Vaccinations

When you get an infection, you develop adaptive immunity. In other words, you generate memory T and B cells, so 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 can also develop after vaccination. Vaccination is the process of generating a protective adaptive immune response against microbes by exposure to nonpathogenic forms or components of microbes. And that’s the key - getting long-term active protection to a harmful microbe, from something that’s not harmful.

Vaccination also helps to establish herd immunity. Herd immunity is the concept that if enough people in the population - or herd - are vaccinated, then the entire population, even those who are unvaccinated, is less likely to get that infection. This is because the disease has a much lower chance of spreading to unvaccinated individuals when herd immunity is established. The percentage of people within a herd that need to be vaccinated to maintain herd immune status varies depending on the 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 then spread it to others.

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 passive immunity is when antibodies are pooled from human donors and are given intravenously - called intravenous immunoglobulin or IVIG. Passive immunity lasts 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 other examples of passive immunity. IgG antibodies in the blood cross the placenta, initially protecting the baby from some of the pathogens that mom has already made antibodies to. These maternal IgG antibodies will be degraded around six months of age. IgA antibodies are plentiful in breast milk and are passed to the baby during breastfeeding. These antibodies provide protection from pathogens that may be found at mucosal sites. Once a baby weans off breastmilk, these IgA antibodies are no longer present.

Vaccines can be administered five different ways: intramuscularly, intradermally, subcutaneously, intranasally, or orally. Typically, a vaccine is considered successful if it results in a strong antigen-specific antibody titer, meaning that most recipients generate a strong antibody response to the vaccine. Other determinants of a successful vaccine are a strong cellular immunity response, and the vaccine’s overall effectiveness at preventing disease.

When a patient receives a vaccine, CD4+ helper T cells are activated and produce cytokines like IFN gamma, IL-4 and IL-2 to promote growth of immune cells and class switching of activated B cells. Once activated, B cells will first differentiate into plasma cells that produce IgM antibodies, followed by class switching to produce other antibody types such as IgG or IgA. 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 five main types of vaccines: Live attenuated, inactivated, subunit, toxoid, and messenger ribonucleic acid, or mRNA, 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. Finally, mRNA vaccines are a type of nucleic acid vaccine, where genetic instructions are delivered to host cells so they can produce pathogen proteins that trigger an immune response.

Live vaccines are attenuated, meaning 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; as well as 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, with strong activation of plasma cells to make antibodies, and less cellular immunity - meaning, less T cell response. As a result, the immunity generated by inactivated vaccines is not as robust as that from natural infection or from a live vaccine. Because immunity can wane over time, patients may require “booster shots” or additional doses of the vaccine to maintain protection. Inactivated vaccines are used to protect against hepatitis A, polio, rabies, and influenza.

Subunit vaccines contain only the portions of pathogens that our bodies respond to - such as polysaccharides or proteins. 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.