Faculty Collaboration Database

Multi-valent human monoclonal antibody preparation against Pseudomonas aeruginosa derived from transgenic mice containing human immunoglobulin loci is protective against fatal pseudomonas sepsis caused by multiple serotypes. Vaccine 2005 May 09;23(25):3264-71

Date

04/20/2005

Pubmed ID

15837231

DOI

10.1016/j.vaccine.2005.01.088

Scopus ID

2-s2.0-17144363627 (requires institutional sign-in at Scopus site)   30 Citations

Abstract

Pseudomonas aeruginosa is a serious human pathogen in a variety of patient groups including those with burns, hospitalized in intensive care, cystic fibrosis and neutropenia. Since there is no vaccine available, passive antibody prophylaxis against protective epitopes is an alternative strategy to prevent P. aeruginosa infection. However, immunoglobulin derived from multiple donors has variable anti-pseudomonas antibody titers, and human Mab are difficult to make from patient samples. We previously reported the use of XenoMouse mice, Ig-inactivated transgenic mice reconstituted with human immunoglobulin loci, to generate human Mab against a single serotype of P. aeruginosa lipopolysaccharide O-specific side chain (PS). We now report the creation of a panel of anti-PS human IgG2 Mab against nine additional O-specific side chain P. aeruginosa serotypes. The majority of the Mab were highly opsonic for uptake and killing of homologous P. aeruginosa by human PMN in the presence of human complement, and all the Mab protected cyclophosphamide-induced neutropenic mice from fatal P. aeruginosa sepsis with homologous serotypes. DNA sequence analysis showed that the Mab used V(H)3, V(H)4, V(H)5 and V(H)6 and Vkappa2, 3 and 4 variable region genes consistent with the heterogeneity of P. aeruginosa LPS O-side chain structure. We conclude that human Mab made in these transgenic mice against common pathogenic serotypes of P. aeruginosa are opsonic and highly protective, and that a high titer, multi-valent human Mab preparation against the majority of circulating O-side chain serotypes of P. aeruginosa could be used as prophylaxis against invasive infections in selected patient groups.

Author List

Lai Z, Kimmel R, Petersen S, Thomas S, Pier G, Bezabeh B, Luo R, Schreiber JR

MESH terms used to index this publication - Major topics in bold

Animals
Antibodies, Monoclonal
Cyclophosphamide
Enzyme-Linked Immunosorbent Assay
Humans
Immunization
Immunoglobulin G
Immunoglobulins
Immunosuppressive Agents
Lipopolysaccharides
Mice
Mice, Transgenic
Molecular Weight
Neutropenia
Pseudomonas Infections
Pseudomonas aeruginosa
Sepsis