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Vaccine Immunology

Viral Vaccine Immunology

by TheVaccineMom
written 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.

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Laboratory LingoVaccine Terminology

Descendants of human fetal cells in the making of vaccines

by TheVaccineMom
written by TheVaccineMom

Are there fetal cells in vaccines? No. Do some vaccines contain viruses grown in cells from the human fetal origin? Yes. But, I feel this needs some explanation.

And before I get started, this isn’t meant to be a debate or opinion article. These are just the facts as I’ve researched them. And before I get into the issue at hand, you’re going to be getting a microbiology lesson…

The cell theory states: All cells arise from pre-existing cells.

Remember the term mitosis from biology class? That’s how parent cells make their daughter cells. The parent cell replicates all of their chromosomes into two sets and then splits into two cells, leaving one set of chromosomes in each cell. That’s it, in a nutshell. This happens over and over and over: parents forming daughters, and daughters becoming parents and forming more daughters.

Under the right conditions, cells love to reproduce. Scientists can take all kinds of cells and grow them in the laboratory under controlled conditions. Cells that are grown in an artificial environment, such as a culture dish, in a nutrient-rich solution to support the growth of the cells, and under controlled/ideal conditions of temperature, humidity, and gaseous atmosphere are called a cell culture.

Cells in a culture can be grown directly from living tissues. This is called primary cell culture. And oftentimes a primary cell culture will contain many types of cells in one dish.

These primary cultures can be manipulated in the lab until only one type of cell remains. Cell culture with only one type of cell is called a cell strain.

The cell strain is then used to establish a cell line. A cell line is a cell culture formed from a single cell, and thus, each cell in the culture will be daughters of that cell. That means each cell in the culture will have the exact same genetic makeup. This uniformity allows for experimental control.

Got it? Okay. Now, just focus on the cell line, daughters of just ONE CELL. Daughters becoming parents and making more daughters…

And a side note: Cells do not reproduce to infinity. There are a set number of times a cell can reproduce before it can no longer make daughter cells (called the Hayflick limit). So, scientists have to introduce a genetic mutation into cell lines that allow them to reproduce indefinitely, this is called an immortalized cell line.

Now we jump to virology. A virus lacks the ability to reproduce on its own. It needs to use a cell in order to make many, many copies of itself in order to cause disease. Therefore, to make a vaccine to create immunity to a virus, you must first have many copies of a virus, and to have many copies of a virus, you need cells to infect the virus with.

So, researchers infect cells with a virus to get more viruses to use in a vaccine. Okay. But, you can’t use the virus as is in the vaccine because it will lead to infection with the disease, so there has to be something done to the virus so that it cannot cause disease. A virus is unable to cause disease if it cannot make enough copies of itself to infect enough cells in the body. So, the best way to weaken, or attenuate a virus, is to make it so that it is unable to replicate in the body.

How do you do this?

A cell line is infected with a virus. Once the virus establishes itself and begins to reproduce in the cells, the conditions under which the cells are grown are slowly changed. This causes a mutation in the virus so that the virus grows best under the altered conditions. These are conditions that are different from those of the normal human body. We call this new virus an attenuated (weakened) virus.

The attenuated virus is the virus that can now be injected into the body as a live attenuated vaccine. The weakened virus provokes an immune response by the body but cannot replicate efficiently, so it is unable to cause disease. This type of vaccine elicits the most potent and long-lasting of all vaccine-related immune responses on the market today, requiring the fewest boosters.

On to the matter at hand: The cells used to make the cell lines.

There are two human cell strains used to create vaccines that are in use today. The cells used to grow the viruses for these vaccines are descendants of aborted fetal cells. And I want to stress the fact that NOT ALL vaccines use pathogens grown in human cell lines.

The first cell line, WI-38 (Winstar Institute 38), was developed by Leonard Hayflick in 1962. These cells are descendants of lung cells (human diploid lung fibroblasts) from a four-month-old female fetus aborted because the family felt they had too many children.6

Notice the phrase, “descendants of”. All of the cells in this cell line are daughters of one cell found in the lung tissue of a fetus, generations removed from the original cell.

The cell line, WI-38, was found to grow many viruses very well, including the rubella virus. The history and making of the rubella virus vaccine paints a great picture of how an attenuated viral vaccine is made using a human cell line:

The rubella virus was isolated by an unrelated physician, Stanley Plotkin, also working at Winstar Institute. Plotkin grew the rubella virus in the WI-38 cells at a much lower temperature [86°F (30°C)] than normal human temperature [98.6°F (37°C)]. This created a rubella virus that grew best at lower than normal temperature, and that grew very poorly at normal body temperature. After 25 growth cycles of cells in culture, the virus was considered unable to reproduce efficiently and cause disease in a human. It could still, however, evoke quite the immune response and leave the body with powerful memory antibodies to the rubella virus.

This rubella vaccine is still used in the United States today.

The following are the vaccines created using WI-38 cells:

 Live vaccines against rubella2:

  • the monovalent vaccines against rubella Meruvax® (Merck), Rudivax® (Sanofi Pasteur, Fr.), and Ervevax® (RA 27/3) (GlaxoSmithKline, Belgium)
  • the combined vaccine MR against rubella and measles, M-R-VAX® (Merck, US) and Rudi-Rouvax® (AVP, France)
  • the combined vaccine against rubella and mumps, marketed under the name of Biavax® (Merck, U.S.)
  • the combined vaccine MMR (measles, mumps, rubella) against measles, mumps, and rubella, marketed under the name of M-M-R® II (Merck, US), R.O.R.®, Trimovax® (Sanofi Pasteur, Fr.), and Priorix® (GlaxoSmithKline UK).

Other vaccines2:

  • A vaccine against chickenpox, Varivax®, produced by Merck (using WI-38 and MRC-5 cell lines)

The second human cell line used to grow viruses in for vaccines is called MRC-5 (Medical Research Council 5), developed by J.P Jacobs in 1966.5 This cell line is also a descendant of a human lung fibroblast. The cells came from a 14-week male fetus aborted for “psychiatric reasons” from a 27-year-old woman in the UK.

The vaccines produced with viruses grown in MRC-5 cells include:

  • two vaccines against hepatitis A, one produced by Merck (VAQTA), the other one produced by GlaxoSmithKline (HAVRIX)
  • one vaccine against chickenpox, Varivax®, produced by Merck (using WI-38 and MRC-5)
  • one inactivated poliovirus vaccine Poliovax® (Aventis-Pasteur, Fr.)
  • one vaccine against rabies, Imovax®,
  • one vaccine against smallpox, AC AM 1000 (still on trial)

The WI-38 and MRC-5 cell lines are the only two human cell lines used in the making of vaccines.

Some things to note:

  • These cell lines began using fetal cells aborted over 50 years ago, and since then, the cell lines have grown independently.
  • Neither abortion used for the creation of these cell lines was performed for the purpose of vaccine development. They were done so by maternal choice.
  • Not all vaccines are made using viruses grown in cells with a human fetal origin.
  • Fetal cells are not contained in vaccines.

Resources:

  1. “Human Cell Strains in Vaccine Development”. The history of vaccines. The College of Physicians of Philadelphia. 31 July 2014.
  2. Sgreccia, E. Moral Reflections On Vaccines Prepared from Cells Derived From Aborted Human Foetuses. 9 June 2005. A letter found under Immunization Action Coalition’s “Vaccine Concerns”. www.immunize.org/concerns.
  3. Plotkin. “History of Vaccination.” Pnas. 5 Febuary 2014. Vol. 111, no. 34, pp. 12283-12287.
  4. Sven, G., S. Plotkin, K. McCarthy. “Gamma Globulin Prophylaxis; Inactivated Rubella Virus; Production and Biological Control of Live Attenuated Rubella Virus Vaccines”. American Journal of Diseases of Children. August 1969. vol. 118, no. 2, pp. 372-381.
  5. Jacobs, J.P., C.M. Jones, J.P. Bailie. “Characteristics of a Human Diploid Cell Designated MRC-5”. Nature. 11 July 1970. vol. 277, pp.168-170.
  6. Wadman, M. “Medical Research: Cell Division.” 27 June 2013. Vol. 498. Pp 422-426.
  7. Plotkin, S., D. Cornfield, and T. Ingalls. “Studies of Immunization With Living Rubella Virus.” Amer J Dis Child. October 1965. Vol. 110. Pp. 381-389.
  8. “First Step Towards Vaccine for Hepatitis A.” The New Scientist. 31 May 1979. Vol. 82. No. 1157. p. 730.
  9. Nunnally, B.K., V.E. Turula, and R.D. Sitrin. Vaccine Analysis: Strategies, Principles, and Control. 27 November 2014. pp. 54-57.
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