Living With Insect-Produced Vaccines

The 2012-2013 flu season in the US has been severe increasing demand for flu vaccine. Due to problems producing enough vaccine in a short period of time, vaccine producers are turning to insect cells to solve the problem.

What is a flu vaccine?
Flu vaccines are made from a flu virus protein, typically a hemagglutinin. Injection of a vaccine containing a hemagglutinin protein stimulates the immune system to produce large numbers antibodies that recognize and attack the protein. Antibodies prevent the protein (and thus the virus) from attaching to cells or from entering the cell. This neutralizes the virus. A vaccinated individual will have antibodies that will neutralize the virus before it can replicate. Without immunization, the virus can replicate and cause influenza before the body can create the antibodies needed to attack the virus.

Why are new vaccines required every year?
The influenza virus hemagglutinin is a variable protein with a rapid mutation rate. The virus can only survive if it can escape detection. Influenza strains (new mutants) appear every year that can escape detection. Immunity to the influenza strain prevalent in the previous year does not confer immunity to the new strain. Thus, every year, the new strain must be anticipated and the new mutant form of hemagglutinin identified and reproduced.

How is hemagglutinin produced?
Influenza viruses are primarily bird viruses that replicate rapidly in bird cells. If a flu virus is injected into a chicken egg, the virus will replicate and the egg will contain large amounts of the virus and the hemagglutinin. Early vaccines used “killed” virus, but vaccines can be made from the hemagglutinin alone. Production in eggs is tedious, time consuming and virus mutations can make the vaccine lots variable. Modern molecular biology allows the genes for hemagglutinin to be rapidly cloned and inserted into cells. Cells can be grown in large vats of nutrient broth and produce copious amounts of proteins.

Why use insect cells?

Cells of Fall Armyworm used to produce proteins for Flu Vaccines
Image: ProteinSciences.com

The hemagglutinin proteins of flu viruses have sugars attached to the protein. Bacterial cells will not attach sugars to proteins, so the protein must be processed in an eukaryotic cell. Unlike bacteria, insect have eukaryotic cells that correctly process (glycosylate) the protein. Insect cell cultures have been used for production of glycoproteins for decades. The methods for their large scale growth and collection of the proteins are robust. Thus, insect cells are an excellent system for producing the large amounts of hemagglutinin needed to produce an influenza vaccine. The use of the cloned hemagglutinin is safer and less likely to have adverse side effects than virus produced in chicken eggs. In insect cells, the vaccine can be produced in greater quantities and in a shorter time than by using chicken eggs. Timeliness is critical in a flu epidemic. Thus we can expect to see increased use of insect cells in vaccine production.