Intramuscular Immunization Induces Antigen-specific Antibodies in Urine.

Abstract

Towards the development of vaccines against urinary tract infections (UTI), we determined the ability of intramuscular (i.m.) immunization to result in antigen-specific antibodies in urine. As a model antigen/vaccine, levels of total and vaccine-specific antibodies were determined in urine as a spin-out study of a phase 1 trial. Non-muscle-invasive bladder cancer (NMIBC) patients at different risks of progression, undergoing intravesical bacillus Calmette-Guérin (BCG) immunotherapy or not, received an adjuvanted recombinant protein vaccine that resulted in high titers of vaccine-specific serum immunoglobulin G (IgG) in all patients, regardless of the risk group. Vaccine-specific IgG and immunoglobulin A (IgA) were detected in urine of half of the patients at low risk of progression NMIBC and in all the intermediary/high- (int/high) risk patients. Vaccine-specific IgG titers were correlated to total urinary IgG levels, the latter being higher in the int/high-risk patients. In contrast, vaccine-specific IgA did not correlate to urinary IgA levels. Furthermore, vaccine-specific antibodies were transiently increased by intravesical BCG instillations. Altogether, our data show that a standard i.m. immunization can effectively induce antigen-specific antibodies in urine, which, upon selection of optimal vaccine targets, may provide protection against UTI. Vaccine-specific IgG titers were dependent on conditions affecting total urinary IgG levels, while production of vaccine-specific IgA in situ might independently contribute to protection against infections in the bladder. PATIENT SUMMARY: Towards the development of vaccines able to protect against urinary tract infections, we examined the potential of the intramuscular vaccination using a model antigen. We found two types of specific antibodies in the urine, which together may locally contribute to protection against infections, thus supporting the use of such a standard immunization route.

• Authors: Laurent Derré, Ilaria Lucca, Valérie Cesson, Massimo Valerio, Yannick Cerantola, Rodolfo Burruni, Urs Fritschi, Dalila Gharbi, Martine Bobst, Anne-Sophie Legris, Florence Dartiguenave, Patrice Jichlinski, Denise Nardelli-Haefliger
• Journal: European urology focus (Eur Urol Focus) Vol. 6 Issue 2 Pg. 280-283 (03 15 2020) ISSN: 2405-4569 [Electronic] Netherlands
• PMID: 30219710 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Chemical References

• Adjuvants, Immunologic
• Antigens, Neoplasm
• BCG Vaccine
• Immunoglobulin A
• Immunoglobulin G
• MAGEA3 protein, human
• Neoplasm Proteins
• Vaccines, Synthetic

Topics

• Adjuvants, Immunologic (therapeutic use)
• Antigens, Neoplasm (administration & dosage, immunology)
• BCG Vaccine (therapeutic use)
• Humans
• Immunization (methods)
• Immunoglobulin A (urine)
• Immunoglobulin G (urine)
• Injections, Intramuscular
• Neoplasm Proteins (administration & dosage, immunology)
• Urinary Bladder Neoplasms (drug therapy)
• Urinary Tract Infections (prevention & control)
• Vaccines, Synthetic (administration & dosage, immunology)