Vaccinations

Definitions & Key takeaways

Vaccinations, also known as immunizations, are a way to protect individuals from infectious diseases. Vaccines work by stimulating the immune system to recognize and fight specific pathogens, such as viruses or bacteria. They allow us to develop active immunity where a protective adaptive immune response is made to pathogens without causing disease in the patient.

There are four main types of vaccines: Live attenuated, inactivated, subunit, and toxoid vaccines. Live attenuated and inactivated vaccines are whole-cell vaccines, which means that the whole virus or bacteria is used to create the vaccine. Subunit and toxoid vaccines are considered fractionated vaccines because only one part of the pathogen is used to create the vaccine. Vaccines are typically given through injections, nasal sprays, or oral doses, and are usually recommended for infants and young children, as well as for adults who may be at risk for certain infectious diseases. Some vaccines, such as the flu vaccine, need to be given annually, while others provide lifelong protection after a series of doses.

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When you get an infection, you develop adaptive immunity. In other words, you generate memory T and B cells, so that if you encounter the same antigen again, they can quickly replicate and respond.
Most of the time we think of immunologic memory developing after natural infection. But memory T and B cells also develop after vaccination.
Vaccination is the process of generating a protective adaptive immune responses against microbes by exposure to nonpathogenic forms or components of microbes.
That’s the key - getting long term active protection to a harmful microbe, from something that’s not harmful. Vaccination also helps up to establish herd immunity.
Herd immunity is the concept that if enough people in the population - or herd - are vaccinated the entire population, even those who are unvaccinated, develop a higher resistance to that infection.
The amount of people within a herd that need to be vaccinated to maintain herd immune status differs from pathogen to pathogen.
When too few people in a herd are vaccinated, there are more people in the population that are able to get the illness and spread it.
Vaccination is an active process of developing immunity. This is different from passive immunity which is where a person gets antibodies that are made by another person or animal like a horse or mouse or by cells in a lab.
A common form of this is when antibodies are pooled from the community and is given intravenously - it’s called intravenous immunoglobulin or IV-Ig.
Passive immunity last for only as long as the antibodies last - usually weeks to months. The antibodies that an infant receives from their mother in utero or during breastfeeding are examples of passive immunity.
IgG antibodies in the blood cross the placenta initially protecting the baby to some pathogens that mom has already made antibodies to.
These IgG maternal antibodies will be degraded around six months of age. IgA antibodies are plentiful in breast milk and are passed to the baby during nursing, these antibodies provide protection from pathogens that may be found at mucosal sites.
Once a baby weans off of breastmilk, these antibodies are no longer passed and the ones that have already entered the baby slowly degrade over the course of a few months.
Fortunately, by that point the baby will begin to make some of their own antibodies. Vaccines can be administered four ways: intramuscularly, intradermally, subcutaneously or subQ, or orally.
Typically, a vaccine is considered successful if it results in a strong antigen specific antibody titer, meaning in most recipients a strong antibody response is made to the vaccine.
When a patient receives a vaccine, CD4+ helper T cells are activated and produce cytokines like IFN gamma, TNF alpha, and IL-2 to promote growth of immune cells and class switching of activated B cells.
Once activated B cells will differentiate into plasma cells capable of producing IgG, IgA, or IgE antibodies. The exact antibody response depends on the route and type of vaccine.
For example, most intramuscular vaccinations lead to IgG production while the rotavirus vaccine, which is given orally, leads to IgA production.
There are four main types of vaccines: Live attenuated, inactivated, subunit, and toxoid vaccines. Live attenuated and inactivated vaccines are whole cell vaccines, which means that the whole virus or bacteria is used to create the vaccine.
Subunit vaccines - which includes polysaccharide vaccines, and Toxoid are considered fractionated vaccines because only one part of the pathogen is used to create the vaccine.
Live vaccines are attenuated, meaning that the pathogen has been weakened in the laboratory to make it less pathogenic, but still able to replicate in the vaccinated person so that it can stimulate an immune response.
In fact, the immune response to a live attenuated vaccine is almost identical to what happens in a natural infection. Live vaccines are used to protect against Measles, Mumps, Rubella, and Varicella - the MMR-V vaccine, Rotavirus, Smallpox, and Yellow fever.
Inactivated vaccines use a pathogen that has been killed using heat or chemical fixation with formalin. The immune response is mostly humoral or antibody mediated and with little to no cellular immunity, meaning mostly plasma cells making antibodies, and not T cells.
As a result, the immune response generated by inactivated vaccines is not as strong as that from natural infection or from a live vaccine.
For this reason, as immunity wanes over time patients may require “booster shots” or additional vaccination to boost the memory response.
Inactivated vaccines are used to protect against Hepatitis A, polio, rabies, and Influenza. Subunit vaccines that contain just the portions of pathogens that our bodies response to - like polysaccharides or proteins.
Often proteins from several different pathogens are conjugated or attached together to form conjugate subunit vaccines. These vaccines include the most immunogenic pieces of the pathogen - basically the antigens for that pathogen that most immune cells respond to.
For example - immune cells react strongly to the polysaccharides on Streptococcus pneumoniae, and that’s why the vaccine contains those polysaccharides.
The immune response to a polysaccharide vaccine is considered T cell independent because T cells can only respond to protein antigens, and not polysaccharides.
Polysaccharide vaccines are not very effective in children younger than 2 years of age. That’s because children under 2 seem to respond better when T cell help is available, because their immune systems are still immature and developing.
Basically the new B cells, need all the cytokine help they can get to make a strong antibody response. Also, without T cell help, even though B cells can turn into plasma cells and generate antibodies, they cannot turn into memory B cells, even in adults.
That means that repeated doses of polysaccharide vaccine are needed to maintain the immune response. Subunit and conjugate subunit vaccines protect us from Heamophilus influenza type B, Hepatitis B, human papillomavirus, Bordetella pertussis which causes pertussis or whooping cough, Streptococcus pneumoniae which can cause pneumonia, Neisseria meningitidis which causes meningitis, and varicella zoster virus which causes chickenpox and shingles.
Toxoid vaccines are vaccines specifically against toxins produced by pathogens like Clostridium tetani which makes tetanus toxin and Corynebacterium diptheriae which makes diphtheria toxin.
These toxins are typically the main cause of illness and can be deadly. A toxoid is formed when the toxin is fixed or inactivated, normally again using formalin, making it the same structure as the toxin but unable to cause disease.
Toxoid vaccines are often combined with subunit vaccines to make a more immunogenic or strong vaccine. For example the TDaP and DTaP vaccine provides coverage against the toxins for tetanus, diphtheria, and pertussis as well as the numerous non-toxin pertussis antigens like hemagglutinin, pertactin, and fimbriae which are all parts of the diphtheria bacterium, but not part of the toxin.
Conjugation increases the immunogenicity of the subunit as more cytokines will be present because of the peptide. In addition to conjugation, many vaccines use adjuvants, which is a molecule that further boosts the immune response.
Two common adjuvants are aluminum and monophosphoryl lipid A. Adjuvants can enhance the immune response in two ways.
First, they help an antigen remain in one location to enhance activation of antigen presenting cells. Second, when an adjuvant interacts with nearby antigen presenting cells, it makes them express higher levels of costimulatory molecules like B7, which are needed to activate T cells.
Now let’s go through some contraindications for vaccines. First and foremost, it’s best to get a vaccine when you’re healthy, so individuals who have a moderate or severe infection, and not just a mild infection like an upper respiratory tract infection, should wait until they recover before getting a vaccine.
Many vaccines, including the seasonal flu vaccine, are sometimes generated in chicken eggs, so patients who have allergies to chicken eggs or any other vaccine component should avoid those particular vaccines.
Likewise, if you have ever had an allergic reaction to a vaccine before or have developed Guillain-Barre Syndrome, a rare demyelinating condition of the lower motor tracts that is sometimes associated with infection you may need to avoid influenza vaccines, as well as DTaP.
Unfortunately, people with a weakened immune system, including pregnant women, cannot receive live attenuated vaccines because of the small risk that their immune system couldn’t handle even a weakened pathogen.
Those include the HPV vaccine as well as live vaccines like MMR, Meningococcal B, and Rotavirus. Lastly, vaccines have become controversial largely due to misinformation.
There is no link between vaccines and autism, and there’s no link between a vaccine preservative called thimerosal and mercury poisoning.
Nevertheless, to assuage parental concerns, in 2001 thimerosal was removed from childhood vaccines in the United States.
Today thimerosal is only used in some formulations of the influenza vaccine. Additionally, there’s no evidence that getting too many vaccines at one time overwhelms the immune system or that children cannot mount a robust immune response.
Finally, there’s no evidence that spacing out vaccines or only giving children some vaccines and not others is beneficial.
Quite the opposite - not protecting individuals, particularly children, for any period of time, with effective vaccines, leaves them vulnerable to diseases that can be severe or fatal.
Alright, as a quick recap vaccination is a form of active immunity where a protective adaptive immune response is made to a pathogen without causing disease in the patient.
There are four broad types: Live attenuated, inactivated, subunit/polysaccharide, and toxoid. Subunit and toxoid maybe conjugated together to boost the immune response to these pathogen components.
Additionally adjuvants may be used to increase the immune responses made to the pathogens. There’s a lot of misinformation about vaccines, but the science that supports them is overwhelming and clear.