Types of Vaccine & Manufacturing Methods

Types of vaccine

Two types of influenza vaccines are available:

• TIV (flu shot (injection) of trivalent (three strains; usually A/H1N1, A/H3N2, and B) inactivated (killed) vaccine) or
• LAIV (nasal spray (mist) of live attenuated influenza vaccine.)

TIV works by putting into the bloodstream those parts of three strains of flu virus that the body uses to create antibodies; while LAIV works by inoculating the body with those same three strains, but in a modified form that cannot cause illness.

LAIV is not recommended for individuals under age 2 or over age 50, but might be comparatively more effective among children over age 2.

Manufacturing methods

For the inactivated vaccines, the virus is grown by injecting it, along with some antibiotics, into fertilized chicken eggs. About one to two eggs are needed to make each dose of vaccine.The virus replicates within the allantois of the embryo, which is the equivalent of the placenta in mammals. The fluid in this structure is removed and the virus purified from this fluid by methods such as filtration or centrifugation. The purified viruses are then inactivated ("killed") with a small amount of a disinfectant. The inactivated virus is treated with detergent to break up the virus particles and the proteins released concentrated by centrifugation. The final preparation is suspended in sterile phosphate buffered saline ready for injection. The final product contains the viral proteins in phosphate buffered saline. It may also contain trace amounts of egg proteins and trace residues of the antibiotics, disinfectant and detergent used in the manufacturing process. In multi-dose versions of the vaccine, the preservative thimerosal is added to prevent growth of bacteria. In some versions of the vaccine used in Europe and Canada, such as Arepanrix and Fluad, an adjuvant is also added, this contains a fish oil called squalene, vitamin E and an emulsifier called polysorbate 80.

For the live vaccine, the virus is first adapted to growth at 25°C and grown at this temperature until it loses the ability to cause illness in humans, which would require the virus to grow at our normal body temperature of 37°C. This process seems to be irreversible, since once the virus has lost virulence (become "attenuated"), it cannot regain the ability to infect people. To make the vaccine, the attenuated virus is grown in chicken eggs as before. The virus-containing fluid is harvested and the virus purified by filtration; this step also removes any contaminating bacteria. The filtered preparation is then diluted into a solution that stabilizes the virus. This solution contains monosodium glutamate, potassium phosphate, gelatin, the antibiotic gentamicin, and sugar.

A new method of producing influenza virus is used to produce the Novartis vaccine Optaflu. In this vaccine the virus is grown in cell culture instead of in eggs. This method is faster than the classic egg-based system and removes the need to use antibiotics and preservatives. There are also no traces of egg proteins in the final product, so the vaccine is safe for people with egg allergies.