How Vaccines Work and 

How Many Types?

What is Vaccine?

A vaccine 

Figure 1 Vaccines, PAMPs, and Adjuvants[10] 

Virus Vaccine Types

In this article, we will focus on virus vaccines only.  Its various vaccine types include (see Figure 1):

A subunit vaccine presents an antigen to the immune system without introducing viral particles, whole or otherwise.  There are two methods of making a subunit vaccine:

How Vaccines Work?

Live-attenuated (and to some degree, inactivated) vaccines have worked because they provide the two requisite signals to induce immunity:

But, immunization using toxoid alone induced poor immunity. #GastonRamon found that toxoid injected with ‘stuff’ (or adjuvant; see Figure 2) including tapioca, lecithin, agar, starch oil, saponin or breadcrumbs improved immunity.

Figure 2 Timeline of Adjuvant Used in Human Vaccines[10] 

New Approaches and New Types

In 1986, the first genetically engineered vaccine—the Hepatitis B surface antigen recombinant vaccine—became available

Until the last couple of decades, vaccines were developed using empirical approaches.  More recently, in parallel with increasing availability of sequencing and bioinformatics tools, there has been an increased focus on so-called “rational” vaccine design approaches.

Antibody-Dependent Immunity vs Cell-Mediated Immunity 

Antibody-Dependent Immunity

Antibodies are the focus of almost all vaccines, and currently levels of antibodies raised against the vaccine antigens are used as correlates of protection.

Cell-Mediated Vaccines 

Not all viruses are amenable to antibody-dependent immunity. Some viruses have circumvented the ability of antibodies to control them, including 

Fortunately, there are conserved epitopes that can be used to generate T cell immunity (or cell-mediated immunity) through vaccines. 

Neutralizing Antibody

An individual can produce hundreds or thousands of different variants of antibodies against any pathogen or foreign substance, including viruses, leading to a wide diversity of antibodies in a single person and in the human population. Some antibodies are better at blocking a virus than others. 

When an antibody effectively renders a virus unable to infect cells—knocking it out, so to speak—it is called "neutralizing."

"An ideal treatment would be a combination or 'cocktail' of different antibodies that attack the virus in different, but still effective, ways," says Christopher Barnes.[9] "With a combination of antibodies, it's less likely that a virus can evolve to escape them."

T Cell Immunity

A key aspect of T cell immunity is that it works best if the T cells are already present at the site of entry, i.e., the mucosal surface. However, vaccines injected into muscle often fail to induce mucosa-resident memory T cells. 

A two-step vaccine strategy, prime and pull, can overcome this distribution problem by recruiting and establishing tissue-resident memory T cells in a tissue of choice (primary route of viral entry) using chemokines or chemokine-inducing agents (Iwasaki, 2016). 

T cell-based vaccines hold promise for antibody-evasive pathogens and cancer vaccines in which no surface antigens can be targeted.

References