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Vaccines 101

The Future of Immunization

Last updated 20 April 2022

Vaccines have been a part of the human fight against disease for more than 200 years. The worldwide vaccination campaign eradicated smallpox, and immunization has eliminated polio in all but a handful of countries. Childhood vaccination has substantially reduced the morbidity and mortality of infectious diseases in much of the developed world, and yearly influenza vaccination is a commonly accepted practice worldwide to reduce the impact of the seasonal influenza infection.

While we can attribute many public health successes to vaccination, the future presents continued challenges. Diseases remain for which researchers have been unable to find effective vaccines (such as HIV/AIDS, malaria, and leishmaniasis) or that flourish in areas of the world where infrastructures for vaccination are poor or nonexistent, and even the currently available vaccines cannot be delivered. In other cases, the cost of vaccines is too high for poorer countries to afford, even though this is often where they are most needed. And, of course, although many current vaccines are highly effective, efforts continue to develop vaccines that are more effective than those available today. Thus, researchers continue to explore new possibilities. Higher effectiveness, lower cost, and convenient delivery are some of the main goals.

 

New Development Techniques

The first vaccine—the smallpox vaccine—consisted of a live, attenuated virus. “Attenuation” means weakening a virus to the point where it can still provoke an immune response, but doesn’t cause illness in a human host.

Many of the vaccines used today, including those for measles and some influenza vaccines, use live, attenuated viruses. Others used killed forms of viruses, pieces of bacteria, or inactivated forms of toxins that the bacteria create. Killed viruses, pieces of bacteria and inactivated toxins can’t cause illness, but can still provoke an immune response that protects against future infection.

However, new techniques are also being employed to create different types of vaccines. Some of these new types include:

  • Live recombinant vaccines
  • DNA vaccines
  • mRNA vaccines

Live recombinant vaccines use attenuated viruses (or bacterial strains) as vectors: a virus or bacterium from one disease essentially acts as a delivery device for an immunogenic protein from another infectious agent. In some cases, this approach is used to enhance the immune response; in others, it is used when giving the actual agent as a vaccine would cause disease. For example, HIV cannot be attenuated enough to be given as a vaccine in humans—the risk of disease is too high.

Starting with a complete virus, researchers identify a section of the virus’s DNA that is not necessary for replication. One or more genes that code for immunogens of other pathogens are then inserted into this region. (Each gene essentially contains instructions that tell the body how to make a certain protein. In this case, researchers select genes that code for a protein specific to the target pathogen: an immunogen that will generate an immune response to that pathogen.) For example, a baculovirus (a virus that only infects insects) can be used as a vector, and the gene for a particular immunogenic surface protein of an influenza virus may be inserted. 

When the modified virus is introduced into a person’s body, the immunogen is expressed and presented, generating an immune response against the immunogen—and therefore, against the pathogen it originates from. In addition to insect viruses, human adenoviruses have been considered potential vectors for use in recombinant vaccines, particularly against diseases such as AIDS. The vaccinia virus, which is the basis for the smallpox vaccine, was the first used in live recombinant vaccine approaches.Experimental recombinant vaccinia strains have been designed to protect against influenza, rabies, and hepatitis B, among other diseases. 

DNA vaccines consist of DNA coding for a particular antigen, which is directly injected into the muscle. The DNA itself inserts into the individual’s cells, which then produce the antigen from the infectious agent. Since this antigen is foreign, it generates an immune response. This type of vaccine is relatively easy to produce, since DNA is stable and easy to manufacture, but is still experimental, because no DNA-based vaccines have been shown to elicit the substantial immune response required to prevent infection. Researchers hope DNA vaccines can generate immunity against parasitic diseases, such as malaria—currently, there is no human vaccine in use against a parasite.

mRNA vaccines aim to deliver a snippet of messenger RNA (ribonucleic acid) to a cell, so that the cell's protein-producing machinery can create a protein. That protein created from the mRNA code resembles the protein of a pathogen (virus, bacteria, fungus, or parasite) that triggers an immune response. The protein is then "presented" to immune cells to kick off the immune response consisting of killer cells and antibody-producing cells. All of this allows vaccines to include no part of the pathogen for which the vaccine is created. All researchers would need is the genetic code of the protein to be created by the recipient's cells. As of April 2020, the only licensed mRNA vaccines in the world are against SARS CoV-2, the virus causing the COVID-19 pandemic.[5, 6]

 

New Delivery Techniques

When you think of vaccination, you probably think of a doctor or nurse administering a shot. Future immunization delivery methods, however, may differ from what we use today.

Inhaled vaccines, for example, are already used in some cases: influenza vaccines have been made in a nasal spray. One of these vaccines is available every year for seasonal flu. Other possibilities include a patch application, where a patch containing a matrix of extremely tiny needles delivers a vaccine without the use of a syringe. This method of delivery could be particularly useful in remote areas, as its application would not require a trained medical person, which is generally needed for vaccines delivered as a shot by syringe.

Another issue researchers are trying to address is the so-called cold chain problem. Many vaccines require cool storage temperatures to remain viable. Unfortunately, temperature-controlled storage is often unavailable in parts of the world where vaccination is vital for disease control. One of the reasons smallpox eradication was successful was that the smallpox vaccine could be stored at relatively high temperatures and remain viable for reasonable periods. However, some contemporary vaccines cannot withstand such temperatures. The eruption of the Eyjafjallaajokull volcano in Iceland in April 2010 brought air traffic to a standstill in Northern Europe, including planes carrying 15 million doses of polio vaccine bound for West Africa. Officials feared the delay in delivering the vaccines would allow polio to spread, or that temperatures in the cargo holds of the grounded planes would render the vaccines ineffective.

Such situations highlight the need for vaccine materials that can be easily transported in various conditions and still remain viable. One possible approach to this problem was studied in early 2010 by researchers at the Jenner Institute of the University of Oxford. Starting with a small filter-like membrane, the researchers coated it with an ultrathin layer of sugar glass, with viral particles trapped inside it. In this form, the viruses the researchers used could be stored at temperatures of up to 113°F for six months, without losing their ability to provoke an immune response. By comparison, when stored in liquid storage at 113°F for just one week, one of the two viruses tested was essentially destroyed.

The researchers also demonstrated that the vaccine material could be placed in a holder designed to attach to a syringe, allowing a vaccinator to prepare the vaccine material (with a fluid medium inside the syringe) and administer the vaccine almost simultaneously.

Although this research was preliminary, it offers a promising new avenue for vaccine storage and delivery. With a stabilization method like this, widespread vaccination campaigns may be possible in areas previously difficult or impossible to reach.

The future of immunization depends on the success of medical research for vaccines that are simpler to administer, survive transport even without refrigeration, and provide a more substantial and long-lasting immune response. And in parallel, the continuing success of vaccines against so many infectious diseases has inspired scientists to use similar methods to combat diseases that remain lethal to many people, such as malaria, HIV/AIDS, and other diseases for which there are not yet effective vaccines. 

 

Sources

  1. Plotkin, S., Mortimer, E. Vaccines. New York: Harper Perennial; 1988.
  2. Fominyen, G. . Updated April 20, 2010. Accessed 01/10/2018.
  3. Carvalho, J.A., Rodgers, J., Atouguia, J., Prazeres, D.M., Monteiro, G.A. DNA vaccines: a rational design against parasitic diseases. Expert Rev Vaccines. 2010 Feb;9(2):175-91.
  4. Alcock, R., Cottingham, M., Rollier, C., et al. Long-Term Thermostabilization of Live Poxviral and Adenoviral Vaccine Vectors at Supraphysiological Temperatures in Carbohydrate Glass. Sci. Transl. Med. 2010;  2(19), 19ra12.
  5. Jain S, Venkataraman A, Wechsler ME, Peppas NA. Messenger RNA-based vaccines: Past, present, and future directions in the context of the COVID-19 pandemic. Adv Drug Deliv Rev. 2021 Oct 9;179:114000. doi: 10.1016/j.addr.2021.114000. Epub ahead of print. PMID: 34637846; PMCID: PMC8502079.

  6. Verbeke R, Lentacker I, De Smedt SC, Dewitte H. The dawn of mRNA vaccines: The COVID-19 case. J Control Release. 2021 May 10;333:511-520. doi: 10.1016/j.jconrel.2021.03.043. Epub 2021 Mar 30. PMID: 33798667; PMCID: PMC8008785.