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Viral Vaccine Immunology

by TheVaccineMom

What happens after you are injected with a viral vaccine? And which viral vaccine type is best?

(Note that I’m going to be talking about viral vaccines ONLY.)

First of all, there two basic types of viral vaccines: live attenuated vaccines (LAV) and inactivated (killed) vaccines.

LAV contain a vaccine virus that is a weakened version of the natural disease-causing virus. Inactivated vaccines use a killed version or a part(s) of the natural virus.

The body’s response to the vaccine virus in relation to the natural disease-causing virus has to do with the type of vaccine being administered, as well as how similar the vaccine virus is to the natural virus.

I’m going to go ahead and stop saying “vaccine virus”, and start calling this the “antigen”. An antigen is something foreign (in this case) that the body makes an immune response to, or something that’s the target for an immune response.

An inactivated vaccine contains all of the antigen needed to induce an immune response in the injected dose. Once it is injected into the muscle, the immune system begins to respond to this antigen. The LAV works a bit differently. There is only a very tiny amount of live weakened virus, and it must use the host body’s cells to reproduce in order to create the proper immune response. Once a LAV is injected into the muscle, the antigen migrates to the appropriate tissue in order to begin replication. The “appropriate tissue” in this case would be the tissue the natural virus would normally infect and replicate in.

Because the vaccine virus is so similar to the natural virus in LAV, these vaccines create an immune response virtually identical to the natural infection. The inactivated vaccine’s response is similar, yet one drawback is that immune stimulation occurs at the site of injection and not at the site of natural viral replication.

Some inactivated vaccines contain an adjuvant. An adjuvant is something added to the vaccine (most often an aluminum salt), and is used to help create a stronger immune response by activating the immune system or directing the antigen to the appropriate immune cells. If the vaccine has an adjuvant attached, the adjuvant dissociates and begins enhancing the “danger” signals already being picked up by the body’s first line of defense: the innate immune system.


Macrophages (Mφ) and dendritic cells (DC) are cells of the innate immune system that “see” this antigen first. These types of cells have special receptors that recognize antigen as non-self and thus, as danger to the body. With this danger comes the flooding of more of these cells, several other types of immune cells, and the generation of inflammation.

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The many Mφ recognize the antigens as foreign invaders and engulf them. Once inside, the antigen is chopped up into smaller pieces and then displayed on the Mφ surfaces. The Mφ send out signals to increase inflammation and bring leukocytes to the site of the antigen. Macrophages present the antigen pieces to the leukocytes.

For more on this: The beginning innate immune response to a microbe.

Remember I said LAV travel to the site of natural infection? This response and immune stimulation, including inflammation, would occur there. An inactivated vaccine response occurs at the injection site. This makes the site for non-live vaccines much more important than for live vaccines. Injection must be given in a place where patrolling DC are in larger quantities. Dendritic cells are always on patrol in the body, and found in especially high numbers in the vascularized muscle tissue. Therefore inactivated vaccines are injected into the muscle for greater immune response.

Once DC encounter the antigen, they can engulf it, undergo a brisk maturation, and then migrate through the lymphatic system to local lymph nodes. There, they encounter B and T  lymphocytes (B cells and T cells).

The DC are able to provide the T cells with antigen-specific “danger” signals (cell-mediated immunity). T cells subsequently become activated and CD4+ T helper (Th) cells send out growth factors and signals to generate B cell responses and CD8+ cytotoxic T lymphocytes (CTL) responses. CTL can kill viral infected cells and release anti-viral chemicals. The B cells proliferate and differentiate into antibody-secreting plasma cells or memory B cells. Antibody-secreting B cells release antibodies capable of binding that specific antigen (humoral immunity).

Most viral vaccine antigens trigger both B and T cell responses. B and T cells both remember this antigen for future invasion and quickly fight it off to keep you from getting sick.
Any other components of the vaccine, such as adjuvants, preservatives, chemicals used in the making of the vaccine, etc., are either used by the body or absorbed into the blood where they are excreted from the body via excrement or urine. Formaldehyde, a trace chemical used to inactivate viruses in the making of  some vaccines, is a chemical that the body actually can use in it’s everyday processes.
For more about formaldehyde in vaccines: The use of formaldehyde in vaccines.

So which type of vaccine creates the “best” response?

The response to a LAV is almost identical to the response the body would make to the natural virus. Research shows that the immune system cannot tell the difference between the two responses.3 LAV are also often effective with just one dose (except for the live oral vaccines).

Several doses are needed of inactivated vaccines to yield full protective immunity. The first dose “primes” the immune system. One or two more doses are needed before there is full protection. With this type of vaccine, it is also important to maintain the proper schedule when getting vaccinated. There must be a minimal time of 3 weeks between the primary dose and the following dose. This allows for successive waves of antigen-specific responses. Following those, you must wait 4 months before getting the following booster.  This allows for affinity maturation of memory B cells, which leads to a higher secondary responses. And antibody titers often wane over time, so boosters are needed to maintain protection with inactivated vaccines.

In comparison, LAV usually maintain a longer lasting antibody response. This is due to the persistence of antigen within the host.

Live attenuated vaccines are the current ideal vaccine type. They generate strong and long-lasting responses. The inactivated vaccines, though, when administered properly and following the correct time schedule, are also very powerful immune system stimulators and do offer a huge amount of protection from disease.

So what’s the best vaccine? The one that keeps you from getting sick! Go get vaccinated.


1. Siegrist, Claire-Anne. Vaccine Immunology. Elsevier Vaccine Immunology.  Link.

2.  World Health Organization. www.who.int

3. Immunisation Advisory Center. www.immune.org

4. Abbas, Abul K., Andrew H. Lichtman, and Shiv Pillai. Cellular and Molecular Immunology. Philadelphia: Saunders Elsevier, Inc., 2010.

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