IgG Responses to Porins and Lipopolysaccharide within an Outer Membrane-Based Vaccine against Nontyphoidal Develop at Discordant Rates

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IgG Responses to Porins and Lipopolysaccharide within an Outer Membrane-Based Vaccine against Nontyphoidal Develop at Discordant Rates. / Schager, Anna; Dominguez-Medina, Carmen C.; Necchi, Francesca ; Micoli, Francesca; Goh, Yun Shan; Goodall, Margaret; Flores-Langarica, Adriana; Bobat, Saeeda; Cook, Charlotte; Arcuri, Melissa; Marini, Arianna; King, Lloyd David William; Morris, Faye; Anderson, Graham; Toellner, Kai-Michael; Henderson, Ian; López-Macías, Constantino; MacLennan, Calman A. ; Cunningham, Adam.

In: mBio, Vol. 9, No. 2, e02379-17, 06.03.2018.

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Schager, Anna ; Dominguez-Medina, Carmen C. ; Necchi, Francesca ; Micoli, Francesca ; Goh, Yun Shan ; Goodall, Margaret ; Flores-Langarica, Adriana ; Bobat, Saeeda ; Cook, Charlotte ; Arcuri, Melissa ; Marini, Arianna ; King, Lloyd David William ; Morris, Faye ; Anderson, Graham ; Toellner, Kai-Michael ; Henderson, Ian ; López-Macías, Constantino ; MacLennan, Calman A. ; Cunningham, Adam. / IgG Responses to Porins and Lipopolysaccharide within an Outer Membrane-Based Vaccine against Nontyphoidal Develop at Discordant Rates. In: mBio. 2018 ; Vol. 9, No. 2.

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@article{cbf47db991914d2e8d82aa3893c5cb0e,
title = "IgG Responses to Porins and Lipopolysaccharide within an Outer Membrane-Based Vaccine against Nontyphoidal Develop at Discordant Rates",
abstract = "Antibodies acquired after vaccination or natural infection with Gram-negative bacteria, such as invasive Salmonella enterica serovar Typhimurium, can protect against disease. Immunization with naturally shed outer membrane vesicles from Gram-negative bacteria is being studied for its potential to protect against many infections, since antigens within vesicles maintain their natural conformation and orientation. Shedding can be enhanced through genetic modification, and the resulting particles, generalized modules for membrane antigens (GMMA), not only offer potential as vaccines but also can facilitate the study of B-cell responses to bacterial antigens. Here we show that the response to immunization with GMMA from S Typhimurium (STmGMMA) provides B-cell-dependent protection and induces antibodies to two immunodominant antigens, lipopolysaccharide (LPS) and porins. Antibodies to LPS O antigen (O-Ag) markedly enhance protection in the spleen, but this effect is less marked in the liver. Strikingly, IgG responses to LPS and porins develop with distinct kinetics. In the first week after immunization, there is a dramatic T-cell-independent B1b-cell-associated induction of all IgG isotypes, except IgG1, to porins but not to LPS. In contrast, production of IgG1 to either antigen was delayed and T cell dependent. Nevertheless, after 1 month, cells in the bone marrow secreting IgG against porins or LPS were present at a similar frequency. Unexpectedly, immunization with O-Ag-deficient STmGMMA did not substantially enhance the anti-porin response. Therefore, IgG switching to all antigens does not develop synchronously within the same complex and so the rate of IgG switching to a single component does not necessarily reflect its frequency within the antigenic complex.IMPORTANCE Vaccines save millions of lives, yet for some infections there are none. This includes some types of Salmonella infections, killing hundreds of thousands of people annually. We show how a new type of vaccine, called GMMA, that is made from blebs shed from the Salmonella cell wall, works to protect against infection in mice by inducing host proteins (antibodies) specifically recognizing bacterial components (antigens). The rate of development of IgG antibody to antigens within GMMA occurred with different kinetics. However, the antibody response to GMMA persists and is likely to provide prolonged protection for those who need it. These results help show how antibody responses to bacterial antigens develop and how vaccines like GMMA can work and help prevent infection.",
keywords = "antibodies, B-cell responses, infection, outer membrane vesicles, vaccines, Salmonella",
author = "Anna Schager and Dominguez-Medina, {Carmen C.} and Francesca Necchi and Francesca Micoli and Goh, {Yun Shan} and Margaret Goodall and Adriana Flores-Langarica and Saeeda Bobat and Charlotte Cook and Melissa Arcuri and Arianna Marini and King, {Lloyd David William} and Faye Morris and Graham Anderson and Kai-Michael Toellner and Ian Henderson and Constantino L{\'o}pez-Mac{\'i}as and MacLennan, {Calman A.} and Adam Cunningham",
note = "Copyright {\textcopyright} 2018 Schager et al.",
year = "2018",
month = mar,
day = "6",
doi = "10.1128/mBio.02379-17",
language = "English",
volume = "9",
journal = "mBio",
issn = "2150-7511",
publisher = "American Society for Microbiology",
number = "2",

}

RIS

TY - JOUR

T1 - IgG Responses to Porins and Lipopolysaccharide within an Outer Membrane-Based Vaccine against Nontyphoidal Develop at Discordant Rates

AU - Schager, Anna

AU - Dominguez-Medina, Carmen C.

AU - Necchi, Francesca

AU - Micoli, Francesca

AU - Goh, Yun Shan

AU - Goodall, Margaret

AU - Flores-Langarica, Adriana

AU - Bobat, Saeeda

AU - Cook, Charlotte

AU - Arcuri, Melissa

AU - Marini, Arianna

AU - King, Lloyd David William

AU - Morris, Faye

AU - Anderson, Graham

AU - Toellner, Kai-Michael

AU - Henderson, Ian

AU - López-Macías, Constantino

AU - MacLennan, Calman A.

AU - Cunningham, Adam

N1 - Copyright © 2018 Schager et al.

PY - 2018/3/6

Y1 - 2018/3/6

N2 - Antibodies acquired after vaccination or natural infection with Gram-negative bacteria, such as invasive Salmonella enterica serovar Typhimurium, can protect against disease. Immunization with naturally shed outer membrane vesicles from Gram-negative bacteria is being studied for its potential to protect against many infections, since antigens within vesicles maintain their natural conformation and orientation. Shedding can be enhanced through genetic modification, and the resulting particles, generalized modules for membrane antigens (GMMA), not only offer potential as vaccines but also can facilitate the study of B-cell responses to bacterial antigens. Here we show that the response to immunization with GMMA from S Typhimurium (STmGMMA) provides B-cell-dependent protection and induces antibodies to two immunodominant antigens, lipopolysaccharide (LPS) and porins. Antibodies to LPS O antigen (O-Ag) markedly enhance protection in the spleen, but this effect is less marked in the liver. Strikingly, IgG responses to LPS and porins develop with distinct kinetics. In the first week after immunization, there is a dramatic T-cell-independent B1b-cell-associated induction of all IgG isotypes, except IgG1, to porins but not to LPS. In contrast, production of IgG1 to either antigen was delayed and T cell dependent. Nevertheless, after 1 month, cells in the bone marrow secreting IgG against porins or LPS were present at a similar frequency. Unexpectedly, immunization with O-Ag-deficient STmGMMA did not substantially enhance the anti-porin response. Therefore, IgG switching to all antigens does not develop synchronously within the same complex and so the rate of IgG switching to a single component does not necessarily reflect its frequency within the antigenic complex.IMPORTANCE Vaccines save millions of lives, yet for some infections there are none. This includes some types of Salmonella infections, killing hundreds of thousands of people annually. We show how a new type of vaccine, called GMMA, that is made from blebs shed from the Salmonella cell wall, works to protect against infection in mice by inducing host proteins (antibodies) specifically recognizing bacterial components (antigens). The rate of development of IgG antibody to antigens within GMMA occurred with different kinetics. However, the antibody response to GMMA persists and is likely to provide prolonged protection for those who need it. These results help show how antibody responses to bacterial antigens develop and how vaccines like GMMA can work and help prevent infection.

AB - Antibodies acquired after vaccination or natural infection with Gram-negative bacteria, such as invasive Salmonella enterica serovar Typhimurium, can protect against disease. Immunization with naturally shed outer membrane vesicles from Gram-negative bacteria is being studied for its potential to protect against many infections, since antigens within vesicles maintain their natural conformation and orientation. Shedding can be enhanced through genetic modification, and the resulting particles, generalized modules for membrane antigens (GMMA), not only offer potential as vaccines but also can facilitate the study of B-cell responses to bacterial antigens. Here we show that the response to immunization with GMMA from S Typhimurium (STmGMMA) provides B-cell-dependent protection and induces antibodies to two immunodominant antigens, lipopolysaccharide (LPS) and porins. Antibodies to LPS O antigen (O-Ag) markedly enhance protection in the spleen, but this effect is less marked in the liver. Strikingly, IgG responses to LPS and porins develop with distinct kinetics. In the first week after immunization, there is a dramatic T-cell-independent B1b-cell-associated induction of all IgG isotypes, except IgG1, to porins but not to LPS. In contrast, production of IgG1 to either antigen was delayed and T cell dependent. Nevertheless, after 1 month, cells in the bone marrow secreting IgG against porins or LPS were present at a similar frequency. Unexpectedly, immunization with O-Ag-deficient STmGMMA did not substantially enhance the anti-porin response. Therefore, IgG switching to all antigens does not develop synchronously within the same complex and so the rate of IgG switching to a single component does not necessarily reflect its frequency within the antigenic complex.IMPORTANCE Vaccines save millions of lives, yet for some infections there are none. This includes some types of Salmonella infections, killing hundreds of thousands of people annually. We show how a new type of vaccine, called GMMA, that is made from blebs shed from the Salmonella cell wall, works to protect against infection in mice by inducing host proteins (antibodies) specifically recognizing bacterial components (antigens). The rate of development of IgG antibody to antigens within GMMA occurred with different kinetics. However, the antibody response to GMMA persists and is likely to provide prolonged protection for those who need it. These results help show how antibody responses to bacterial antigens develop and how vaccines like GMMA can work and help prevent infection.

KW - antibodies

KW - B-cell responses

KW - infection

KW - outer membrane vesicles

KW - vaccines

KW - Salmonella

UR - http://www.scopus.com/inward/record.url?scp=85046468501&partnerID=8YFLogxK

U2 - 10.1128/mBio.02379-17

DO - 10.1128/mBio.02379-17

M3 - Article

C2 - 29511082

AN - SCOPUS:85046468501

VL - 9

JO - mBio

JF - mBio

SN - 2150-7511

IS - 2

M1 - e02379-17

ER -