Cargando…
Augmenting Vaccine Immunogenicity through the Use of Natural Human Anti-rhamnose Antibodies
[Image: see text] Utilizing natural antibodies to augment vaccine immunogenicity is a promising approach toward cancer immunotherapy. Anti-rhamnose (anti-Rha) antibodies are some of the most common natural anti-carbohydrate antibodies present in human serum. Therefore, rhamnose can be utilized as a...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical
Society
2018
|
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6103300/ https://www.ncbi.nlm.nih.gov/pubmed/29916701 http://dx.doi.org/10.1021/acschembio.8b00312 |
_version_ | 1783349326707163136 |
---|---|
author | Hossain, Md Kamal Vartak, Abhishek Karmakar, Partha Sucheck, Steven J. Wall, Katherine A. |
author_facet | Hossain, Md Kamal Vartak, Abhishek Karmakar, Partha Sucheck, Steven J. Wall, Katherine A. |
author_sort | Hossain, Md Kamal |
collection | PubMed |
description | [Image: see text] Utilizing natural antibodies to augment vaccine immunogenicity is a promising approach toward cancer immunotherapy. Anti-rhamnose (anti-Rha) antibodies are some of the most common natural anti-carbohydrate antibodies present in human serum. Therefore, rhamnose can be utilized as a targeting moiety for a rhamnose-containing vaccine to prepare an effective vaccine formulation. It was shown previously that anti-Rha antibody generated in mice binds effectively with Rha-conjugated vaccine and is picked up by antigen presenting cells (APCs) through stimulatory Fc receptors. This leads to the effective uptake and processing of antigen and eventually presentation by major histocompatibility complex (MHC) molecules. In this article, we show that natural human anti-Rha antibodies can also be used in a similar mechanism and immunogenicity can be enhanced by targeting Rha-conjugated antigens. In doing so, we have purified human anti-Rha antibodies from human serum using a rhamnose affinity column. In vitro, human anti-Rha antibodies are shown to enhance the uptake of a model antigen, Rha-ovalbumin (Rha-Ova), by APCs. In vivo, they improved the priming of CD4+ T cells to Rha-Ova in comparison to non-anti-Rha human antibodies. Additionally, increased priming of both CD4+ and CD8+ T cells toward the cancer antigen MUC1-Tn was observed in mice that received human anti-Rha antibodies prior to vaccination with a rhamnose-modified MUC1-Tn cancer vaccine. The vaccine conjugate contained Pam(3)CysSK(4), a Toll-like receptor (TLR) agonist linked via copper-free cycloaddition chemistry to a 20-amino-acid glycopeptide derived from the tumor marker MUC-1 containing the tumor-associated carbohydrate antigen α-N-acetyl galactosamine (GalNAc). The primed CD8+ T cells released IFN-γ and killed tumor cells. Therefore, we have confirmed that human anti-Rha antibodies can be effectively utilized as a targeting moiety for making an effective vaccine. |
format | Online Article Text |
id | pubmed-6103300 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | American Chemical
Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-61033002019-06-19 Augmenting Vaccine Immunogenicity through the Use of Natural Human Anti-rhamnose Antibodies Hossain, Md Kamal Vartak, Abhishek Karmakar, Partha Sucheck, Steven J. Wall, Katherine A. ACS Chem Biol [Image: see text] Utilizing natural antibodies to augment vaccine immunogenicity is a promising approach toward cancer immunotherapy. Anti-rhamnose (anti-Rha) antibodies are some of the most common natural anti-carbohydrate antibodies present in human serum. Therefore, rhamnose can be utilized as a targeting moiety for a rhamnose-containing vaccine to prepare an effective vaccine formulation. It was shown previously that anti-Rha antibody generated in mice binds effectively with Rha-conjugated vaccine and is picked up by antigen presenting cells (APCs) through stimulatory Fc receptors. This leads to the effective uptake and processing of antigen and eventually presentation by major histocompatibility complex (MHC) molecules. In this article, we show that natural human anti-Rha antibodies can also be used in a similar mechanism and immunogenicity can be enhanced by targeting Rha-conjugated antigens. In doing so, we have purified human anti-Rha antibodies from human serum using a rhamnose affinity column. In vitro, human anti-Rha antibodies are shown to enhance the uptake of a model antigen, Rha-ovalbumin (Rha-Ova), by APCs. In vivo, they improved the priming of CD4+ T cells to Rha-Ova in comparison to non-anti-Rha human antibodies. Additionally, increased priming of both CD4+ and CD8+ T cells toward the cancer antigen MUC1-Tn was observed in mice that received human anti-Rha antibodies prior to vaccination with a rhamnose-modified MUC1-Tn cancer vaccine. The vaccine conjugate contained Pam(3)CysSK(4), a Toll-like receptor (TLR) agonist linked via copper-free cycloaddition chemistry to a 20-amino-acid glycopeptide derived from the tumor marker MUC-1 containing the tumor-associated carbohydrate antigen α-N-acetyl galactosamine (GalNAc). The primed CD8+ T cells released IFN-γ and killed tumor cells. Therefore, we have confirmed that human anti-Rha antibodies can be effectively utilized as a targeting moiety for making an effective vaccine. American Chemical Society 2018-06-19 2018-08-17 /pmc/articles/PMC6103300/ /pubmed/29916701 http://dx.doi.org/10.1021/acschembio.8b00312 Text en Copyright © 2018 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes. |
spellingShingle | Hossain, Md Kamal Vartak, Abhishek Karmakar, Partha Sucheck, Steven J. Wall, Katherine A. Augmenting Vaccine Immunogenicity through the Use of Natural Human Anti-rhamnose Antibodies |
title | Augmenting Vaccine Immunogenicity through the Use
of Natural Human Anti-rhamnose Antibodies |
title_full | Augmenting Vaccine Immunogenicity through the Use
of Natural Human Anti-rhamnose Antibodies |
title_fullStr | Augmenting Vaccine Immunogenicity through the Use
of Natural Human Anti-rhamnose Antibodies |
title_full_unstemmed | Augmenting Vaccine Immunogenicity through the Use
of Natural Human Anti-rhamnose Antibodies |
title_short | Augmenting Vaccine Immunogenicity through the Use
of Natural Human Anti-rhamnose Antibodies |
title_sort | augmenting vaccine immunogenicity through the use
of natural human anti-rhamnose antibodies |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6103300/ https://www.ncbi.nlm.nih.gov/pubmed/29916701 http://dx.doi.org/10.1021/acschembio.8b00312 |
work_keys_str_mv | AT hossainmdkamal augmentingvaccineimmunogenicitythroughtheuseofnaturalhumanantirhamnoseantibodies AT vartakabhishek augmentingvaccineimmunogenicitythroughtheuseofnaturalhumanantirhamnoseantibodies AT karmakarpartha augmentingvaccineimmunogenicitythroughtheuseofnaturalhumanantirhamnoseantibodies AT sucheckstevenj augmentingvaccineimmunogenicitythroughtheuseofnaturalhumanantirhamnoseantibodies AT wallkatherinea augmentingvaccineimmunogenicitythroughtheuseofnaturalhumanantirhamnoseantibodies |