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Removal of Anti-α-Galactosyl Antibodies Elicits Protective Immunity Against Gram-Negative Bacterial Infections

64 Pages Posted: 10 Apr 2018 Sneak Peek Status: Review Complete

See all articles by Daniel Bello-Gil

Daniel Bello-Gil

Bellvitge Biomedical Research Institute (IDIBELL) - Infectious Pathology and Transplantation Division

Magdiel Perez-Cruz

Bellvitge Biomedical Research Institute (IDIBELL) - Infectious Pathology and Transplantation Division

Cristina Costa

Bellvitge Biomedical Research Institute (IDIBELL) - Infectious Pathology and Transplantation Division

Mariana Camoez

Bellvitge Biomedical Research Institute (IDIBELL) - Infectious Pathology and Transplantation Division

Angeles Dominguez

Bellvitge Biomedical Research Institute (IDIBELL) - Infectious Pathology and Transplantation Division

Sara Olivera-Ardid

Bellvitge Biomedical Research Institute (IDIBELL) - Infectious Pathology and Transplantation Division

Aitor Rodriguez-Martinez

Bellvitge Biomedical Research Institute (IDIBELL) - Infectious Pathology and Transplantation Division

Nailya Khasbiullina

Russian Academy of Sciences (RAS) - Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry

Nadezhda Shilova

Russian Presidential Academy of National Economy and Public Administration (RANEPA) - Department of Economics; National Research University Higher School of Economics

Nicolai V. Bovin

Russian Academy of Sciences (RAS) - Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry

Rafael Mañez

Bellvitge Biomedical Research Institute (IDIBELL) - Infectious Pathology and Transplantation Division

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Abstract

Antibody-dependent enhancement (ADE) of infection occurs when nonneutralizing antibodies facilitate the infectivity of pathogens. In humans, antibodies involved in ADE of infections may include those naturally produced against α-galactosyl (αGal) epitopes. Here, we investigate whether the removal of circulating anti-αGal antibodies using a soluble αGal glycopolymer confers protection against Gram-negative bacterial infections. We demonstrate that the intra-corporeal removal of anti-αGal antibodies in an α1,3-galactosyltransferase knockout mouse model is associated with protection against mortality from Gram-negative sepsis after cecal ligation and puncture. Additionally, inhibition of anti-αGal antibodies in vitro from human serum increases the bactericidal effect against E. coli O86:B7 and multi-drug resistant Pseudomonas aeruginosa and Klebsiella pneumoniae. Our results show that protective immunity against Gram-negative bacterial pathogens can be elicited and infectious diseases can be prevented by removing anti-αGal antibodies. The intracorporeal removal of non-neutralizing anti-carbohydrate antibodies with glycopolymers may represent a new approach to providing protection against infectious diseases.

Suggested Citation

Bello-Gil, Daniel and Perez-Cruz, Magdiel and Costa, Cristina and Camoez, Mariana and Dominguez, Angeles and Olivera-Ardid, Sara and Rodriguez-Martinez, Aitor and Khasbiullina, Nailya and Shilova, Nadezhda and Bovin, Nicolai V. and Mañez, Rafael, Removal of Anti-α-Galactosyl Antibodies Elicits Protective Immunity Against Gram-Negative Bacterial Infections (2018). Available at SSRN: https://ssrn.com/abstract=3155670 or http://dx.doi.org/10.2139/ssrn.3155670
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Daniel Bello-Gil

Bellvitge Biomedical Research Institute (IDIBELL) - Infectious Pathology and Transplantation Division

08908 Hospitalet de LLobregat
Spain

Magdiel Perez-Cruz

Bellvitge Biomedical Research Institute (IDIBELL) - Infectious Pathology and Transplantation Division

08908 Hospitalet de LLobregat
Spain

Cristina Costa

Bellvitge Biomedical Research Institute (IDIBELL) - Infectious Pathology and Transplantation Division

08908 Hospitalet de LLobregat
Spain

Mariana Camoez

Bellvitge Biomedical Research Institute (IDIBELL) - Infectious Pathology and Transplantation Division

08908 Hospitalet de LLobregat
Spain

Angeles Dominguez

Bellvitge Biomedical Research Institute (IDIBELL) - Infectious Pathology and Transplantation Division

08908 Hospitalet de LLobregat
Spain

Sara Olivera-Ardid

Bellvitge Biomedical Research Institute (IDIBELL) - Infectious Pathology and Transplantation Division

08908 Hospitalet de LLobregat
Spain

Aitor Rodriguez-Martinez

Bellvitge Biomedical Research Institute (IDIBELL) - Infectious Pathology and Transplantation Division

08908 Hospitalet de LLobregat
Spain

Nailya Khasbiullina

Russian Academy of Sciences (RAS) - Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry

Moscow, 117997
Russia

Nadezhda Shilova

Russian Presidential Academy of National Economy and Public Administration (RANEPA) - Department of Economics ( email )

Russia

National Research University Higher School of Economics ( email )

Myasnitskaya street, 20
Moscow, Moscow 119017
Russia

Nicolai V. Bovin

Russian Academy of Sciences (RAS) - Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry

Moscow, 117997
Russia

Rafael Mañez (Contact Author)

Bellvitge Biomedical Research Institute (IDIBELL) - Infectious Pathology and Transplantation Division ( email )

08908 Hospitalet de LLobregat
Spain

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