FAQ: What types of vaccines exist for humans? (credit: Wikipedia)

Vaccines typically contain attenuated, inactivated or dead organisms or purified products derived from them. There are several types of vaccines in use.[38] These represent different strategies used to try to reduce the risk of illness while retaining the ability to induce a beneficial immune response.

• Attenuated

Main article: Attenuated vaccine

Some vaccines contain live, attenuated microorganisms. Many of these are active viruses that have been cultivated under conditions that disable their virulent properties, or that use closely related but less dangerous organisms to produce a broad immune response. Although most attenuated vaccines are viral, some are bacterial in nature. Examples include the viral diseases yellow fever, measles, mumps, and rubella, and the bacterial disease typhoid. The live Mycobacterium tuberculosis vaccine developed by Calmette and Guérin is not made of a contagious strain but contains a virulently modified strain called “BCG” used to elicit an immune response to the vaccine. The live attenuated vaccine containing strain Yersinia pestis EV is used for plague immunization. Attenuated vaccines have some advantages and disadvantages. Attenuated, or live, weakened, vaccines typically provoke more durable immunological responses. But they may not be safe for use in immunocompromised individuals, and on rare occasions mutate to a virulent form and cause disease.[39]

• Inactivated

Main article: Inactivated vaccine

Some vaccines contain inactivated, but previously virulent, micro-organisms that have been destroyed with chemicals, heat, or radiation[40] – “ghosts”, with intact but empty bacterial cell envelopes. They are considered an intermediate phase between the inactivated and attenuated vaccines.[41] Examples include IPV (polio vaccine), hepatitis A vaccine, rabies vaccine and most influenza vaccines.[42]

Avian flu vaccine development by reverse geneticstechniques

• Toxoid

Main article: Toxoid

Toxoid vaccines are made from inactivated toxic compounds that cause illness rather than the micro-organism.[43] Examples of toxoid-based vaccines include tetanus and diphtheria.[42] Not all toxoids are for micro-organisms; for example, Crotalus atroxtoxoid is used to vaccinate dogs against rattlesnake bites.[44]

• Subunit

Main article: Subunit vaccine

Rather than introducing an inactivated or attenuated micro-organism to an immune system (which would constitute a “whole-agent” vaccine), a subunit vaccine uses a fragment of it to create an immune response. One example is the subunit vaccine against hepatitis B, which is composed of only the surface proteins of the virus (previously extracted from the blood serum of chronically infected patients but now produced by recombination of the viral genes into yeast).[45] Another example is edible algae vaccines, such as the virus-like particle (VLP) vaccine against human papillomavirus (HPV), which is composed of the viral major capsid protein.[46] Another example is the hemagglutinin and neuraminidase subunits of the influenza virus.[42] A subunit vaccine is being used for plague immunization.[47]

• Conjugate

Main article: Conjugate vaccine

Certain bacteria have a polysaccharide outer coat that is poorly immunogenic. By linking these outer coats to proteins (e.g., toxins), the immune system can be led to recognize the polysaccharide as if it were a protein antigen. This approach is used in the Haemophilus influenzae type B vaccine.[48]

• Outer membrane vesicle

Outer membrane vesicles (OMVs) are naturally immunogenic and can be manipulated to produce potent vaccines. The best known OMV vaccines are those developed for serotype B meningococcal disease.[49][50]

• Heterotypic

Main article: Heterologous vaccine

Heterologous vaccines also known as “Jennerian vaccines”, are vaccines that are pathogens of other animals that either do not cause disease or cause mild disease in the organism being treated. The classic example is Jenner’s use of cowpox to protect against smallpox. A current example is the use of BCG vaccine made from Mycobacterium bovis to protect against tuberculosis.[51]

• Genetic vaccine

The subgroup of genetic vaccines encompass viral vector vaccines, RNA vaccines and DNA vaccines.

• Viral vector

Main article: Viral vector vaccine

Viral vector vaccines use a safe virus to insert pathogen genes in the body to produce specific antigens, such as surface proteins, to stimulate an immune response.[52][53]

• RNA

Main article: RNA vaccine

An mRNA vaccine (or RNA vaccine) is a novel type of vaccine which is composed of the nucleic acid RNA, packaged within a vector such as lipid nanoparticles.[54] Among the COVID-19 vaccines are a number of RNA vaccines under development to combat the COVID-19 pandemic and some have received emergency use authorization in some countries. For example, the Pfizer-BioNTech and Moderna mRNA vaccines have emergency use authorization in the US.[55][56][57]

• DNA

Main article: DNA vaccine

DNA vaccination – The proposed mechanism is the insertion and expression of viral or bacterial DNA in human or animal cells (enhanced by the use of electroporation), triggering immune system recognition. Some cells of the immune system that recognize the proteins expressed will mount an attack against these proteins and cells expressing them. Because these cells live for a very long time, if the pathogen that normally expresses these proteins is encountered at a later time, they will be attacked instantly by the immune system. One potential advantage of DNA vaccines is that they are very easy to produce and store.

In August 2021, Indian authorities gave emergency approval to ZyCoV-D. Developed by Cadila Healthcare, it is the first DNA vaccine approved for humans.

• Experimental

Electroporation system for experimental “DNA vaccine” delivery

Many innovative vaccines are also in development and use.

• Dendritic cell vaccines combine dendritic cells with antigens to present the antigens to the body’s white blood cells, thus stimulating an immune reaction. These vaccines have shown some positive preliminary results for treating brain tumors[58] and are also tested in malignant melanoma.[59]

• Recombinant vector – by combining the physiology of one micro-organism and the DNA of another, immunity can be created against diseases that have complex infection processes. An example is the RVSV-ZEBOV vaccine licensed to Merck that is being used in 2018 to combat ebola in Congo.[60]

• T-cell receptor peptide vaccines are under development for several diseases using models of Valley Fever, stomatitis, and atopic dermatitis. These peptides have been shown to modulate cytokine production and improve cell-mediated immunity.

• Targeting of identified bacterial proteins that are involved in complement inhibition would neutralize the key bacterial virulence mechanism.[61]

• The use of plasmids has been validated in preclinical studies as a protective vaccine strategy for cancer and infectious diseases. However, in human studies, this approach has failed to provide clinically relevant benefit. The overall efficacy of plasmid DNA immunization depends on increasing the plasmid’s immunogenicity while also correcting for factors involved in the specific activation of immune effector cells.[62]

• Bacterial vector – Similar in principle to viral vector vaccines, but using bacteria instead.[49]

• Antigen-presenting cell[49]

While most vaccines are created using inactivated or attenuated compounds from micro-organisms, synthetic vaccines are composed mainly or wholly of synthetic peptides, carbohydrates, or antigens.