How Vaccines Work and How Many Types?

Figure 1 Vaccines, PAMPs, and Adjuvants^[10]

What is Vaccine?

A vaccine 

• Is a biological preparation that provides active acquired immunity to a particular infectious disease
• Can be prophylactic or therapeutic
• Prophylactic
• Prevent or ameliorate the effects of a future infection by a natural or "wild" pathogen
• Therapeutic 
• Fight a disease that has already occurred, such as cancer
• Contains an agent that
• Stimulates the body's immune system to recognize the agent as a threat, destroy it, and to further recognize and destroy any of the microorganisms associated with that agent that it may encounter in the future. 
• Is often made from weakened or killed forms of the microbe, its toxins, or one of its surface proteins.

Virus Vaccine Types

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

• Live attenuated virus
• Whole killed virus
• Split virus
• Subunit vaccine
• Virus like particles
• Toxoid
• Recombinant subunit
• Conjugate
• Polysaccharide

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:

1. Isolation of a specific protein from a virus and administering this by itself
2. Recombinant subunit vaccine
• Involves putting an antigen's gene from the targeted virus or bacterium into another virus (virus vector), yeast (yeast vector), as in the case of the hepatitis B vaccine[3] or attenuated bacterium (bacterial vector) to make a recombinant virus or bacteria

How Vaccines Work?

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

• Antigen 
• Natural adjuvant 

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 

• HIV-1
• Through rapid in-host mutation and escape from antibody recognition
• Influenza virus
• Through antigenic drift to avoid previous season’s antibody recognition
• Herpes simplex virus 
• Through the expression of evasin molecules on virion surface that render antibodies useless

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

1. Gilead’s coronavirus drug: why experts are cautious on its prospects (ft.com)
2. A COVID-19 vaccine: 5 things that could go wrong
3. Covid-19 vaccine delivery faces problems, warns DHL
4. Moderna COVID-19 vaccine appears to work as well in older adults in early study
• Moderna said the immune responses in those aged between ages 56 and 70, above age 70 and those 18 to 55-years-old were similar
• Moderna has never brought a vaccine to market before
5. Iceland Has Very Good News About Coronavirus Immunity
6. Inhaled Vaccines Aim to Fight Coronavirus at Its Point of Attack
7. COVID-19 antibodies last at least three months; so do symptoms for many
8. Eli Lilly Virus Antibody Trial Paused Due to Safety Concerns
9. Characterizing COVID-19 antibodies for potential treatments
10. Why and How Vaccines Work