine Development}},
url = {{http://dx.doi.org/10.1128/MMBR.00078-20}},
doi = {{10.1128/MMBR.00078-20}},
volume = {{85}},
year = {{2020}},
}