Wednesday, June 11, 2025

 I have text (bottom, using tabs to look through the different types) and

 I have a pre-recorded lecture (17 min but you can speed me up). 

Please choose whichever method works better for your learning.

There are many ways to make a vaccine

We use many strategies to induce a "primary response" of the immune system in order to train the immune system to recognize antigens from a pathogen. Creating cellular & humoral memory is what underlies "immunity" to a pathogen.

What does it mean to acquire immunity?

A person who is immune is someone who is resistant to particular pathogen or toxin due to:

  • producing specific antibodies that recognize that particular pathogen or toxin.

The key part of designing a vaccine is to expose the body to antigen that won't cause disease, but will provoke an immune response that can block or kill the pathogen if a person becomes infected with the real pathogen later. After a vaccine shot, some people will feel soreness or heat around the injection site. Others might even develop a slight fever and headache in the next day or so. These are all very normal reactions that indicate the vaccine is stimulating an immune response! This is not to be confused with getting sick or developing disease. Remember that it's the immune response that generates inflammation and fever symptoms and signs in people.


The material I show here illustrates the idea using a virus but please keep in mind that the same guidelines apply to bacteria and eukaryotic pathogens as well.


Review:  The Immune Response to Viral Pathogens

The figure below does a pretty great job of summarizing the basic steps that the immune system takes to generate an immune response and immunological memory to an invading viral pathogen.  The rest of this mini-lecture will focus on how the virus enters or is processed to be presented on the antigen presenting cell (APC).  After that, activation of the helper T cell (CD4), cytotoxic T cell (CD8) and B cells happen as we've discussed in lecture (or as summarized, in MUCH less detail on this figure).

Viral Vector Vaccines

This type of vaccine uses a safe virus (that doesn't cause disease) to deliver DNA or RNA instructions on how to build particular proteins of the pathogen of interest.  These safe viruses are called "vectors".  The DNA or RNA is inserted into a vector, and the vector delivers the DNA to a cell in your body where your enzymes (RNA polymerase and Ribosome) build the viral proteins to launch the immune response. 

Some of these vectors can replicate, amplifying the response and some cannot (the J&J vaccine cannot).  Notice that the viral vector vaccine doesn't contain "live" components of the pathogen so there is no risk of introducing the disease.  These viral vectors could potentially be used to introduce genetic information from any type of pathogen:  viral, bacterial, protozoal, fungal, etc. Although this approach is relatively new in vaccines, it has been used in gene therapy for many years.  

Some existing vaccines are made this way, including:

  • Johnson and Johnson COVID-19 Vaccine (authorized for emergency use in the US and other countries)
  • AstraZeneca COVID-19 Vaccine (not approved for use in the US)
  • Ebola Vaccine (new, but made a huge difference in the latest Ebola outbreak)

Take a look at the figure below to see how the immune response is generated from each of these types of vaccines.

Nucleic Acid Vaccines

Remember the viral vector vaccines?  They used a safe viral vector to introduce nucleic acids (DNA or RNA) encoding specific viral genes into your cells.  Then YOUR cells have to make the viral proteins to initiate the immune response.  Nucleic acid vaccines are just alternate ways to introduce the nucleic acids for specific viral genes into your cells.  For the mRNA vaccines, for example, a tiny mRNA with the genetic information only for a single protein are wrapped in a oily bubble of lipids that can easily fuse with your cell membranes. Once the genetic information makes it into your cells, your enzymes (RNA polymerase and Ribosomes) are used to produce the viral proteins to launch the immune response. 

As with viral vector vaccines, the vaccine doesn't contain "live" components of the pathogen so there is no risk of introducing the disease.  Also, as with viral vector vaccines, this technology could be used to introduce genetic information from any type of pathogen.  

Although this technology may be new to the routine immunization schedule, research has been progressing on mRNA vaccines for many microbes, including influenza, HIV and other coronaviruses (SARS-CoV1) since the early 1990s.  The field was primed to launch, and when the COVID-19 pandemic (and the flood of vaccine development money) hit,  the technology was primed to take off.  In contrast to more traditional vaccines (like the whole virus vaccines of Strategy #1), mRNA is super easy and fast to make, so vaccine developers are quickly ramping up production of these vaccines.  

Existing vaccines are made this way, including:

  • Pfizer COVID-19 vaccine (approved for use in the US)
  • Moderna COVID-19 vaccine (approved for emergency use in the US)

Now that the technology is up and running, there are many vaccines being developed using mRNA technology including

  • influenza
  • HIV
  • malaria
  • many, many others

Take a look at the figure below to see how the immune response is generated from each of these types of vaccines.  

Protein Based Vaccines

Rather than relying on your cells or their enzymes to make the viral proteins, protein based vaccines (sometimes called subunit vaccines) contain purified proteins (sometimes polysaccharides along with proteins).  As with viral vector vaccines and nucleic acid vaccines, the vaccine doesn't contain "live" components of the pathogen so there is no risk of introducing the disease.  While these types of vaccines seem straightforward in principle, it takes a lot of tweaking to elicit a robust enough immune response to establish immunological memory and often require a booster.  That being said, we have several subunit vaccines that are quite powerful tools in our vaccine arsenal (see list below).

One big advantage for protein based vaccines is that they are relatively inexpensive to produce and quite stable (compared to mRNA vaccines or viral vector vaccines), which make them a great tool in vaccinating people in countries that struggle with infrastructure or finding access to other, more expensive COVID-19 vaccines.  

Many existing and important vaccines are made this way, including:

  • Hepatitis B
  • Pertussis (Whooping cough)
  • Pneumococcal
  • Meningitis
  • Toxoid vaccines like: diphtheria, tetanus*** (process of production is different, but the biology of the response is the same)
  • Novavax COVID-19 vaccine (Emergency use approval in a few countries with applications for many more.  This US company plans to apply for approval in the US by the end of 2021)

Take a look at the figure below to see how the immune response is generated from each of these types of vaccines.

For full understanding, be able to answer:

  • Which strategies require host cell gene expression of microbe proteins?? Which do not?
  • Which likely illicit humoral adaptive immunity and which likely illicit cellular adaptive immunity?
  • The questions above require an understanding of which strategies present endogenous/intraceullar vs. extracellular antigens to the immune system for training. Once you ID this, you should be able to answer both questions above.
  • What are three things you learned?

    You MUST write these in your own words, do not copy & paste the same language.

  • What is one question you have after learning about immunity, vaccines and herd immunity?

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