ABSTRACT
Apart from the use of oral rehydration solution, there are currently no treatment modalities for rotavirus induced diarrhoea, which is particularly relevant to developing countries. Fragments derived from llama heavy chain antibodies were previously shown to be highly stable, efficiently produced in yeast and exhibiting high epitope specific affinity. We now aim to demonstrate that these antibody fragments are capable of reducing morbidity of rotavirus induced diarrhoea. Here we show the isolation of rotavirus specific antibody fragments and their capability of reducing the morbidity of rotavirus induced diarrhoea in vivo in mice. They could provide a treatment modality for the moderation of human rotavirus infections having a significant impact on the course of an often fatal childhood disease.
Subject(s)
Camelids, New World/immunology , Rotavirus Infections/prevention & control , Rotavirus/immunology , Animals , Antibodies, Viral/administration & dosage , Antibodies, Viral/genetics , Antibodies, Viral/isolation & purification , Base Sequence , DNA, Viral/genetics , Female , Humans , Immunoglobulin Fragments/administration & dosage , Immunoglobulin Fragments/genetics , Immunoglobulin Fragments/isolation & purification , In Vitro Techniques , Mice , Mice, Inbred BALB C , Neutralization Tests , Pregnancy , Rotavirus/genetics , Rotavirus/pathogenicity , Rotavirus Infections/immunology , Rotavirus Infections/therapy , Rotavirus Vaccines/administration & dosage , Rotavirus Vaccines/genetics , Rotavirus Vaccines/isolation & purification , Saccharomyces cerevisiae/geneticsABSTRACT
Bacteriophage infection is still a persistent problem in large dairy processes despite extensive studies over the last decades. Consequently, new methods are constantly sought to prevent phage infection. In this paper, we show that phage neutralizing heavy-chain antibody fragments, obtained from Camelidae and produced at a large scale in the generally regarded as safe microorganism Saccharomyces cerevisiae, can effectively be used to impede phage induced lysis during a cheese process. The growth inhibition of the cheese starter culture by 10(5) pfu/ml cheese-milk of the small isometric-headed 936-type phage p2 was prevented by the addition of only 0.1 microg/ml (7 nM) of the neutralizing antibody fragment. The use of such antibody fragments in cheese manufacturing are a realistic and interesting option because of the small amount of antibody fragments that are needed. Moreover the antibodies are produced in a food grade microorganism and can easily be isolated from the fermentation liquid in a pure and DNA free form.
