December 20th, 2016

VACCINES! VACCINES EVERYWHERE!

…well, we wish it were that easy.

Middle East Respiratory Syndrome is continuing to be a nuisance in the Eastern world, specifically the Middle East. Twenty-six countries have confirmed MERS-CoV cases totaling 1,621 with 584 deaths. A respiratory virus that can cause multiple organ failure and death, the World Health Organization, Centers for Disease Control and Prevention and country specific health organizations have been working to develop a vaccine to stop the spread of MERS-CoV.

Vaccine development is tricky; there are five major stages to vaccine development: Pre-Clinical Research, Phase I Trials, Phase II Trials, Phase III Trials, and Mass Production.

Pre-clinical Trials include genomic sequencing of the virus, determining antigens, animal testing and vaccine concept plans.

Phase I Trials are tested on a small population of individuals to determine if the vaccine is safe for use on humans and to see if there are any major adverse immune responses.

Phase II Trials consist of a larger population of individuals, typically several hundred, to determine strength of protection against artificial disease and to determine side effects.

Phase III Trials consist of several thousand individuals to determine vaccine efficacy against the natural disease.

Once the vaccine has passed all level of clinical trials, it must go through licensing and ethical review by health organizations before being approved for distribution.

How do vaccines work?

Vaccines work by mimicking an infection by causing the mobilization of the immune system to produce antibodies and T-lymphocytes (Killer T-cells). The immune system works in a variety of ways, but vaccines utilize what is called the adaptive immune system. The adaptive immune system controls antibodies and killer T-cells. Once the body encounters a disease, the immune system can produce virus specific antibodies and T-cells. The immune system can “learn” about a specific disease so that in the future, it can mount  faster, stronger defense. This is what vaccines do, they provide a weakened infection so that the immune system can “remember” that disease later.

There are two major kinds of vaccines: Live attenuated and inactivated vaccines.

Live attenuated viruses use pieces of a weakened version of the virus in order to “teach” the immune system to recognize and respond to the virus. Live attenuated viruses are the best kinds of viruses for the normal healthy population as the immune system uses a natural virus to create the defense cells. However, people with weakened immune systems (Chemo patients, individuals with AIDS, or those with autoimmune disorders) cannot receive these vaccines. Diseases that utilize live attenuated vaccines are measles, mumps and rubella (MMR) and chickenpox vaccine.

Inactivated vaccines on the other hand, use a “killed” version of the virus to teach the immune system about the virus. These normally require multiple doses boosters for the immune system to build up antibodies. Examples of inactivated vaccines are the polio vaccines and also the yearly flu vaccine (though live attenuated of the Flu vaccine is offered).

A recent study published in the American Society for Microbiology’s Journal of Virology has linked a MERS-CoV receptor protein to a vaccina virus that has been utilized in other vaccines. In order for a vaccine to be effective, it needs to be able to cause an immune response strong enough to fight off infection from the targeted disease. The candidate vaccine made by Volz et. al has completed the pre-clinical testing phase, proving effective in animal testing by inducing Killer T cells and antibody response to MERS-CoV cells. Using a recombinant Modified Vaccinia virus Ankara (MVA) which was utilized in the smallpox vaccine, researchers were able to incorporate a MERS-CoV spike glycoprotein and transduced a human dipeptidyl peptidase 4 receptor. This combination allowed immune response with both subcutaneous and intramuscular administration. While this is just the first step in vaccine development, this vaccine is a promising candidate to move on to the next trial phase.

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A. Volz, A. Kupke, F. Song, S. Jany, R. Fux, H. Shams-Eldin, J. Schmidt, C. Becker, M. Eickmann, S. Becker, G. Sutter, Protective efficacy of recombinant modified vaccinia virus Ankara delivering Middle East respiratory syndrome coronavirus spike glycoprotein. J. Virol. 89, 8651–8656 (2015). Medline doi:10.1128/JVI.00614-15

Centers for Disease Control and Prevention (CDC). 2013. Understanding how vaccines work. website: http://www.cdc.gov/vaccines/hcp/patient-ed/conversations/downloads/vacsafe-understand-color-office.pdf

University of San Francisco. Immunology Module: The innate and adaptive immune systems. website: http://missinglink.ucsf.edu/lm/immunology_module/prologue/objectives/obj02.html

December 1st