GAVI is very interested in funding projects that provide novel delivery mechanis

Question

GAVI is very interested in funding projects that provide novel delivery mechanisms for vaccines. Dr. Bimmel has always wanted to find a way to make a vaccine for S. pneumoniae that targets all of the serotypes! This may be her opportunity! Her goal is one vaccine that would be completely protective against all strains of S. pneumoniae. She has an idea to make an edible vaccine that would contain the antigen derived from S. pneumoniae. Dr. Bimmel decides to try using yogurt as the delivery mechanism! She wants to clone a gene from S. pneumoniae that encodes an antigen and to express this gene in a microorganism that would grow in yogurt. Eating the yogurt would serve as the vaccine delivery. Consider the various molecules expressed by S. pneumoniae.

For the vaccine she must incorporate the gene for the S. pneumoniae antigen into a bacterium that will survive in the yogurt and will express the gene producing the antigen molecule. One organism found in yogurt is Streptococcus thermophilus. Dr. Bimmel begins her plan to transform S. thermophilus with a plasmid vector encoding the antigen gene.

First Dr. Bimmel must choose a plasmid cloning vector. Dr. Bimmel understands that a gene encoding resistance to antibiotics is commonly used to select for recombinant organisms (she does not want to include such a gene in her final construct for fear that it would be transferred to normal flora in the gut of the immunized children). As such, her final recombinant S. thermophilus strain will need some further genetic manipulations. However, for a phase one study, where the vaccine will be tested in the laboratory in animals, it is ok.

1) Is Dr. Bimmel right to be concerned about the presence of antibiotic resistance genes, even in the absence of selection? What are the risks (if any( of leaving the antibiotic resistance genes in the vector for the final product? What are the advantages (if any) of leaving the antibiotic resistance genes in the plasmids?

Explanation / Answer

Yes, she right to be concerned about leaving an antibiotic gene in the delivery mechanism. This is because this antibiotic resistance gene can be taken up by other bacteria which if are pathogenic will thrive even in the presence of that antibiotic that we may take as a treatment.

The advantage is off course and easy selection of the transformed bacteria. Another advantage might be to protect these bacteria which are acting as vectors in presence of antibiotics. If these bacteria containing the gene of interest were to be killed, the deliver vehicle would be killed and the experiment to develop vaccine against S. Penumoniae would fail.

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