Vaccines Laboratory

Virology: Vaccines and Other Biologics

At the Centre for Vaccine Evaluation, viruses are studied in order to improve assays for viral vaccines and other biologics.

 

Why we study viruses and vaccines

Viruses:

Viruses are small infectious particles composed of genetic material (DNA or RNA) surrounded by a protein coat. They are not capable of growth or replication outside a living organism. Viruses generally initiate infections through one of three common routes. For example, Hepatitis A virus infects the gastrointestinal system and is transmitted orally through under-cooked food. Influenza viruses initiate infection in the respiratory pathway and are transmitted through inhalation. Yellow fever viruses initiate infection in cells of the immune system and are transmitted directly through blood. Because of the health risk posed by certain types of viruses, some biological products are screened for the presence of specific viral pathogens.

Vaccines:

The immune system can recognize previously encountered pathogens. This function is the reason why many pathogens are unable to cause serious infections in a person the second time that the person encounters it.

Vaccines are biologic agents that trigger this immunological memory through a small or pseudo first infection. This immune system “preview” allows a more rapid and complete response when the real pathogen is encountered, preventing or lessening the severity of the infection.

In 1796, Edward Jenner demonstrated that infection by the cow-pox virus (vaccinia virus) prevented a subsequent infection by the smallpox virus (variola virus) after observing that milk-maids were seemingly immune to the devastating effects of smallpox. This protective demonstration has since developed into world-wide public health programs to prevent the transmission of serious human pathogens.

In Canada, we are currently using three types of viral vaccines:

  • Subunit vaccines;
  • Inactivated virus particles;
  • Live attenuated virus particles.

Subunit vaccines are composed of recombinant viral proteins as well as an immunostimulatory molecule called an adjuvant. These vaccine types have good safety profiles as all of the components are purified and characterized. However, subunit vaccines tend to be more expensive and induce a smaller immune response when compared with live attenuated vaccines.

Inactivated whole viruses can also be used as vaccines. In these vaccines, viruses are grown in vaccine-approved cell lines, purified and inactivated. The killed virus vaccines are also given with an adjuvant to boost the immune response.

Live attenuated viral vaccines are made up of infectious viruses that have been changed, so that they cannot start a systemic infection. Some types can infect single cells, but cannot replicate.

 

How We Study Viruses and Vaccines

While enzyme-linked immunosorbent assays (ELISAs) are a standard method for quantifying protein antigens in matrices such as vaccines, the assays have several limitations. ELISAs use a relatively large amount of resources per assay (antibodies, time) and are only capable of examining one analyte per reaction. A relatively simple vaccine containing two antigens would require two ELISAs per vaccine lot. If the vaccine had more than two antigenic components or was part of a multi-component vaccine, the number of ELISAs required would increase, quickly multiplying the work required for analysis. Recently, bead-based immunoassays have been developed that use a flow cytometry–based approach. This approach has been used to detect cytokines, pathogens and antibodies. The advantages of these assays are increased speed, reproducibility, and multiplexing or the capacity to simultaneously detect the multiple analytes.

 

Research Highlight 1: Rapid Batch Testing of Vaccines

Currently, we are developing several bead-based immunoassays for multi-component vaccines. We will compare the accuracy, sensitivity, speed and cost of these methods with the single radial immuno-diffusion (SRID) assay and universal ELISAs currently used to evaluate vaccine lots.

We are working to:

  • Develop an assay to quantify components of anti-viral vaccines.

 

Research Highlight 2: Development of New Polio Virus Vaccine Potency Test.

In Canada, licensed poliovirus vaccines consist of inactivated poliovirus derived from wild-type strains.Once transmission of wild-type poliovirus is stopped world-wide (Polio Eradication Initiative, WHO), all vaccine production will shift to using only inactivated poliovirus derived from attenuated strains. The potency of these new vaccines cannot be quantified using the currently approved testing regime.

We are working to:

  • Develop a new test for the quantification of inactivated poliovirus vaccines derived from attenuated poliovirus strains.

 

For information about the lead scientist of this laboratory, please visit their  Directory of Scientists and Professionals profile.

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