Hookworms infect more that 400 million people and cause significant socio-economic burden on endemic countries. The lack of efficient vaccines and the emergence of anthelminthic drug resistance are of major concern. Free-living hookworm larvae infect their hosts via the skin and live as adult worms in the small intestine where they feed on host tissue and blood. Excretory/secretory (E/S) products, released by helminths as they migrate through their host, are thought to play a key role in facilitating infection and successful establishment of parasitism. However, E/S products can also elicit protective immune responses that might be harnessed for vaccine development. By performing Western blots with serum of Nippostrongylus brasiliensis (Nb) infected mice as a model for human hookworm infection, we identified a largely overlapping set of IgG1- and IgE-reactive antigens in E/S from infective L3 stage larvae. Mass spectrometry analysis led to the identification of a new protein family with 6 paralogues in the Nb genome which we termed Nb-LSA1 for "Nippostrongylus brasiliensis larval secreted protein 1". The recombinantly expressed 17 kDa family member Nb-LSA1a was recognized by antibodies in the serum of Nb immune mice. Immunization of mice with Nb-LSA1a in alum elicited a strong IgG1 response but no detectable antigen-specific IgE. Most importantly, immunized mice were largely protected against a challenge Nb infection. This effect was dependent on the presence of basophils and occurred before the parasites reached the intestine. Therefore, basophils appear to play a critical role for rapid control of infection with L3 stage larvae in mice immunized with a single secreted larval protein. A better understanding of basophil-mediated protective immunity and identification of potent larval antigens of human hookworms could help to develop promising vaccination strategies.
%0 Journal Article
%1 thumaNewlyIdentifiedSecreted2022
%A Thuma, Natalie
%A Döhler, Daniela
%A Mielenz, Dirk
%A Sticht, Heinrich
%A Radtke, Daniel
%A Reimann, Lena
%A Warscheid, Bettina
%A Voehringer, David
%C Switzerland
%D 2022
%J Frontiers in immunology
%K *Antigens E,Immunoglobulin G,Larva,Mice,Nippostrongylus,SCP/TAPS Helminth,*Basophils,Ancylostomatoidea,Animals,basophils,CAP domain,hookworms,Humans,immunization,Immunoglobulin protein,to_read
%P 979491
%R 10.3389/fimmu.2022.979491
%T A Newly Identified Secreted Larval Antigen Elicits Basophil-Dependent Protective Immunity against N. Brasiliensis Infection.
%V 13
%X Hookworms infect more that 400 million people and cause significant socio-economic burden on endemic countries. The lack of efficient vaccines and the emergence of anthelminthic drug resistance are of major concern. Free-living hookworm larvae infect their hosts via the skin and live as adult worms in the small intestine where they feed on host tissue and blood. Excretory/secretory (E/S) products, released by helminths as they migrate through their host, are thought to play a key role in facilitating infection and successful establishment of parasitism. However, E/S products can also elicit protective immune responses that might be harnessed for vaccine development. By performing Western blots with serum of Nippostrongylus brasiliensis (Nb) infected mice as a model for human hookworm infection, we identified a largely overlapping set of IgG1- and IgE-reactive antigens in E/S from infective L3 stage larvae. Mass spectrometry analysis led to the identification of a new protein family with 6 paralogues in the Nb genome which we termed Nb-LSA1 for "Nippostrongylus brasiliensis larval secreted protein 1". The recombinantly expressed 17 kDa family member Nb-LSA1a was recognized by antibodies in the serum of Nb immune mice. Immunization of mice with Nb-LSA1a in alum elicited a strong IgG1 response but no detectable antigen-specific IgE. Most importantly, immunized mice were largely protected against a challenge Nb infection. This effect was dependent on the presence of basophils and occurred before the parasites reached the intestine. Therefore, basophils appear to play a critical role for rapid control of infection with L3 stage larvae in mice immunized with a single secreted larval protein. A better understanding of basophil-mediated protective immunity and identification of potent larval antigens of human hookworms could help to develop promising vaccination strategies.
@article{thumaNewlyIdentifiedSecreted2022,
abstract = {Hookworms infect more that 400 million people and cause significant socio-economic burden on endemic countries. The lack of efficient vaccines and the emergence of anthelminthic drug resistance are of major concern. Free-living hookworm larvae infect their hosts via the skin and live as adult worms in the small intestine where they feed on host tissue and blood. Excretory/secretory (E/S) products, released by helminths as they migrate through their host, are thought to play a key role in facilitating infection and successful establishment of parasitism. However, E/S products can also elicit protective immune responses that might be harnessed for vaccine development. By performing Western blots with serum of Nippostrongylus brasiliensis (Nb) infected mice as a model for human hookworm infection, we identified a largely overlapping set of IgG1- and IgE-reactive antigens in E/S from infective L3 stage larvae. Mass spectrometry analysis led to the identification of a new protein family with 6 paralogues in the Nb genome which we termed Nb-LSA1 for "Nippostrongylus brasiliensis larval secreted protein 1". The recombinantly expressed 17 kDa family member Nb-LSA1a was recognized by antibodies in the serum of Nb immune mice. Immunization of mice with Nb-LSA1a in alum elicited a strong IgG1 response but no detectable antigen-specific IgE. Most importantly, immunized mice were largely protected against a challenge Nb infection. This effect was dependent on the presence of basophils and occurred before the parasites reached the intestine. Therefore, basophils appear to play a critical role for rapid control of infection with L3 stage larvae in mice immunized with a single secreted larval protein. A better understanding of basophil-mediated protective immunity and identification of potent larval antigens of human hookworms could help to develop promising vaccination strategies.},
added-at = {2024-05-17T13:01:35.000+0200},
address = {Switzerland},
author = {Thuma, Natalie and D{\"o}hler, Daniela and Mielenz, Dirk and Sticht, Heinrich and Radtke, Daniel and Reimann, Lena and Warscheid, Bettina and Voehringer, David},
biburl = {https://www.bibsonomy.org/bibtex/255081c459dadb4809608bb076d1cb19d/warscheidlab},
copyright = {Copyright {\copyright} 2022 Thuma, D{\"o}hler, Mielenz, Sticht, Radtke, Reimann, Warscheid and Voehringer.},
doi = {10.3389/fimmu.2022.979491},
interhash = {54871833a41aeb54bbbe291ee9eb35e2},
intrahash = {55081c459dadb4809608bb076d1cb19d},
issn = {1664-3224},
journal = {Frontiers in immunology},
keywords = {*Antigens E,Immunoglobulin G,Larva,Mice,Nippostrongylus,SCP/TAPS Helminth,*Basophils,Ancylostomatoidea,Animals,basophils,CAP domain,hookworms,Humans,immunization,Immunoglobulin protein,to_read},
langid = {english},
pages = 979491,
pmcid = {PMC9453252},
pmid = {36091065},
timestamp = {2024-05-17T13:01:35.000+0200},
title = {A Newly Identified Secreted Larval Antigen Elicits Basophil-Dependent Protective Immunity against {{N}}. Brasiliensis Infection.},
volume = 13,
year = 2022
}