A Chlamydia trachomatis VD1-MOMP vaccine elicits cross-neutralizing and protective antibodies against C/C-related complex serovars

Abstract Ocular and urogenital infections with Chlamydia trachomatis (C.t.) are caused by a range of different serovars. The first C.t. vaccine in clinical development (CTH522/CAF®01) induced neutralizing antibodies directed to the variable domain 4 (VD4) region of major outer membrane protein (MOMP...

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Main Authors: Anja Weinreich Olsen, Ida Rosenkrands, Martin J. Holland, Peter Andersen, Frank Follmann
Format: Article
Language:English
Published: Nature Publishing Group 2021-04-01
Series:npj Vaccines
Online Access:https://doi.org/10.1038/s41541-021-00312-9
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spelling doaj-6344e9e5dba04b32bbb648fc6b8964762021-04-25T11:32:14ZengNature Publishing Groupnpj Vaccines2059-01052021-04-016111110.1038/s41541-021-00312-9A Chlamydia trachomatis VD1-MOMP vaccine elicits cross-neutralizing and protective antibodies against C/C-related complex serovarsAnja Weinreich Olsen0Ida Rosenkrands1Martin J. Holland2Peter Andersen3Frank Follmann4Center for Vaccine Research, Department of Infectious Disease Immunology, Statens Serum InstitutCenter for Vaccine Research, Department of Infectious Disease Immunology, Statens Serum InstitutClinical Research Department, London School of Hygiene & Tropical MedicineCenter for Vaccine Research, Department of Infectious Disease Immunology, Statens Serum InstitutCenter for Vaccine Research, Department of Infectious Disease Immunology, Statens Serum InstitutAbstract Ocular and urogenital infections with Chlamydia trachomatis (C.t.) are caused by a range of different serovars. The first C.t. vaccine in clinical development (CTH522/CAF®01) induced neutralizing antibodies directed to the variable domain 4 (VD4) region of major outer membrane protein (MOMP), covering predominantly B and intermediate groups of serovars. The VD1 region of MOMP contains neutralizing B-cell epitopes targeting serovars of the C and C-related complex. Using an immuno-repeat strategy, we extended the VD1 region of SvA and SvJ to include surrounding conserved segments, extVD1A and extVD1J, and repeated this region four times. The extVD1A*4 was most immunogenic with broad cross-surface and neutralizing reactivity against representative members of the C and C-related complex serovars. Importantly, in vitro results for extVD1A*4 translated into in vivo biological effects, demonstrated by in vivo neutralization of SvA and protection/cross-protection against intravaginal challenge with both SvA and the heterologous SvIa strain.https://doi.org/10.1038/s41541-021-00312-9
collection DOAJ
language English
format Article
sources DOAJ
author Anja Weinreich Olsen
Ida Rosenkrands
Martin J. Holland
Peter Andersen
Frank Follmann
spellingShingle Anja Weinreich Olsen
Ida Rosenkrands
Martin J. Holland
Peter Andersen
Frank Follmann
A Chlamydia trachomatis VD1-MOMP vaccine elicits cross-neutralizing and protective antibodies against C/C-related complex serovars
npj Vaccines
author_facet Anja Weinreich Olsen
Ida Rosenkrands
Martin J. Holland
Peter Andersen
Frank Follmann
author_sort Anja Weinreich Olsen
title A Chlamydia trachomatis VD1-MOMP vaccine elicits cross-neutralizing and protective antibodies against C/C-related complex serovars
title_short A Chlamydia trachomatis VD1-MOMP vaccine elicits cross-neutralizing and protective antibodies against C/C-related complex serovars
title_full A Chlamydia trachomatis VD1-MOMP vaccine elicits cross-neutralizing and protective antibodies against C/C-related complex serovars
title_fullStr A Chlamydia trachomatis VD1-MOMP vaccine elicits cross-neutralizing and protective antibodies against C/C-related complex serovars
title_full_unstemmed A Chlamydia trachomatis VD1-MOMP vaccine elicits cross-neutralizing and protective antibodies against C/C-related complex serovars
title_sort chlamydia trachomatis vd1-momp vaccine elicits cross-neutralizing and protective antibodies against c/c-related complex serovars
publisher Nature Publishing Group
series npj Vaccines
issn 2059-0105
publishDate 2021-04-01
description Abstract Ocular and urogenital infections with Chlamydia trachomatis (C.t.) are caused by a range of different serovars. The first C.t. vaccine in clinical development (CTH522/CAF®01) induced neutralizing antibodies directed to the variable domain 4 (VD4) region of major outer membrane protein (MOMP), covering predominantly B and intermediate groups of serovars. The VD1 region of MOMP contains neutralizing B-cell epitopes targeting serovars of the C and C-related complex. Using an immuno-repeat strategy, we extended the VD1 region of SvA and SvJ to include surrounding conserved segments, extVD1A and extVD1J, and repeated this region four times. The extVD1A*4 was most immunogenic with broad cross-surface and neutralizing reactivity against representative members of the C and C-related complex serovars. Importantly, in vitro results for extVD1A*4 translated into in vivo biological effects, demonstrated by in vivo neutralization of SvA and protection/cross-protection against intravaginal challenge with both SvA and the heterologous SvIa strain.
url https://doi.org/10.1038/s41541-021-00312-9
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