Coronavirus Structure, Vaccine
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Our blood, lymph, and organs are host to the white cells of the immune system, which are continually checking for the presence of foreign elements such as viruses, bacteria, fungi, parasites, tumor cells, and toxins. These white cells are made in the bone marrow.
One type of white cell is called a B-cell. B-cells are specific to a particular pathogen and secrete antibodies that detect that pathogen. Antibodies are proteins that bind to a foreign antigen, inactivate it, and/or target it for destruction by other white cells. When a person is infected by a foreign substance, B-cells will begin making and excreting antibodies into the bloodstream that recognize the outer surface of the pathogen. For viruses, it is often the spike proteins that are recognized. Some antibodies that bind to the viral spike proteins can prevent the viral particles from infecting the cells. Other white cells (macrophages) can engulf these compromised particles, removing them from circulation. B-cells can also keep a “memory” of the antibody that recognized a past pathogen and, in the case of another exposure, mount a response that is quicker and more efficient.
A second class of white cells are known as “killer” cells. Some of these white cells can recognize a cell that is infected by the virus and kill those cells. The phlegm that you cough up in a respiratory infection is full of debris from infected cells lysed by killer white cells.
One of the best ways to protect against infection is to stimulate the immune system with a vaccine. For example, the polio vaccine consists of inactivated viral particles. These are unable to initiate an infection but are recognized by the white cells of the immune system. Over a period of weeks, the white cells that recognize the virus reproduce in the body. These white cells synthesize and secrete antibodies that can bind to the virus in the vaccine. If the individual is then exposed to infectious poliovirus, the circulating antibodies are already present and are able to inactivate the infecting particles. This immunity may last for decades, though that differs depending on the antigen.
Developing a vaccine requires growing large amounts of virus, often in animals, or in tissue culture at large scale. The viruses are inactivated by radiation, heat, or chemicals, or are derived from genetically weakened strains. Another alternative is to purify not the complete virus, but isolated viral proteins like spike. This is safer and easier to scale up, but the immune system response to the isolated protein is often not as robust as it is to the organized lattice of the intact virus particle. A more recent strategy involves injecting individuals with RNA or DNA encoding for viral proteins. These nucleic acids can be administered alone or through man-made vectors that help deliver material into the body. In any strategy, however, enough material is needed to inject reasonable doses into millions of people.
But before doing this one has to know that the vaccine works to stimulate a protective immune response. This requires recruiting human volunteers to be vaccinated and then be challenged with the infectious virus. All of this takes time and skilled personnel and money. However, with sufficient investment, success is highly likely in most cases. Note that vaccination is typically preventive – most vaccines do not provide relief for someone already infected.
Addressing the health hazards of coronavirus infections would benefit greatly by antiviral drugs that act to block the attachment and internalization process or the replication of the virus within infected cells. Antivirals that interfere with the viral lifecycle without significantly impacting normal cellular function are critical to combating viral infections. Such therapies are in use for other RNA viruses, like influenza, and are administered generally as small molecules, taken in pill form. These antivirals act by binding to and interfering with viral proteins needed to replicate the viral RNA or facilitate binding and entry of the virus into the cell. Another class of antiviral drugs, which are effective with HIV, act by interfering with the synthesis and assembly of the coat proteins into the viral capsid. The U.S. pharmaceutical industry already has the capacity to produce millions of doses of small molecules, so the rate limiting step in this case is more likely to be at the laboratory research and development stage.
The system already lacked sufficient funds to continue with vaccine development for the SARS-CoV virus after that threat subsided. We need a scientific and biomedical research infrastructure that can respond to the next threats, and of course a healthcare system and healthcare financing that can ensure high quality treatment for all.
Jonathan King and Eric Sundberg have directed biomedical research projects on viruses and viral proteins supported by the National Institutes of Health and National Science Foundation. They are both members of the Public Affairs Committee of the Biophysical Society. Melissa Kosinski-Collins has led HHMI and AAU-funded research programs in Biology Education.
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